changeset 0:e545d0a25ffe draft

Uploaded

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/README.md	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,1 @@
+vep

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/.hgignore	Mon Jul 15 05:17:17 2019 -0400
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+syntax: glob
+*~

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/AncestralAllele.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,281 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+
+=cut
+
+=head1 NAME
+
+ AncestralAllele
+
+=head1 SYNOPSIS
+
+ mv AncestralAllele.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin AncestralAllele,homo_sapiens_ancestor_GRCh38_e86.fa.gz
+
+=head1 DESCRIPTION
+
+ A VEP plugin that retrieves ancestral allele sequences from a FASTA file.
+
+ Ensembl produces FASTA file dumps of the ancestral sequences of key species.
+ They are available from ftp://ftp.ensembl.org/pub/current_fasta/ancestral_alleles/
+
+ For optimal retrieval speed, you should pre-process the FASTA files into a single
+ bgzipped file that can be accessed via Bio::DB::HTS::Faidx (installed by VEP's
+ INSTALL.pl):
+
+ wget ftp://ftp.ensembl.org/pub/release-90/fasta/ancestral_alleles/homo_sapiens_ancestor_GRCh38_e86.tar.gz
+ tar xfz homo_sapiens_ancestor_GRCh38_e86.tar.gz
+ cat homo_sapiens_ancestor_GRCh38_e86/*.fa | bgzip -c > homo_sapiens_ancestor_GRCh38_e86.fa.gz
+ rm -rf homo_sapiens_ancestor_GRCh38_e86/ homo_sapiens_ancestor_GRCh38_e86.tar.gz
+ ./vep -i variations.vcf --plugin AncestralAllele,homo_sapiens_ancestor_GRCh38_e86.fa.gz
+
+ The plugin is also compatible with Bio::DB::Fasta and an uncompressed FASTA file.
+
+ Note the first time you run the plugin with a newly generated FASTA file it will
+ spend some time indexing the file. DO NOT INTERRUPT THIS PROCESS, particularly
+ if you do not have Bio::DB::HTS installed.
+
+ Special cases:
+   "-" represents an insertion
+   "?" indicates the chromosome could not be looked up in the FASTA
+
+=cut
+
+package AncestralAllele;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+our $CAN_USE_FAIDX;
+our $DEBUG = 0;
+
+BEGIN {
+  if (eval { require Bio::DB::HTS::Faidx; 1 }) {
+    $CAN_USE_FAIDX = 1;
+  }
+}
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+
+  # get file
+  my $fasta_file = $self->params->[0] || "";
+  die("ERROR: Ancestral FASTA file $fasta_file not provided or found\n") unless $fasta_file && -e $fasta_file;
+  $self->fasta_file($fasta_file);
+
+  # get type of index we're creating/using
+  my $type = $fasta_file =~ /\.gz$/ ? 'Bio::DB::HTS::Faidx' : 'Bio::DB::Fasta';
+  die("ERROR: Bio::DB::HTS required to access compressed FASTA file $fasta_file\n") if $type eq 'Bio::DB::HTS::Faidx' && !$CAN_USE_FAIDX;
+  $self->index_type($type);
+
+  # init DB here so indexing doesn't happen at some point in the middle of VEP run
+  $self->fasta_db;
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Feature','Intergenic'];
+}
+
+sub get_header_info {
+  return { AA => 'Ancestral allele from '.$_[0]->fasta_file }
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  my $vf = $tva->variation_feature;
+
+  my ($start, $end) = ($vf->{start}, $vf->{end});
+
+  # cache AA on VF, prevents repeat lookups for multiple TVAs
+  if(!exists($vf->{_vep_plugin_AncestralAllele})) {
+
+    # insertion
+    return { AA => $vf->{_vep_plugin_AncestralAllele} = '-' } if $start > $end;
+
+    my $sr_name = $self->get_sr_name($vf->{chr});
+
+    # chr not in FASTA
+    return { AA => $vf->{_vep_plugin_AncestralAllele} = '?' } unless $sr_name;
+
+    my $fasta_db = $self->fasta_db;
+    my $type = $self->index_type;
+    my ($seq, $length);
+
+    if($type eq 'Bio::DB::HTS::Faidx') {
+      my $location_string = $sr_name.":".$start."-".$end ;
+      ($seq, $length) = $fasta_db->get_sequence($location_string);
+    }
+    elsif($type eq 'Bio::DB::Fasta') {
+      $seq = $fasta_db->seq($sr_name, $start => $end);
+    }
+    else {
+      throw("ERROR: Don't know how to fetch sequence from a ".ref($fasta_db)."\n");
+    }
+
+    reverse_comp(\$seq) if $vf->{strand} < 0;
+
+    $vf->{_vep_plugin_AncestralAllele} = $seq;
+  }
+
+  return { AA => $vf->{_vep_plugin_AncestralAllele} };
+}
+
+# getter/setter for fasta file path
+sub fasta_file {
+  my $self = shift;
+  $self->{_fasta_file} = shift if @_;
+  return $self->{_fasta_file};
+}
+
+# getter/setter for fasta index type
+sub index_type {
+  my $self = shift;
+  $self->{_index_type} = shift if @_;
+  return $self->{_index_type};
+}
+
+## CRIBBED FROM Bio::EnsEMBL::Variation::Utils::FastaSequence
+## MOVE THIS CODE TO SHARED UTILS SPACE?
+# creates the FASTA DB object
+# returns either a Bio::DB::Fasta or a Bio::DB::HTS::Faidx
+# uses a lock file to avoid partial indexes getting used
+sub fasta_db {
+  my $self = shift;
+
+  # if we've forked we need to re-connect
+  # but make sure we only do this once per fork
+  my $prev_pid = $self->{_prev_pid} ||= $$;
+  if($prev_pid ne $$) {
+    delete $self->{_fasta_db};
+    $self->{_prev_pid} = $$;
+  }
+
+  if(!exists($self->{_fasta_db})) {
+    my $fasta = $self->fasta_file;
+    my $type = $self->index_type;
+
+    # check lock file
+    my $lock_file = $fasta;
+    $lock_file .= -d $fasta ? '/.vep.lock' : '.vep.lock';
+
+    # lock file exists, indexing failed
+    if(-e $lock_file) {
+      print STDERR "Lock file found, removing to allow re-indexing\n" if $DEBUG;
+      for(qw(.fai .index .gzi /directory.index /directory.fai .vep.lock)) {
+        unlink($fasta.$_) if -e $fasta.$_;
+      }
+    }
+
+    my $index_exists = 0;
+
+    for my $fn(map {$fasta.$_} qw(.fai .index .gzi /directory.index /directory.fai)) {
+      if(-e $fn) {
+        $index_exists = 1;
+        last;
+      }
+    }
+
+    # create lock file
+    unless($index_exists) {
+      open LOCK, ">$lock_file" or throw("ERROR: Could not write to FASTA lock file $lock_file\n");
+      print LOCK "1\n";
+      close LOCK;
+      print STDERR "Indexing $fasta\n" if $DEBUG;
+    }
+
+    # run indexing
+    my $fasta_db;
+    if($type eq 'Bio::DB::HTS::Faidx' && $CAN_USE_FAIDX) {
+      $fasta_db = Bio::DB::HTS::Faidx->new($fasta);
+    }
+    elsif(!$type || $type eq 'Bio::DB::Fasta') {
+      $fasta_db = Bio::DB::Fasta->new($fasta);
+    }
+    else {
+      throw("ERROR: Don't know how to index with type $type\n");
+    }
+    print STDERR "Finished indexing\n" if $DEBUG;
+
+    throw("ERROR: Unable to create FASTA DB\n") unless $fasta_db;
+
+    # remove lock file
+    unlink($lock_file) unless $index_exists;
+
+    $self->{_fasta_db} = $fasta_db;
+  }
+
+  return $self->{_fasta_db};
+}
+
+# gets seq region name as it appears in the FASTA
+# the file contains names like "ANCESTOR_for_chromosome:GRCh38:10:1:133797422:1"
+# so want to map from "10" or "chr10" to "ANCESTOR_for_chromosome:GRCh38:10:1:133797422:1"
+sub get_sr_name {
+  my $self = shift;
+  my $sr_name = shift;
+
+  my $map = $self->fasta_name_map;
+  my $fasta_db = $self->fasta_db;
+
+  unless($map->{$sr_name}) {
+    foreach my $alt(
+      $sr_name =~ /^chr/i ? (substr($sr_name, 3)) : ('chr'.$sr_name, 'CHR'.$sr_name)
+    ) {
+      if($map->{$alt}) {
+        print STDERR "USING SYNONYM $alt FOR $sr_name\n" if $DEBUG;
+        $sr_name = $alt;
+        last;
+      }
+    }
+  }
+
+  return $map->{$sr_name} || undef;
+}
+
+sub fasta_name_map {
+  my ($self, $chr) = @_;
+
+  if(!exists($self->{_name_map})) {
+    my $fasta_db = $self->fasta_db;
+
+    my %map = map {(split(':', $_))[2] => $_}
+      $fasta_db->isa('Bio::DB::Fasta') ?
+      (grep {$_ !~ /^\_\_/} $fasta_db->get_all_primary_ids) :
+      ($fasta_db->get_all_sequence_ids);
+
+    $self->{_name_map} = \%map;
+  }
+
+  return $self->{_name_map};
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/Blosum62.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,125 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ Blosum62
+
+=head1 SYNOPSIS
+
+ mv Blosum62.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin Blosum62
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+ looks up the BLOSUM 62 substitution matrix score for the reference
+ and alternative amino acids predicted for a missense mutation. It adds
+ one new entry to the VEP's Extra column, BLOSUM62 which is the 
+ associated score. 
+
+=cut
+
+package Blosum62;
+
+use strict;
+use warnings;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+my @BLOSUM_62 = qw(
+ 4 -1 -2 -2  0 -1 -1  0 -2 -1 -1 -1 -1 -2 -1  1  0 -3 -2  0 
+-1  5  0 -2 -3  1  0 -2  0 -3 -2  2 -1 -3 -2 -1 -1 -3 -2 -3
+-2  0  6  1 -3  0  0  0  1 -3 -3  0 -2 -3 -2  1  0 -4 -2 -3
+-2 -2  1  6 -3  0  2 -1 -1 -3 -4 -1 -3 -3 -1  0 -1 -4 -3 -3
+ 0 -3 -3 -3  9 -3 -4 -3 -3 -1 -1 -3 -1 -2 -3 -1 -1 -2 -2 -1
+-1  1  0  0 -3  5  2 -2  0 -3 -2  1  0 -3 -1  0 -1 -2 -1 -2
+-1  0  0  2 -4  2  5 -2  0 -3 -3  1 -2 -3 -1  0 -1 -3 -2 -2
+ 0 -2  0 -1 -3 -2 -2  6 -2 -4 -4 -2 -3 -3 -2  0 -2 -2 -3 -3 
+-2  0  1 -1 -3  0  0 -2  8 -3 -3 -1 -2 -1 -2 -1 -2 -2  2 -3
+-1 -3 -3 -3 -1 -3 -3 -4 -3  4  2 -3  1  0 -3 -2 -1 -3 -1  3
+-1 -2 -3 -4 -1 -2 -3 -4 -3  2  4 -2  2  0 -3 -2 -1 -2 -1  1
+-1  2  0 -1 -3  1  1 -2 -1 -3 -2  5 -1 -3 -1  0 -1 -3 -2 -2 
+-1 -1 -2 -3 -1  0 -2 -3 -2  1  2 -1  5  0 -2 -1 -1 -1 -1  1
+-2 -3 -3 -3 -2 -3 -3 -3 -1  0  0 -3  0  6 -4 -2 -2  1  3 -1
+-1 -2 -2 -1 -3 -1 -1 -2 -2 -3 -3 -1 -2 -4  7 -1 -1 -4 -3 -2
+ 1 -1  1  0 -1  0  0  0 -1 -2 -2  0 -1 -2 -1  4  1 -3 -2 -2
+ 0 -1  0 -1 -1 -1 -1 -2 -2 -1 -1 -1 -1 -2 -1  1  5 -2 -2  0
+-3 -3 -4 -4 -2 -2 -3 -2 -2 -3 -2 -3 -1  1 -4 -3 -2 11  2 -3
+-2 -2 -2 -3 -2 -1 -2 -3  2 -1 -1 -2 -1  3 -3 -2 -2  2  7 -1
+ 0 -3 -3 -3 -1 -2 -2 -3 -3  3  1 -2  1 -1 -2 -2  0 -3 -1  4
+);
+
+my @AAs = qw(A R N D C Q E G H I L K M F P S T W Y V);
+
+sub new {
+    my $class = shift;
+
+    my $self = $class->SUPER::new(@_);
+
+    # construct a hash representing the matrix for quick lookups
+
+    my $num = @AAs;
+
+    for (my $i = 0; $i < $num; $i++) {
+        for (my $j = 0; $j < $num; $j++) {
+            $self->{matrix}->{$AAs[$i]}->{$AAs[$j]} = $BLOSUM_62[($i * $num) + $j];
+        }
+    }
+
+    return $self;
+}
+
+sub version {
+    return '2.3';
+}
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub get_header_info {
+    return {
+        BLOSUM62 => "BLOSUM62 substitution score for the reference and alternative amino acids",
+    };
+}
+
+sub run {
+    my ($self, $tva) = @_;
+
+    if ($tva->pep_allele_string && $tva->pep_allele_string =~ /^([A-Z])\/([A-Z])$/) {
+        
+        my $score = $self->{matrix}->{$1}->{$2};
+        
+        if (defined $score) {
+            return {
+                BLOSUM62 => $score
+            };
+        }
+    }
+
+    return {};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/CADD.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,137 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ CADD
+
+=head1 SYNOPSIS
+
+ mv CADD.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin CADD,whole_genome_SNVs.tsv.gz,InDels.tsv.gz
+
+=head1 DESCRIPTION
+
+ A VEP plugin that retrieves CADD scores for variants from one or more
+ tabix-indexed CADD data files.
+ 
+ Please cite the CADD publication alongside the VEP if you use this resource:
+ http://www.ncbi.nlm.nih.gov/pubmed/24487276
+ 
+ The tabix utility must be installed in your path to use this plugin. The CADD
+ data files can be downloaded from
+ http://cadd.gs.washington.edu/download
+ 
+=cut
+
+package CADD;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+
+  $self->expand_left(0);
+  $self->expand_right(0);
+
+  $self->get_user_params();
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Feature','Intergenic'];
+}
+
+sub get_header_info {
+  my $self = shift;
+  return {
+    CADD_PHRED => 'PHRED-like scaled CADD score',
+    CADD_RAW   => 'Raw CADD score'
+  }
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  my $vf = $tva->variation_feature;
+  
+  # get allele, reverse comp if needed
+  my $allele = $tva->variation_feature_seq;
+  reverse_comp(\$allele) if $vf->{strand} < 0;
+  
+  return {} unless $allele =~ /^[ACGT-]+$/;
+
+  my ($res) = grep {
+    $_->{alt}   eq $allele &&
+    $_->{start} eq $vf->{start} &&
+    $_->{end}   eq $vf->{end}
+  } @{$self->get_data($vf->{chr}, $vf->{start} - 2, $vf->{end})};
+
+  return $res ? $res->{result} : {};
+}
+
+sub parse_data {
+  my ($self, $line) = @_;
+
+  my ($c, $s, $ref, $alt, $raw, $phred) = split /\t/, $line;
+
+  # do VCF-like coord adjustment for mismatched subs
+  my $e = ($s + length($ref)) - 1;
+  if(length($alt) != length($ref)) {
+    $s++;
+    $ref = substr($ref, 1);
+    $alt = substr($alt, 1);
+    $ref ||= '-';
+    $alt ||= '-';
+  }
+
+  return {
+    alt => $alt,
+    start => $s,
+    end => $e,
+    result => {
+      CADD_RAW   => $raw,
+      CADD_PHRED => $phred
+    }
+  };
+}
+
+sub get_start {
+  return $_[1]->{start};
+}
+
+sub get_end {
+  return $_[1]->{end};
+}
+
+1;
\ No newline at end of file

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/CCDSFilter.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,62 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ CCDSFilter
+
+=head1 SYNOPSIS
+
+ mv CCDSFilter.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin CCDSFilter
+
+=head1 DESCRIPTION
+
+ A simple VEP filter plugin that limits output to variants that
+ fall in transcripts which have CCDS coding sequences.
+
+=cut
+
+package CCDSFilter;
+
+use strict;
+use warnings;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepFilterPlugin);
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub include_line {
+    my ($self, $tva) = @_;
+
+    my $t = $tva->transcript;
+
+    my @entries = grep {$_->database eq 'CCDS'} @{$t->get_all_DBEntries};
+   
+    return scalar @entries;
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/CSN.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,122 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+  CSN
+
+=head1 SYNOPSIS
+
+  mv CSN.pm ~/.vep/Plugins
+  ./vep -i variations.vcf --cache --plugin CSN
+
+=head1 DESCRIPTION
+
+  This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+  reports Clinical Sequencing Nomenclature (CSN) for variants.
+
+  Each notation is given with reference to the transcript identifier;
+  specify "--plugin CSN,1" to remove this identifier from the CSN string.
+
+  You may also wish to specify "--no_escape" to prevent the "=" in "p.="
+  notations being converted to the URI-escaped equivalent "p.%3D"; doing
+  so may break parsers looking for "=" as a KEY=VALUE separator.
+
+  See http://biorxiv.org/content/early/2015/03/21/016808.1
+
+=cut
+
+package CSN;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+use Bio::EnsEMBL::Variation::DBSQL::TranscriptVariationAdaptor;
+use Bio::EnsEMBL::Variation::DBSQL::DBAdaptor;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+  
+  # check config is OK
+  
+  # FASTA file defined, optimal
+  if(!defined($self->{config}->{fasta})) {
+    
+    # offline mode won't work without FASTA
+    die("ERROR: Cannot generate CSN without either a FASTA file (--fasta) or a database connection (--cache or --database)\n") if defined($self->{config}->{offline}) and !defined($self->{config}->{quiet});
+    
+    # cache mode will work, but DB will be accessed
+    warn("WARNING: Database will be accessed using this plugin; use a FASTA file (--fasta) for optimal performance") if defined($self->{config}->{cache}) and !defined($self->{config}->{quiet});
+  }
+  
+  no warnings 'once';
+  $Bio::EnsEMBL::Variation::DBSQL::TranscriptVariationAdaptor::DEFAULT_SHIFT_HGVS_VARIANTS_3PRIME = 1;
+  no warnings 'once';
+  $Bio::EnsEMBL::Variation::DBSQL::DBAdaptor::DEFAULT_SHIFT_HGVS_VARIANTS_3PRIME = 1;
+  
+  $self->{remove_transcript_ID} = $self->params->[0];
+  
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub variant_feature_types {
+  return ['VariationFeature'];
+}
+
+sub get_header_info {
+  return { CSN => 'Clinical Sequencing Nomenclature'};
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  my ($hgvs_c, $hgvs_p) = ($tva->hgvs_transcript || '', $tva->hgvs_protein || '');
+  
+  return {} unless $hgvs_c;
+  
+  # trim off transcript/protein ID
+  $hgvs_c =~ s/.+\:// if $self->{remove_transcript_ID}; 
+  $hgvs_p =~ s/.+\://;
+  
+  # change Ter to X
+  $hgvs_p =~ s/Ter/X/g;
+  
+  # leave just p.=
+  $hgvs_p = 'p.=' if $hgvs_p =~ /p\.\=/;
+  
+  # escape
+  $hgvs_p =~ s/\=/\%3D/g unless $self->{config}->{no_escape};
+  
+  return { CSN => $hgvs_c.($hgvs_p ? '_'.$hgvs_p : '') };
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/Carol.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,177 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ Carol
+
+=head1 SYNOPSIS
+
+ mv Carol.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin Carol
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that calculates
+ the Combined Annotation scoRing toOL (CAROL) score (1) for a missense mutation 
+ based on the pre-calculated SIFT (2) and PolyPhen-2 (3) scores from the Ensembl 
+ API (4). It adds one new entry class to the VEP's Extra column, CAROL which is
+ the calculated CAROL score. Note that this module is a perl reimplementation of 
+ the original R script, available at:
+
+ http://www.sanger.ac.uk/resources/software/carol/
+
+ I believe that both versions implement the same algorithm, but if there are any
+ discrepancies the R version should be treated as the reference implementation. 
+ Bug reports are welcome.
+
+ References:
+
+ (1) Lopes MC, Joyce C, Ritchie GRS, John SL, Cunningham F, Asimit J, Zeggini E. 
+     A combined functional annotation score for non-synonymous variants
+     Human Heredity (in press)
+
+ (2) Kumar P, Henikoff S, Ng PC.
+     Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm
+     Nature Protocols 4(8):1073-1081 (2009)
+     doi:10.1038/nprot.2009.86
+ 
+ (3) Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. 
+     A method and server for predicting damaging missense mutations
+     Nature Methods 7(4):248-249 (2010)
+     doi:10.1038/nmeth0410-248
+ 
+ (4) Flicek P, et al.
+     Ensembl 2012
+     Nucleic Acids Research (2011)
+     doi: 10.1093/nar/gkr991
+
+=cut
+
+package Carol;
+
+use strict;
+use warnings;
+
+use Math::CDF qw(pnorm qnorm);
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+my $CAROL_CUTOFF = 0.98;
+
+sub version {
+    return '2.3';
+}
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub get_header_info {
+    return {
+        CAROL => "Combined Annotation scoRing toOL prediction",
+    };
+}
+
+sub run {
+    my ($self, $tva) = @_;
+    
+    my $pph_pred    = $tva->polyphen_prediction;
+    my $pph_score   = $pph_pred ? ($pph_pred eq 'unknown' ? undef: $tva->polyphen_score) : undef;
+    my $sift_score  = $tva->sift_score;
+
+    my ($carol_pred, $carol_score) = compute_carol($pph_score, $sift_score);
+    
+    my $results = {};
+
+    if (defined $carol_pred) {
+
+        $carol_score = sprintf "%.3f", $carol_score;
+
+        my $result = "$carol_pred($carol_score)";
+
+        if (@{ $self->params } > 0) {
+            $result = $carol_pred if ($self->params->[0] =~ /^p/i);
+            $result = $carol_score if ($self->params->[0] =~ /^s/i);
+        }
+
+        $results = {
+            CAROL => $result,
+        };
+    }
+    
+    return $results;
+}
+
+sub compute_carol {
+
+    my ($pph_score, $sift_score) = @_;
+    
+    my $carol_score;
+
+    if (defined $pph_score) {
+        $pph_score = 0.999 if $pph_score == 1;
+        $pph_score = 0.0001 if $pph_score == 0;
+    }
+
+    if (defined $sift_score) {
+        $sift_score = 1 - $sift_score;
+        $sift_score = 0.999 if $sift_score == 1;
+        $sift_score = 0.0001 if $sift_score == 0;
+    }
+
+    if (defined $pph_score && defined $sift_score) {
+        
+        my $pph_weight  = log(1/(1-$pph_score));
+        my $sift_weight = log(1/(1-$sift_score));
+       
+        # we take -qnorm, because the R script uses qnorm(..., lower.tail = FALSE)
+
+        my $pph_z   = -qnorm($pph_score);
+        my $sift_z  = -qnorm($sift_score);
+        
+        my $numerator   = ($pph_weight * $pph_z) + ($sift_weight * $sift_z);
+        my $denominator = sqrt( ($pph_weight ** 2) + ($sift_weight ** 2) );
+
+        # likewise we take 1 - pnorm
+
+        $carol_score = 1 - pnorm($numerator / $denominator);
+    }
+    elsif (defined $pph_score) {
+        $carol_score = $pph_score;
+    }
+    else {
+        $carol_score = $sift_score;
+    }
+
+    if (defined $carol_score) {
+        my $carol_pred = $carol_score < $CAROL_CUTOFF ? 'Neutral' : 'Deleterious';
+        return ($carol_pred, $carol_score);
+    }
+    else {
+        return undef;
+    }
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/Condel.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,261 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ Condel
+
+=head1 SYNOPSIS
+
+ mv Condel.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin Condel,/path/to/config/Condel/config,b
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that calculates
+ the Consensus Deleteriousness (Condel) score (1) for a missense mutation 
+ based on the pre-calculated SIFT (2) and PolyPhen-2 (3) scores from the Ensembl 
+ API (4). It adds one new entry class to the VEP's Extra column, Condel which is
+ the calculated Condel score. This version of Condel was developed by the Biomedical Genomics Group 
+ of the Universitat Pompeu Fabra, at the Barcelona Biomedical Research Park and available at
+ (http://bg.upf.edu/condel) until April 2014. The code in this plugin is based on a script provided by this 
+ group and slightly reformatted to fit into the Ensembl API.
+
+ The plugin takes 3 command line arguments, the first is the path to a Condel 
+ configuration directory which contains cutoffs and the distribution files etc., 
+ the second is either "s", "p", or "b" to output the Condel score, prediction or 
+ both (the default is both), and the third argument is either 1 or 2 to use the 
+ original version of Condel (1), or the newer version (2) - 2 is the default and 
+ is recommended to avoid false positive predictions from Condel in some 
+ circumstances.
+
+ An example Condel configuration file and a set of distribution files can be found 
+ in the config/Condel directory in this repository. You should edit the 
+ config/Condel/config/condel_SP.conf file and set the 'condel.dir' parameter to
+ the full path to the location of the config/Condel directory on your system.
+
+ References:
+
+ (1) Gonzalez-Perez A, Lopez-Bigas N. 
+     Improving the assessment of the outcome of non-synonymous SNVs with a Consensus deleteriousness score (Condel)
+     Am J Hum Genet 88(4):440-449 (2011)
+     doi:10.1016/j.ajhg.2011.03.004
+
+ (2) Kumar P, Henikoff S, Ng PC.
+     Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm
+     Nature Protocols 4(8):1073-1081 (2009)
+     doi:10.1038/nprot.2009.86
+ 
+ (3) Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P, Kondrashov AS, Sunyaev SR. 
+     A method and server for predicting damaging missense mutations
+     Nature Methods 7(4):248-249 (2010)
+     doi:10.1038/nmeth0410-248
+ 
+ (4) Flicek P, et al.
+     Ensembl 2012
+     Nucleic Acids Research (2011)
+     doi: 10.1093/nar/gkr991
+
+=cut
+
+package Condel;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub version {
+    return '2.4';
+}
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub get_header_info {
+    return {
+        Condel => "Consensus deleteriousness score for an amino acid substitution based on SIFT and PolyPhen-2",
+    };
+}
+
+sub new {
+    my $class = shift;
+    
+    my $self = $class->SUPER::new(@_);
+
+    # parse the config file and distribution files 
+
+    my $config_dir = $self->params->[0];
+    $self->{output} = $self->params->[1] || 'b';
+    $self->{version} = $self->params->[2] || 2;
+
+    # find config dir
+    unless($config_dir && -d $config_dir) {
+        $config_dir = $INC{'Condel.pm'};
+        $config_dir =~ s/Condel\.pm/config\/Condel\/config/;
+        die "ERROR: Unable to find Condel config path\n" unless -d $config_dir;
+    }
+    
+    my $config_file = "$config_dir/condel_SP.conf";
+
+    open(CONF, "<$config_file") || die "Could not open $config_file";
+
+    my @conf = <CONF>;
+    
+    my $safe_conf = 0;
+    
+    for (my $i = 0; $i < @conf; $i++){
+        if ($conf[$i] =~ /condel\.dir=\'(\S+)\'/){
+            $self->{config}->{'condel.dir'} = $1;
+
+            # user has not edited config, attempt to get correct dir
+            if($self->{config}->{'condel.dir'} eq 'path/to/config/Condel/') {
+                my $dir = $INC{'Condel.pm'};
+                $dir =~ s/Condel\.pm/config\/Condel/;
+                $self->{config}->{'condel.dir'} = $dir;
+            }
+            $safe_conf++ if -d $self->{config}->{'condel.dir'};
+        }
+        elsif ($conf[$i] =~ /(cutoff\.HumVar\.\w+)=\'(\S+)\'/){
+            $self->{config}->{$1} = $2;
+            $safe_conf++;
+        }
+        elsif ($conf[$i] =~ /(max\.HumVar\.\w+)=\'(\S+)\'/){
+            $self->{config}->{$1} = $2;
+            $safe_conf++;
+        }
+    }
+
+    if ($safe_conf < 3){
+        die "Malformed config file!!!\n\n";
+    }
+
+    open(SIFT, $self->{config}->{'condel.dir'}."/methdist/sift.data");
+    my @sift = <SIFT>;
+    close SIFT;
+
+    for (my $i = 0; $i < @sift; $i++){
+        if ($sift[$i] =~ /(\S+)\s+(\S+)\s+(\S+)/){
+            $self->{sift}->{tp}->{$1} = $2;
+            $self->{sift}->{tn}->{$1} = $3;
+        }
+    }
+
+    open(POLYPHEN, $self->{config}->{'condel.dir'}."/methdist/polyphen.data");
+    my @polyphen = <POLYPHEN>;
+    close POLYPHEN;
+
+    for (my $i = 0; $i < @polyphen; $i++){
+        if ($polyphen[$i] =~ /(\S+)\s+(\S+)\s+(\S+)/){
+            $self->{polyphen}->{tp}->{$1} = $2;
+            $self->{polyphen}->{tn}->{$1} = $3;
+        }
+    }
+
+    return $self;
+}
+
+sub run {
+    my ($self, $tva) = @_;
+    
+    my $pph_score   = $tva->polyphen_score;
+    my $pph_pred    = $tva->polyphen_prediction;
+    my $sift_score  = $tva->sift_score;
+
+    my $results = {};
+
+    if (defined $pph_score && defined $sift_score && $pph_pred ne 'unknown') {
+
+        my ($condel_pred, $condel_score) = $self->compute_condel($sift_score, $pph_score);
+
+        $condel_score = sprintf "%.3f", $condel_score;
+            
+        my $output = "$condel_pred($condel_score)";
+        
+        $output = $condel_pred if ($self->{output} =~ /^p/);
+        $output = $condel_score if ($self->{output} =~ /^s/);
+
+        $results = {
+            Condel => $output,
+        };
+    }
+
+    return $results;
+}
+
+sub compute_condel {
+
+    my ($self, $sift_score, $polyphen_score) = @_;
+
+    my $USE_V2 = $self->{version} == 2;
+
+    my $class;
+    
+    my $base = 0;
+    my $int_score = 0;
+
+    $sift_score     = sprintf("%.3f", $sift_score);
+    $polyphen_score = sprintf("%.3f", $polyphen_score);
+    
+    if ($sift_score <= $self->{config}->{'cutoff.HumVar.sift'}){
+        $int_score += sprintf("%.3f", (1 - $sift_score/$self->{config}->{'max.HumVar.sift'})*(1-$self->{sift}->{tn}->{$sift_score}));
+        $base += $USE_V2 ? 1 : 1-$self->{sift}->{tn}->{$sift_score};
+    }
+    else {
+        $int_score += sprintf("%.3f", (1 - $sift_score/$self->{config}->{'max.HumVar.sift'})*(1-$self->{sift}->{tp}->{$sift_score}));
+        $base += $USE_V2 ? 1 : 1-$self->{sift}->{tp}->{$sift_score};
+    }
+    
+    if ($polyphen_score >= $self->{config}->{'cutoff.HumVar.polyphen'}){
+        $int_score += sprintf("%.3f", $polyphen_score/$self->{config}->{'max.HumVar.polyphen'}*(1-$self->{polyphen}->{tn}->{$polyphen_score}));
+        $base += $USE_V2 ? 1 : 1-$self->{polyphen}->{tn}->{$polyphen_score};
+    }
+    else {
+        $int_score += sprintf("%.3f", $polyphen_score/$self->{config}->{'max.HumVar.polyphen'}*(1-$self->{polyphen}->{tp}->{$polyphen_score}));
+        $base += $USE_V2 ? 1 : 1-$self->{polyphen}->{tp}->{$polyphen_score};
+    }
+
+    if ($base == 0){
+        $int_score = -1;
+        $class = 'not_computable_was';
+    }
+    else {
+        $int_score = sprintf("%.3f", $int_score/$base);
+    }
+
+    if ($int_score >= 0.469){
+        $class = 'deleterious';
+    }
+    elsif ($int_score >= 0 && $int_score < 0.469) {
+        $class = 'neutral';
+    }
+
+    # if the user wants an array, return the class and score, otherwise just return the class
+        
+    return ($class, $int_score);
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/Conservation.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,222 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ Conservation
+
+=head1 SYNOPSIS
+
+ mv Conservation.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin Conservation,GERP_CONSERVATION_SCORE,mammals
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+ retrieves a conservation score from the Ensembl Compara databases
+ for variant positions. You can specify the method link type and
+ species sets as command line options, the default is to fetch GERP
+ scores from the EPO 35 way mammalian alignment (please refer to the
+ Compara documentation for more details of available analyses). 
+
+ If a variant affects multiple nucleotides the average score for the
+ position will be returned, and for insertions the average score of
+ the 2 flanking bases will be returned.
+
+ The plugin requires the ensembl-compara API module to be installed;
+ see http://www.ensembl.org/info/docs/api/index.html
+
+=cut
+
+package Conservation;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Registry;
+use Bio::EnsEMBL::Slice;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub version {
+    return '2.3';
+}
+
+sub feature_types {
+    return ['Feature','Intergenic'];
+}
+
+sub get_header_info {
+
+    my $self = shift;
+    
+    return {
+        Conservation => "The conservation score for this site (method_link_type=\"".
+            $self->{method_link_type}."\", species_set=\"".$self->{species_set}."\")",
+    };
+}
+
+sub new {
+    my $class = shift;
+
+    my $self = $class->SUPER::new(@_);
+
+    my $params = $self->params;
+
+    # REST API passes 1 as first param
+    shift @$params if $params->[0] && $params->[0] eq '1';
+
+    $self->{method_link_type} = $params->[0] || 'GERP_CONSERVATION_SCORE';
+    $self->{species_set}  = $params->[1] || 'mammals';
+
+    my $config = $self->{config};
+    my $reg = 'Bio::EnsEMBL::Registry';
+
+    # reconnect to DB without species param
+    if($config->{host}) {
+        $reg->load_registry_from_db(
+            -host       => $config->{host},
+            -user       => $config->{user},
+            -pass       => $config->{password},
+            -port       => $config->{port},
+            -db_version => $config->{db_version},
+            -no_cache   => $config->{no_slice_cache},
+        );
+    }
+
+    my $mlss_adap = $config->{mlssa} ||= $reg->get_adaptor('Multi', 'compara', 'MethodLinkSpeciesSet')
+        or die "Failed to connect to compara database\n";
+
+    $self->{mlss} = $mlss_adap->fetch_by_method_link_type_species_set_name($self->{method_link_type}, $self->{species_set})
+        or die "Failed to fetch MLSS for ".$self->{method_link_type}." and ".$self->{species_set}."\n";
+
+    $self->{cs_adap} = $config->{cosa} ||= $reg->get_adaptor('Multi', 'compara', 'ConservationScore')
+        or die "Failed to fetch conservation adaptor\n";
+
+    return $self;
+}
+
+sub run {
+    my ($self, $bvfoa) = @_;
+
+    my $bvf = $bvfoa->base_variation_feature;
+
+    # we cache the score on the BaseVariationFeature so we don't have to
+    # fetch it multiple times if this variant overlaps multiple Features
+
+    unless (exists $bvf->{_conservation_score}) {
+
+        my $slice;
+
+        my $true_snp = 0;
+
+        if ($bvf->{end} >= $bvf->{start}) {
+
+            if ($bvf->{start} == $bvf->{end}) {
+
+                # work around a bug in the compara API that means you can't fetch 
+                # conservation scores for 1bp slices by creating a 2bp slice for
+                # SNPs and then ignoring the score returned for the second position
+
+                my $s = $bvf->slice;
+
+                $slice = Bio::EnsEMBL::Slice->new(
+                    -seq_region_name   => $s->seq_region_name,
+                    -seq_region_length => $s->seq_region_length,
+                    -coord_system      => $s->coord_system,
+                    -start             => $bvf->{start},
+                    -end               => $bvf->{end} + 1,
+                    -strand            => $bvf->{strand},
+                    -adaptor           => $s->adaptor
+                );
+                
+                $true_snp = 1;
+            }
+            else {
+
+                # otherwise, just get a slice that covers our variant feature
+
+                $slice = $bvf->feature_Slice;
+            }
+        }
+        else {
+
+            # this is an insertion, we return the average score of the flanking 
+            # bases, so we create a 2bp slice around the insertion site
+
+            my $s = $bvf->slice;
+
+            $slice = Bio::EnsEMBL::Slice->new(
+                -seq_region_name   => $s->seq_region_name,
+                -seq_region_length => $s->seq_region_length,
+                -coord_system      => $s->coord_system,
+                -start             => $bvf->{end},
+                -end               => $bvf->{start},
+                -strand            => $bvf->{strand},
+                -adaptor           => $s->adaptor
+            );
+        }
+
+        my $scores = $self->{cs_adap}->fetch_all_by_MethodLinkSpeciesSet_Slice(
+            $self->{mlss},                      # our MLSS for the conservation metric and the set of species
+            $slice,                             # our slice
+            ($slice->end - $slice->start + 1),  # the number of scores we want back (one for each base)
+        );
+
+        if (@$scores > 0) {
+
+            # we use the simple average of the diff_scores as the overall score
+            
+            pop @$scores if $true_snp; # get rid of our spurious second score for SNPs
+            
+            if (@$scores > 0) {
+
+                my $tot_score = 0;
+    
+                $tot_score += $_->diff_score for @$scores;
+    
+                $tot_score /= @$scores;
+                
+                $bvf->{_conservation_score} = sprintf "%.3f", $tot_score;
+            }
+            else {
+                $bvf->{_conservation_score} = undef;
+            }
+        }
+        else {
+            $bvf->{_conservation_score} = undef;
+        }
+    }
+
+    if (defined $bvf->{_conservation_score}) {
+        return {
+            Conservation => $bvf->{_conservation_score}
+        };
+    }
+    else {
+        return {};
+    }
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/DAS.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,127 @@
+=head1 LICENSE
+                                                                                                                     
+ Copyright (c) 1999-2015 The European Bioinformatics Institute and
+ Genome Research Limited.  All rights reserved.                                                                      
+                                                                                                                     
+ This software is distributed under a modified Apache license.                                                       
+ For license details, please see
+
+   http://www.ensembl.org/info/about/code_licence.html                                                               
+                                                                                                                     
+=head1 CONTACT                                                                                                       
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ DAS
+
+=head1 SYNOPSIS
+
+ mv DAS.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin DAS,<DAS_server>,<DAS_source>,<proxy>
+
+=head1 DESCRIPTION
+
+ A simple VEP plugin that checks for DAS features overlapping variants. Currently assumes that
+ the assemblies match, and doesn't do any smart fetching of chunks of features (i.e. the plugin
+ will query the DAS server once for every variant in the input file).
+
+ You can run multiple instances of this plugin at the same time so you can query multiple DAS
+ servers and sources. If you are querying multiple sources from the same server it is 
+ convenient to store the server name in an environment variable to avoid specifying it
+ multiple times, e.g.:
+
+ export DAS="http://somewhere/das"
+ ./vep -i variations.vcf --plugin DAS,$DAS,source1 --plugin DAS,$DAS,source2
+
+ Requires the Bio::Das::Lite module from CPAN.
+
+=cut
+
+package DAS;
+
+use strict;
+use warnings;
+
+use Bio::Das::Lite;
+use Data::Dumper;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub get_header_info {
+    my $self = shift;
+    return {
+        $self->header => $self->{source}." features from DAS server ".$self->{server},
+    };
+}
+
+sub feature_types {
+    return ['Transcript','RegulatoryFeature','MotifFeature','Intergenic'];
+}
+
+sub new {
+    my $class = shift;
+    
+    my $self = $class->SUPER::new(@_);
+
+    my ($server, $source, $proxy) = @{ $self->params };
+
+    # strip off any trailing slash from the server URL
+    $server =~ s/\/$//;
+
+    $self->{das} = Bio::Das::Lite->new({
+        timeout     => 10000,
+        dsn         => "$server/$source",
+        http_proxy  => $proxy,
+    }) || die "Failed to connect to DAS source: $server/$source";
+
+    $self->{source} = $source;
+    $self->{server} = $server;
+
+    return $self;
+}
+
+sub header {
+    my $self = shift;
+    return 'DAS_'.$self->{source};
+}
+
+sub run {
+    my ($self, $vfoa) = @_;
+
+    my $vf = $vfoa->variation_feature;
+
+    my $segment = $vf->seq_region_name .':'.$vf->seq_region_start.','.$vf->seq_region_end;
+
+    # cache the results on the variation feature, making sure the cache key is unique given
+    # that there may be multiple DAS plugins running
+
+    my $cache_key = '_vep_das_cache_'.$self->{server}.$self->{source};
+
+    unless (exists $vf->{$cache_key}->{$segment}) {
+
+        $vf->{$cache_key}->{$segment} = [];
+
+        if (my $response = $self->{das}->features($segment)) {
+            for my $url (keys %$response) {
+                if (ref $response->{$url} eq 'ARRAY') { 
+                    for my $feat (@{ $response->{$url} }) {
+                        push @{ $vf->{$cache_key}->{$segment} }, $feat->{feature_label}.'('.$feat->{type}.')';
+                    }
+                }
+            }
+        }
+    }
+    
+    my $res = join ',', @{ $vf->{$cache_key}->{$segment} };
+
+    return $res ? {$self->header => $res} : {};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/Downstream.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,137 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ Downstream
+
+=head1 SYNOPSIS
+
+ mv Downstream.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin Downstream
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+ predicts the downstream effects of a frameshift variant on the protein
+ sequence of a transcript. It provides the predicted downstream protein
+ sequence (including any amino acids overlapped by the variant itself),
+ and the change in length relative to the reference protein.
+ 
+ Note that changes in splicing are not predicted - only the existing
+ translateable (i.e. spliced) sequence is used as a source of
+ translation. Any variants with a splice site consequence type are
+ ignored.
+
+=cut
+
+package Downstream;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+use POSIX qw(ceil);
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub version {
+    return '2.3';
+}
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub variant_feature_types {
+    return ['VariationFeature'];
+}
+
+sub get_header_info {
+    return {
+        DownstreamProtein   => "Predicted downstream translation for frameshift mutations",
+        ProteinLengthChange => "Predicted change in protein product length",
+    };
+}
+
+sub run {
+    my ($self, $tva) = @_;
+    
+    my @ocs = @{$tva->get_all_OverlapConsequences};
+    
+    if(grep {$_->SO_term eq 'frameshift_variant'} @ocs) {
+        
+        # can't do it for splice sites
+        return {} if grep {$_->SO_term =~ /splice/} @ocs;
+        
+        my $tv = $tva->transcript_variation;
+        my $tr = $tv->transcript;
+        my $cds_seq = defined($tr->{_variation_effect_feature_cache}) ? $tr->{_variation_effect_feature_cache}->{translateable_seq} : $tr->translateable_seq;
+        
+        # get the sequence to translate
+        my ($low_pos, $high_pos) = sort {$a <=> $b} ($tv->cds_start, $tv->cds_end);
+        my $is_insertion         = $tv->cds_start > $tv->cds_end ? 1 : 0;
+        my $last_complete_codon  = (ceil($low_pos / 3) - 1) * 3;
+        my $before_var_seq       = substr $cds_seq, $last_complete_codon, $low_pos - $last_complete_codon - ($is_insertion ? 0 : 1);
+        my $after_var_seq        = substr $cds_seq, $high_pos - ($is_insertion ? 1 : 0);
+        my $to_translate         = $before_var_seq.$tva->feature_seq.$after_var_seq;
+        my $three_prime_utr_seq  = $tr->three_prime_utr->seq() if ($tr->three_prime_utr);
+        $to_translate            = $to_translate.$three_prime_utr_seq if ($three_prime_utr_seq);
+        $to_translate            =~ s/\-//g;
+        
+        # create a bioperl object
+        my $codon_seq = Bio::Seq->new(
+          -seq      => $to_translate,
+          -moltype  => 'dna',
+          -alphabet => 'dna'
+        );
+        
+        # get codon table
+        my $codon_table;
+        if(defined($tr->{_variation_effect_feature_cache})) {
+            $codon_table = $tr->{_variation_effect_feature_cache}->{codon_table} || 1;
+        }
+        else {
+            my ($attrib) = @{$tr->slice->get_all_Attributes('codon_table')};
+            $codon_table = $attrib ? $attrib->value || 1 : 1;
+        }
+        
+        # translate
+        my $new_pep = $codon_seq->translate(undef, undef, undef, $codon_table)->seq();
+        $new_pep =~ s/\*.*//;
+        
+        # compare lengths
+        my $translation = defined($tr->{_variation_effect_feature_cache}) && defined($tr->{_variation_effect_feature_cache}->{peptide}) ? $tr->{_variation_effect_feature_cache}->{peptide} : $tr->translation->seq;
+        my $new_length = ($tv->translation_start < $tv->translation_end ? $tv->translation_start : $tv->translation_end) + length($new_pep);
+        
+        return {
+            DownstreamProtein   => $new_pep,
+            ProteinLengthChange => $new_length - length($translation),
+        };
+    }
+
+    return {};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/Draw.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,387 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ Draw
+
+=head1 SYNOPSIS
+
+ mv Draw.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin Draw
+
+=head1 DESCRIPTION
+
+ A VEP plugin that draws pictures of the transcript model showing the
+ variant location. Can take five optional paramters:
+ 
+ 1) File name stem for images
+ 2) Image width in pixels (default: 1000px)
+ 3) Image height in pixels (default: 100px)
+ 4) Transcript ID - only draw images for this transcript
+ 5) Variant ID - only draw images for this variant
+ 
+ e.g.
+ 
+ ./vep -i variations.vcf --plugin Draw,myimg,2000,100
+ 
+ Images are written to [file_stem]_[transcript_id]_[variant_id].png
+ 
+ Requires GD library installed to run.
+
+=cut
+
+package Draw;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+# GD libraries for image creating
+use GD;
+use GD::Polygon;
+
+use Bio::EnsEMBL::Variation::Utils::VariationEffect qw(MAX_DISTANCE_FROM_TRANSCRIPT);
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+
+sub new {
+    my $class = shift;
+
+    my $self = $class->SUPER::new(@_);
+    
+    # configure
+    my @params = @{$self->params};
+    
+    $self->{prefix}     = $params[0] || $self->{config}->{output_file};
+    $self->{width}      = $params[1] || 1000;
+    $self->{height}     = $params[2] || 100;
+    $self->{transcript} = $params[3] || undef;
+    $self->{variant}    = $params[4] || undef;
+
+    return $self;
+}
+
+sub version {
+    return '2.4';
+}
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub variant_feature_types {
+    return ['BaseVariationFeature'];
+}
+
+sub get_header_info {
+    return {};
+}
+
+sub run {
+    my ($self, $tva) = @_;
+    
+    my $main_tr = $tva->feature;
+    my $vf = $tva->base_variation_feature;
+    
+    return {} if defined($self->{transcript}) && $main_tr->stable_id ne $self->{transcript};
+    return {} if defined($self->{variant}) && $vf->variation_name ne $self->{variant};
+    
+    # if we're showing a gene fusion, get 
+    my $second_tr = $tva->{_fusion_transcripts}->[0] if grep {$_->SO_term =~ /gene_fusion/} @{$tva->get_all_OverlapConsequences};
+    
+    # set up scales etc
+    my $width    = $main_tr->feature_Slice->length + (2 * MAX_DISTANCE_FROM_TRANSCRIPT);
+    my $tr_start = $main_tr->start - MAX_DISTANCE_FROM_TRANSCRIPT;
+    my $tr_end   = $main_tr->end + MAX_DISTANCE_FROM_TRANSCRIPT;
+    
+    if(defined($second_tr)) {
+        $width    = (max(($main_tr->end, $second_tr->end)) - min(($main_tr->start, $second_tr->start))) + 1 + (2 * MAX_DISTANCE_FROM_TRANSCRIPT);
+        $tr_start = min(($main_tr->start, $second_tr->start)) - MAX_DISTANCE_FROM_TRANSCRIPT;
+        $tr_end   = max(($main_tr->end, $second_tr->end)) + MAX_DISTANCE_FROM_TRANSCRIPT;
+    }
+    
+    my $x_scale  = ($self->{width} - 20)  / $width;
+    my $y_scale  = ($self->{height} - 30) / 100;
+    my $x_off    = 10;
+    my $y_off    = 20;
+    
+    # create GD image object
+    my $img = GD::Image->new($self->{width}, $self->{height});
+    
+    # set up some colours
+    my %colours = (
+        white      => $img->colorAllocate(255,255,255),
+        black      => $img->colorAllocate(0,0,0),
+        grey       => $img->colorAllocate(200,200,200),
+        darkgrey   => $img->colorAllocate(150,150,150),
+        vlightgrey => $img->colorAllocate(235,235,235),
+        blue       => $img->colorAllocate(0,0,200),
+        lightblue  => $img->colorAllocate(200,200,255),
+        red        => $img->colorAllocate(200,0,0),
+        lightred   => $img->colorAllocate(255,200,200),
+        green      => $img->colorAllocate(0,200,0),
+        lightgreen => $img->colorAllocate(220,255,220),
+        yellow     => $img->colorAllocate(236,164,26),
+        purple     => $img->colorAllocate(195,50,212),  
+    );
+    
+    # scale bar
+    my $zero_string = '0' x (length(int(100 / $x_scale)) - 1);
+    my $bases_per_bar = '1'.$zero_string;
+    
+    my $start = int($tr_start / $bases_per_bar) * $bases_per_bar;
+    my $end = (int($tr_start / $bases_per_bar) + 1) * $bases_per_bar;
+    my $colour = 0;
+    
+    while($start < $tr_end) {
+        my $method = $colour ? 'rectangle' : 'filledRectangle';
+        
+        $img->$method(
+            $x_off + (($start - $tr_start) * $x_scale),
+            $self->{height} - 15,
+            $x_off + (($end - $tr_start) * $x_scale),
+            $self->{height} - 10,
+            $colours{grey},
+        );
+        
+        # tick and label
+        if($start =~ /(5|0)$zero_string$/) {
+            my $string = $start;
+            1 while $string =~ s/^(-?\d+)(\d\d\d)/$1,$2/;
+            
+            $img->string(
+                gdTinyFont,
+                $x_off + (($start - $tr_start) * $x_scale) + 2,
+                $self->{height} - 8,
+                $string,
+                $colours{black}
+            );
+            
+            $img->line(
+                $x_off + (($start - $tr_start) * $x_scale),
+                $self->{height} - 15,
+                $x_off + (($start - $tr_start) * $x_scale),
+                $self->{height},
+                $start =~ /5$zero_string$/ ? $colours{grey} : $colours{black}
+            );
+            
+            $img->dashedLine(
+                $x_off + (($start - $tr_start) * $x_scale),
+                0,
+                $x_off + (($start - $tr_start) * $x_scale),
+                $self->{height} - 15,
+                $start =~ /5$zero_string$/ ? $colours{vlightgrey} : $colours{grey}
+            )
+        }
+        
+        $colour = 1 - $colour;
+        $start += $bases_per_bar;
+        $end += $bases_per_bar;
+    }
+    
+    # render transcripts
+    foreach my $tr($main_tr, $second_tr) {
+        next unless defined($tr);
+        
+        # render introns
+        foreach my $intron(@{$tr->get_all_Introns}) {
+            $img->line(
+                $x_off + (($intron->start - $tr_start) * $x_scale),
+                $y_off + (20 * $y_scale),
+                $x_off + (((($intron->start + $intron->end) / 2) - $tr_start) * $x_scale),
+                $y_off + (10 * $y_scale),
+                $colours{lightblue}
+            );
+            
+            $img->line(
+                $x_off + (((($intron->start + $intron->end) / 2) - $tr_start) * $x_scale),
+                $y_off + (10 * $y_scale),
+                $x_off + (($intron->end - $tr_start) * $x_scale),
+                $y_off + (20 * $y_scale),
+                $colours{lightblue}
+            );
+        }
+        
+        # render exons
+        foreach my $exon(@{$tr->get_all_Exons}) {
+            
+            # non-coding part
+            $img->rectangle(
+                $x_off + (($exon->start - $tr_start) * $x_scale),
+                $y_off + (10 * $y_scale),
+                $x_off + (($exon->end - $tr_start) * $x_scale),
+                $y_off + (30 * $y_scale),
+                $colours{lightblue}
+            );
+            
+            # coding part
+            $img->filledRectangle(
+                $x_off + (($exon->coding_region_start($tr) - $tr_start) * $x_scale),
+                $y_off + (0 * $y_scale),
+                $x_off + (($exon->coding_region_end($tr) - $tr_start) * $x_scale),
+                $y_off + (40 * $y_scale),
+                $colours{blue}
+            ) if defined $exon->coding_region_start($tr) && defined $exon->coding_region_end($tr);
+        }
+        
+        # add transcript direction indicator
+        if($tr->strand == 1) {
+            
+            # vertical line
+            $img->line(
+                $x_off + (($tr->start - $tr_start) * $x_scale),
+                $y_off + (-5 * $y_scale),
+                $x_off + (($tr->start - $tr_start) * $x_scale),
+                $y_off + (20 * $y_scale),
+                $colours{lightblue},
+            );
+            
+            # horizontal line
+            $img->line(
+                $x_off + (($tr->start - $tr_start) * $x_scale),
+                $y_off + (-5 * $y_scale),
+                $x_off + (($tr->start - $tr_start) * $x_scale) + 20,
+                $y_off + (-5 * $y_scale),
+                $colours{lightblue},
+            );
+            
+            # top arrow part
+            $img->line(
+                $x_off + (($tr->start - $tr_start) * $x_scale) + 17,
+                $y_off + (-8 * $y_scale),
+                $x_off + (($tr->start - $tr_start) * $x_scale) + 20,
+                $y_off + (-5 * $y_scale),
+                $colours{lightblue},
+            );
+            
+            # bottom arrow part
+            $img->line(
+                $x_off + (($tr->start - $tr_start) * $x_scale) + 17,
+                $y_off + (-1 * $y_scale),
+                $x_off + (($tr->start - $tr_start) * $x_scale) + 20,
+                $y_off + (-5 * $y_scale),
+                $colours{lightblue},
+            );
+            
+            # label
+            $img->string(gdTinyFont, $x_off + (($tr->start - $tr_start) * $x_scale) + 25, $y_off + (-12 * $y_scale), $tr->stable_id, $colours{blue});
+        }
+        
+        else {        
+            
+            # vertical line
+            $img->line(
+                $x_off + (($tr->end - $tr_start) * $x_scale),
+                $y_off + (20 * $y_scale),
+                $x_off + (($tr->end - $tr_start) * $x_scale),
+                $y_off + (47 * $y_scale),
+                $colours{lightblue},
+            );
+            
+            # horizontal line
+            $img->line(
+                $x_off + (($tr->end - $tr_start) * $x_scale),
+                $y_off + (47 * $y_scale),
+                $x_off + (($tr->end - $tr_start) * $x_scale) - 20,
+                $y_off + (47 * $y_scale),
+                $colours{lightblue},
+            );
+            
+            # top arrow part
+            $img->line(
+                $x_off + (($tr->end - $tr_start) * $x_scale) - 17,
+                $y_off + (50 * $y_scale),
+                $x_off + (($tr->end - $tr_start) * $x_scale) - 20,
+                $y_off + (47 * $y_scale),
+                $colours{lightblue},
+            );
+            
+            # bottom arrow part
+            $img->line(
+                $x_off + (($tr->end - $tr_start) * $x_scale) - 17,
+                $y_off + (43 * $y_scale),
+                $x_off + (($tr->end - $tr_start) * $x_scale) - 20,
+                $y_off + (47 * $y_scale),
+                $colours{lightblue},
+            );
+            
+            # label
+            $img->string(gdTinyFont, $x_off + (($tr->end - $tr_start) * $x_scale) - 100, $y_off + (43 * $y_scale), $tr->stable_id, $colours{blue});
+        }
+    }
+    
+    # render variant
+    my $var_colour = 'green';
+    
+    if($vf->class_SO_term =~ /deletion/) {
+        $var_colour = 'red';
+    }
+    
+    $img->filledRectangle(
+        $x_off + (($vf->start - $tr_start) * $x_scale),
+        $y_off + (60 * $y_scale),
+        $x_off + (($vf->end - $tr_start) * $x_scale),
+        $y_off + (70 * $y_scale),
+        $colours{$var_colour},
+    );
+    
+    # variant label
+    $img->string(
+        gdTinyFont,
+        $x_off + (($vf->start - $tr_start) * $x_scale),
+        $y_off + (75 * $y_scale),
+        $vf->variation_name,
+        $colours{$var_colour}
+    );
+    
+    my $vname = $vf->variation_name;
+    $vname =~ s/\//\_/g;
+    my $file = $self->{prefix}."_".$main_tr->stable_id."_".(defined($second_tr) ? $second_tr->stable_id."_" : "").$vname."\.png";
+    
+    # check we're allowed to write to it
+    if(!defined($self->{config}->{force_overwrite}) && -e $file) {
+        die "ERROR: Image file $file already exists - choose a different file name stem or use --force_overwrite\n";
+        return;
+    }
+    
+    open IM, ">$file" or die "ERROR: Could not write to file $file\n";
+    binmode IM;
+    print IM $img->png;
+    close IM;
+    
+    return {};
+}
+
+sub max {
+    return (sort {$a <=> $b} @_)[-1];
+}
+
+sub min {
+    return (sort {$a <=> $b} @_)[0];
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/ExAC.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,293 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ ExAC
+
+=head1 SYNOPSIS
+
+ mv ExAC.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin ExAC,/path/to/ExAC/ExAC.r0.3.sites.vep.vcf.gz
+ ./vep -i variations.vcf --plugin ExAC,/path/to/ExAC/ExAC.r0.3.sites.vep.vcf.gz,AC
+ ./vep -i variations.vcf --plugin ExAC,/path/to/ExAC/ExAC.r0.3.sites.vep.vcf.gz,,AN
+ ./vep -i variations.vcf --plugin ExAC,/path/to/ExAC/ExAC.r0.3.sites.vep.vcf.gz,AC,AN
+
+
+
+=head1 DESCRIPTION
+
+ A VEP plugin that retrieves ExAC allele frequencies.
+ 
+ Visit ftp://ftp.broadinstitute.org/pub/ExAC_release/current to download the latest ExAC VCF.
+ 
+ Note that the currently available version of the ExAC data file (0.3) is only available
+ on the GRCh37 assembly; therefore it can only be used with this plugin when using the
+ VEP on GRCh37. See http://www.ensembl.org/info/docs/tools/vep/script/vep_other.html#assembly
+ 
+ The tabix utility must be installed in your path to use this plugin.
+
+ The plugin takes 3 command line arguments. Second and third arguments are not mandatory. If AC specified as second
+ argument Allele counts per population will be included in output. If AN specified as third argument Allele specific
+ chromosome counts will be included in output.
+
+
+=cut
+
+package ExAC;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+use Bio::EnsEMBL::Variation::Utils::Sequence qw(get_matched_variant_alleles);
+
+use Bio::EnsEMBL::Variation::Utils::VEP qw(parse_line get_slice);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+  
+  # test tabix
+  die "ERROR: tabix does not seem to be in your path\n" unless `which tabix 2>&1` =~ /tabix$/;
+  
+  # get ExAC file
+  my $file = $self->params->[0];
+
+  # get AC,AN options
+  if (exists($self->params->[1]) && $self->params->[1] eq 'AC'){
+    $self->{display_ac} = 1;
+  }
+  else {
+    $self->{display_ac} = 0;
+  }
+
+  if (exists($self->params->[2]) && $self->params->[2] eq 'AN'){
+    $self->{display_an} = 1;
+  }
+  else {
+    $self->{display_an} = 0;
+  }
+
+  # remote files?
+  if($file =~ /tp\:\/\//) {
+    my $remote_test = `tabix -f $file 1:1-1 2>&1`;
+    print STDERR "$remote_test\n";
+    # if($remote_test && $remote_test !~ /get_local_version/) {
+    #   die "$remote_test\nERROR: Could not find file or index file for remote annotation file $file\n";
+    # }
+  }
+
+  # check files exist
+  else {
+    die "ERROR: ExAC file $file not found; you can download it from ftp://ftp.broadinstitute.org/pub/ExAC_release/current\n" unless -e $file;
+    die "ERROR: Tabix index file $file\.tbi not found - perhaps you need to create it first?\n" unless -e $file.'.tbi';
+  }
+  
+  $self->{file} = $file;
+  
+  return $self;
+}
+
+sub feature_types {
+  return ['Feature','Intergenic'];
+}
+
+sub get_header_info {
+  my $self = shift;
+  
+  if(!exists($self->{header_info})) {
+    open IN, "tabix -f -h ".$self->{file}." 1:1-1 |";
+    
+    my %headers = ();
+    my @lines = <IN>;
+    
+    while(my $line = shift @lines) {
+      if($line =~ /ID\=AC(\_[A-Zdj]+)?\,.*\"(.+)\"/) {
+        my ($pop, $desc) = ($1, $2);
+        
+        $desc =~ s/Counts?/frequency/i;
+        $pop ||= '';
+        
+        my $field_name = 'ExAC_AF'.$pop;
+        $headers{$field_name} = 'ExAC '.$desc;
+
+        if ($self->{display_ac}){
+          $field_name = 'ExAC_AC'.$pop;
+          $headers{$field_name} = 'ExAC'.$pop.' Allele count';
+        }
+        if ($self->{display_an}){
+          $field_name = 'ExAC_AN'.$pop;
+          $headers{$field_name} = 'ExAC'.$pop.' Allele number';
+        }
+
+        # store this header on self
+        push @{$self->{headers}}, 'AC'.$pop;
+      }
+    }
+    
+    close IN;
+    
+    die "ERROR: No valid headers found in ExAC VCF file\n" unless scalar keys %headers;
+    
+    $self->{header_info} = \%headers;
+  }
+  
+  return $self->{header_info};
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  # make sure headers have been loaded
+  $self->get_header_info();
+
+  my $vf = $tva->variation_feature;
+  my $name = $vf->variation_name;
+  
+  # get allele, reverse comp if needed
+  my $allele;
+  
+  $allele = $tva->variation_feature_seq;
+  reverse_comp(\$allele) if $vf->{strand} < 0;
+  
+  # adjust coords to account for VCF-like storage of indels
+  my ($s, $e) = ($vf->{start} - 1, $vf->{end} + 1);
+ 
+  my $vf_chr = $vf->{chr};
+  $vf_chr =~ s/chr//;
+  my $pos_string = sprintf("%s:%i-%i", $vf_chr, $s, $e);
+
+  
+  # clear cache if it looks like the coords are the same
+  # but allele type is different
+  delete $self->{cache} if
+    defined($self->{cache}->{$pos_string}) &&
+    scalar keys %{$self->{cache}->{$pos_string}} &&
+    !defined($self->{cache}->{$pos_string}->{$allele});
+  
+  my $data = {};
+  
+  # cached?
+  if(defined($self->{cache}) && defined($self->{cache}->{$pos_string})) {
+    $data = $self->{cache}->{$pos_string};
+  }
+  
+  # read from file
+  else {
+    open TABIX, sprintf("tabix -f %s %s |", $self->{file}, $pos_string);
+    
+    while(<TABIX>) {
+      chomp;
+      s/\r$//g;
+      # parse VCF line into a VariationFeature object
+      my ($vcf_vf) = @{parse_line({format => 'vcf', minimal => 1}, $_)};
+      
+      # check parsed OK
+      next unless $vcf_vf && $vcf_vf->isa('Bio::EnsEMBL::Variation::VariationFeature');
+
+      my @vcf_alleles = split /\//, $vcf_vf->allele_string;
+      my $ref_allele  = shift @vcf_alleles;
+      my $vcf_vf_start = $vcf_vf->{start};
+      my $vcf_vf_end = $vcf_vf->{end};
+
+      my @vf_alleles = split /\//, $vf->allele_string;
+      my $vf_ref_allele = shift @vf_alleles;
+
+      if ($vcf_vf_start != $vf->{start} || $vcf_vf_end != $vf->{end}) {
+        my $matched_alleles = get_matched_variant_alleles({ref => $vf_ref_allele, alts => [$allele], pos => $vf->{start}}, {ref => $ref_allele, alts => \@vcf_alleles,  pos => $vcf_vf_start});
+
+        next unless (@$matched_alleles);
+        # We only match one alt allele from the input VF against alleles from the VCF line. b_allele is the matched allele from the VCF alt alleles
+        $allele = $matched_alleles->[0]->{b_allele};
+      }
+      # iterate over required headers
+      HEADER:
+      foreach my $h(@{$self->{headers} || []}) {
+        my $total_ac = 0;
+        
+        if(/$h\=([0-9\,]+)/) {
+          
+          # grab AC
+          my @ac = split /\,/, $1;
+          next unless scalar @ac == scalar @vcf_alleles;
+          
+          # now sed header to get AN
+          my $anh = $h;
+          $anh =~ s/AC/AN/;
+          
+          my $afh = $h;
+          $afh =~ s/AC/AF/;
+
+          # get AC from header
+          my $ach = $h;
+
+          if(/$anh\=([0-9\,]+)/) {
+            
+            # grab AN
+            my @an = split /\,/, $1;
+            next unless @an;
+            my $an;
+
+            foreach my $a(@vcf_alleles) {
+              my $ac = shift @ac;
+              $an = shift @an if @an;
+
+              $total_ac += $ac;
+              if ($self->{display_ac}){
+                $data->{$a}->{'ExAC_'.$ach} = $ac;
+              }
+              if ($self->{display_an}){
+                $data->{$a}->{'ExAC_'.$anh} = $an;
+              }
+
+              $data->{$a}->{'ExAC_'.$afh} = sprintf("%.3g", $ac / $an) if $an;
+            }
+            
+            # use total to get ref allele freq
+            if ($self->{display_ac}){
+             $data->{$ref_allele}->{'ExAC_'.$ach} = $total_ac;
+            }
+            if ($self->{display_an}){
+              $data->{$ref_allele}->{'ExAC_'.$anh} = $an;
+            }
+            $data->{$ref_allele}->{'ExAC_'.$afh} = sprintf("%.3g", 1 - ($total_ac / $an)) if $an;
+          }
+        }
+      }
+    }
+    
+    close TABIX;
+  }
+  
+  # overwrite cache
+  $self->{cache} = {$pos_string => $data};
+  return defined($data->{$allele}) ? $data->{$allele} : {};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/ExACpLI.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,134 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Please email comments or questions to the public Ensembl
+ developers list at <http://lists.ensembl.org/mailman/listinfo/dev>.
+
+ Questions may also be sent to the Ensembl help desk at
+ <http://www.ensembl.org/Help/Contact>.
+
+=cut
+
+=head1 NAME
+
+ExACpLI - Add ExAC pLI to the VEP output 
+
+=head1 SYNOPSIS
+
+  mv ExACpLI.pm ~/.vep/Plugins
+  mv ExACpLI_values.txt ~/.vep/Plugins
+  ./vep -i variants.vcf --plugin ExACpLI
+
+=head1 DESCRIPTION
+
+
+  A VEP plugin that adds the probabililty of a gene being 
+  loss-of-function intolerant (pLI) to the VEP output.
+  
+  Lek et al. (2016) estimated pLI using the expectation-maximization 
+  (EM) algorithm and data from 60,706 individuals from 
+  ExAC (http://exac.broadinstitute.org/about). The closer pLI is to 1, 
+  the more likely the gene is loss-of-function (LoF) intolerant. 
+  
+  Note: the pLI was calculated using a representative transcript and
+  is reported by gene in the plugin.
+
+  The data for the plugin is provided by Kaitlin Samocha and Daniel MacArthur. 
+  See https://www.ncbi.nlm.nih.gov/pubmed/27535533 for a description 
+  of the dataset and analysis.
+
+  The ExACpLI_values.txt file is found alongside the plugin in the 
+  VEP_plugins GitHub repository. The file contains the fields gene and pLI 
+  extracted from the file at 
+    
+    ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3/functional_gene_constraint/
+      fordist_cleaned_exac_r03_march16_z_pli_rec_null_data.txt
+
+  To use another values file, add it as a parameter i.e.
+
+     ./vep -i variants.vcf --plugin ExACpLI,values_file.txt
+
+
+=cut
+
+package ExACpLI;
+
+use strict;
+use warnings;
+
+use DBI;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub new {
+  my $class = shift;
+
+  my $self = $class->SUPER::new(@_);
+  
+  my $file = $self->params->[0];
+
+  if(!$file) {
+    my $plugin_dir = $INC{'ExACpLI.pm'};
+    $plugin_dir =~ s/ExACpLI\.pm//i;
+    $file = $plugin_dir.'/ExACpLI_values.txt';
+  }
+  
+  die("ERROR: ExACpLI values file $file not found\n") unless $file && -e $file;
+  
+  open my $fh, "<",  $file;
+  my %scores;
+  
+  while(<$fh>) {
+    chomp;
+    my ($gene, $score) = split;
+    next if $score eq 'pLI';
+    $scores{lc($gene)} = sprintf("%.2f", $score);
+  }
+  
+  close $fh;
+  
+  die("ERROR: No scores read from $file\n") unless scalar keys %scores;
+  
+  $self->{scores} = \%scores;
+  
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  return {
+    ExACpLI => "ExACpLI value for gene"
+  };
+}
+
+sub run {
+  my $self = shift;
+  my $tva = shift;
+  
+  my $symbol = $tva->transcript->{_gene_symbol} || $tva->transcript->{_gene_hgnc};
+  return {} unless $symbol;
+  
+  return $self->{scores}->{lc($symbol)} ? { ExACpLI => $self->{scores}->{lc($symbol)}} : {};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/ExACpLI_values.txt	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,18226 @@
+gene	pLI
+AGRN	0.17335234048116
+NOC2L	1.33038194561114e-19
+B3GALT6	0.0481044658297901
+C1orf159	0.0908776364218918
+ISG15	0.00984781293610986
+KLHL17	2.51676266070248e-07
+PLEKHN1	2.01974835522321e-08
+SAMD11	1.35381157129201e-10
+OR4F5	0.176329298172162
+HES4	0.00014794288110518
+FAM132A	4.67625423888147e-05
+TNFRSF18	8.36589277636991e-07
+SDF4	0.0013098271899439
+TNFRSF4	0.00720932981621916
+TTLL10	1.94738806982348e-05
+UBE2J2	0.415938846926224
+ATAD3C	4.90849565539176e-05
+MRPL20	0.000171803357075406
+CPSF3L	5.7881402380741e-09
+AURKAIP1	0.00247538764889321
+SSU72	0.606848849205337
+GLTPD1	0.00138279022732508
+MXRA8	0.00471297228153819
+ACAP3	0.0394309302206711
+VWA1	0.0331997601703093
+ATAD3A	0.0401305978810457
+CCNL2	0.104548195351159
+DVL1	0.157164971605877
+SCNN1D	2.82187066585139e-15
+ATAD3B	1.92301228016303e-13
+PUSL1	6.58681964674524e-12
+C1orf86	0.785170903024389
+SKI	0.981402099833324
+CDK11B	0.72829443952872
+GNB1	0.995187833121982
+SLC35E2B	0.62100245921917
+CDK11A	5.23535259576534e-05
+NADK	0.00126768961404905
+PEX10	0.010463632475946
+CALML6	0.000127436926421093
+TMEM52	0.328693114330909
+MORN1	7.87931445985798e-07
+GABRD	0.923498878454823
+PRKCZ	0.266923656763182
+RER1	0.969239732851388
+MIB2	0.000158543294053226
+SLC35E2	0.374305907762633
+PRDM16	0.999843194473124
+TP73	0.975977778366269
+PLCH2	1.70518647543863e-08
+LRRC47	0.60383218752352
+DFFB	5.08618071063922e-05
+ACTRT2	0.0187224605335923
+ARHGEF16	9.36505312388017e-08
+TPRG1L	0.00284528475212618
+HES5	0.532717161921776
+C1orf174	0.0187425021060312
+MEGF6	4.42421031130217e-15
+FAM213B	0.000166699570192146
+CCDC27	1.60569656764963e-19
+WRAP73	0.0269219902261615
+CEP104	2.63081806867216e-08
+MMEL1	8.87673673427084e-13
+PANK4	0.945333401831958
+TNFRSF14	0.819999054408814
+KLHL21	0.00107735176759231
+NOL9	0.0044702400177699
+PLEKHG5	4.02821229083025e-05
+KCNAB2	0.839972632374732
+ICMT	0.95914542813838
+ESPN	0.00255384128821556
+AJAP1	0.977592766896285
+ZBTB48	0.680198376469515
+TNFRSF25	0.448738853101197
+TAS1R1	7.9136002871651e-09
+NPHP4	1.29374352876183e-17
+RPL22	0.348492156430072
+RNF207	5.19011202351337e-06
+HES3	0.268868568223653
+CHD5	0.999999995117076
+PHF13	0.931111283002542
+THAP3	0.00148422474585026
+ACOT7	0.381517901841213
+HES2	0.0670466550651167
+GPR153	0.000377954117161823
+VAMP3	0.0542630674689049
+SLC45A1	0.0451892558909179
+CA6	0.00802362076493995
+DNAJC11	0.999970790294974
+PIK3CD	0.999984294919708
+ENO1	0.0103734127326719
+SLC25A33	0.451158319130907
+ERRFI1	0.046551582399882
+SLC2A5	5.67732629021242e-05
+GPR157	2.63491769393547e-05
+UTS2	0.151041459001058
+SLC2A7	2.99498303352468e-17
+TMEM201	0.841903867149445
+TNFRSF9	0.253050500972917
+CAMTA1	0.999999955418418
+PARK7	0.903949397411231
+PER3	2.19067741322434e-10
+H6PD	0.000111404418020294
+SPSB1	0.709596082305861
+RERE	0.999995655258253
+PEX14	0.634568377657546
+CLSTN1	0.844214450133216
+APITD1-CORT	0.00852090111528864
+DFFA	0.00021837065189826
+TARDBP	0.980707836590808
+EXOSC10	1.65795367368417e-07
+LZIC	0.00197924734359642
+CORT	0.0098377909618654
+SRM	0.869848472217591
+PGD	0.968660462332331
+RBP7	0.408810205691644
+CTNNBIP1	0.0229867402741806
+C1orf200	0.0549230054401102
+CASZ1	0.999938476327784
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+C21orf58	3.74077237894162e-09
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+DGCR6	7.62101542352864e-07
+HIRA	0.999998171154956
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+C22orf29	5.80709519233968e-06
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+PRODH	4.75363149716848e-06
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+TXNRD2	1.06916304756314e-08
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+C22orf39	3.69004562054558e-07
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+ARVCF	8.21839210300339e-07
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+LZTR1	3.38323005538586e-52
+GGT2	0.804816509817502
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+RAB36	1.44185655300034e-05
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+FAM211B	1.90288538061698e-11
+SUSD2	1.32605754184724e-10
+GGT1	0.676974716705773
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+SLC2A11	5.45933694484048e-12
+UPB1	1.85086913944901e-07
+PIWIL3	9.86575487560156e-26
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+GGT5	1.39303239383364e-05
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+IKBKG	0.628614516375526
+LAGE3	0.227379900839686
+FAM50A	0.945400813260401
+PLXNA3	0.983112793293949
+SLC10A3	0.629239798913129
+ATP6AP1	0.827633657438673
+CMC4	0.164577983805174
+RAB39B	0.715196297042307
+VBP1	0.822547586801538
+TMLHE	0.00276292005354084
+MPP1	0.940116717603012
+SPRY3	0.00584474683683058
+GAB3	0.990602402777157
+BRCC3	0.0339670741642349
+FUNDC2	0.841264939337729
+CLIC2	0.493262623526124
+DKC1	0.9989001727892
+F8	0.999999811590639
+MTCP1	0.342313098947147
+IL9R	1.92052299627482e-06
+VAMP7	0.00463196348400117
+PCDH11Y	0.0363686431008104
+TGIF2LY	0.0768707616723098
+SRY	0.416019592282844
+RPS4Y1	0.502396329607095
+ZFY	0.255459999135225
+USP9Y	0.140701437950318
+AMELY	0.00205505416408899
+UTY	0.632058104202083
+KDM5D	0.0151340441544138
+TMSB4Y	0.334409877031708
+DDX3Y	0.773099529750687
+NLGN4Y	0.645547566883988
+EIF1AY	0.424064592561161
+RPS4Y2	0.00298794938170108

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/FATHMM.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,149 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ FATHMM
+
+=head1 SYNOPSIS
+
+ mv FATHMM.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin FATHMM,"python /path/to/fathmm/fathmm.py"
+
+=head1 DESCRIPTION
+
+ A VEP plugin that gets FATHMM scores and predictions for missense variants.
+ 
+ You will need the fathmm.py script and its dependencies (Python, Python
+ MySQLdb). You should create a "config.ini" file in the same directory as the
+ fathmm.py script with the database connection options. More information about
+ how to set up FATHMM can be found on the FATHMM website at
+ https://github.com/HAShihab/fathmm.
+ 
+ A typical installation could consist of:
+ 
+ > wget https://raw.github.com/HAShihab/fathmm/master/cgi-bin/fathmm.py
+ > wget ftp://supfam2.cs.bris.ac.uk/FATHMM/database/fathmm.v2.1.SQL
+ > mysql -h[host] -P[port] -u[user] -p[pass] -e"CREATE DATABASE fathmm"
+ > mysql -h[host] -P[port] -u[user] -p[pass] -Dfathmm < fathmm.v2.1.SQL
+ > echo "[DATABASE]\nHOST = [host]\nPORT = [port]\nUSER = [user]\nPASSWD = [pass]\nDB = fathmm\n" > config.ini
+
+=cut
+
+package FATHMM;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+  
+  # get command
+  my $command = $self->params->[0];
+  
+  die 'ERROR: No FATHMM command specified. Specify path to FATHMM with e.g. --plugin FATHMM,"python /path/to/fathmm/fathmm.py"\n' unless defined($command);
+  
+  die 'ERROR: Your FATHMM command does not look correct; it should looks something like "python /path/to/fathmm/fathmm.py"\n' unless $command =~ /python.+fathmm\.py/;
+  
+  $self->{command} = $command;
+  
+  die 'ERROR: Temporary directory '.$self->{config}->{tmpdir}.' not found - specify an existing directory with --tmpdir [dir]\n' unless -d $self->{config}->{tmpdir};
+  
+  return $self;
+}
+
+sub version {
+  return 71;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  return {
+    FATHMM => "FATHMM prediction (score)",
+  };
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  # only for missense variants
+  return {} unless grep {$_->SO_term eq 'missense_variant'} @{$tva->get_all_OverlapConsequences};
+  
+  # configure command
+  my $command      = $self->{command};
+  $command        =~ m/(\s.+)\/.+/;
+  my $command_dir  = $1;
+  
+  # configure tmp dir and in/out files for FATHMM
+  my $tmp_dir      = $self->{config}->{tmpdir};
+  my $tmp_in_file  = $tmp_dir."/fathmm_$$\.in";
+  my $tmp_out_file = $tmp_dir."/fatmm_$$\.out";
+  
+  # get required input data from TVA
+  my $protein   = $tva->transcript->{_protein} || $tva->transcript->translation->stable_id;
+  my $aa_change = $tva->pep_allele_string;
+  my $aa_pos    = $tva->transcript_variation->translation_start;
+  $aa_change   =~ s/\//$aa_pos/;
+  
+  # check we have valid strings
+  return {} unless $protein && $aa_change =~ /^[A-Z]\d+[A-Z]$/;
+  
+  # write input file
+  open IN, ">$tmp_in_file" or die "ERROR: Could not write to file $tmp_in_file\n";
+  print IN "$protein $aa_change\n";
+  close IN;
+  
+  # run command
+  my $fathmm_err = `cd $command_dir; $command $tmp_in_file $tmp_out_file;`;
+  
+  # read output file
+  open OUT, $tmp_out_file or die "ERROR: Could not read from file $tmp_out_file\n";
+  
+  my ($pred, $score);
+  while(<OUT>) {
+    next if /^\#/;
+    chomp;
+    my @data = split;
+    ($pred, $score) = ($data[4], $data[5]);
+  }
+  close OUT;
+  
+  # delete temporary files
+  unlink($tmp_in_file, $tmp_out_file);
+  
+  return $pred && $score ? {
+    FATHMM => "$pred($score)",
+  } : {};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/FATHMM_MKL.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,128 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ FATHMM_MKL
+
+=head1 SYNOPSIS
+
+ mv FATHMM_MKL.pm ~/.vep/Plugins
+ ./vep -i input.vcf --plugin FATHMM_MKL,fathmm-MKL_Current.tab.gz
+
+=head1 DESCRIPTION
+
+ A VEP plugin that retrieves FATHMM-MKL scores for variants from a tabix-indexed
+ FATHMM-MKL data file.
+ 
+ See https://github.com/HAShihab/fathmm-MKL for details.
+
+ NB: The currently available data file is for GRCh37 only.
+ 
+=cut
+
+package FATHMM_MKL;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+
+  $self->expand_left(0);
+  $self->expand_right(0);
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Feature','Intergenic'];
+}
+
+sub get_header_info {
+  my $self = shift;
+  return {
+    FATHMM_MKL_C => 'FATHMM-MKL coding score',
+    FATHMM_MKL_NC => 'FATHMM-MKL non-coding score',
+  }
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  my $vf = $tva->variation_feature;
+
+  return {} unless $vf->{start} eq $vf->{end};
+  
+  # get allele, reverse comp if needed
+  my $allele = $tva->variation_feature_seq;
+  reverse_comp(\$allele) if $vf->{strand} < 0;
+  
+  return {} unless $allele =~ /^[ACGT]$/;
+  
+  # adjust coords, file is BED-like (but not 0-indexed, go figure...)
+  my ($s, $e) = ($vf->{start}, $vf->{end} + 1);
+  
+  foreach my $data(@{$self->get_data($vf->{chr}, $s, $e)}) {
+    if($data->{start} == $s && $allele eq $data->{alt}) {
+      return $data->{result};
+    }
+  }
+
+  return {};
+}
+
+sub parse_data {
+  my ($self, $line) = @_;
+
+  my ($c, $s, $e, $ref, $alt, $nc_score, $nc_groups, $c_score, $c_groups) = split /\t/, $line;
+
+  return {
+    start => $s,
+    end => $e - 1,
+    alt => $alt,
+    result => {
+      FATHMM_MKL_C  => $c_score,
+      FATHMM_MKL_NC => $nc_score,
+    }
+  };
+}
+
+sub get_start {
+  return $_[1]->{start};
+}
+
+sub get_end {
+  return $_[1]->{end};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/G2P.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,1353 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ G2P
+
+=head1 SYNOPSIS
+
+ mv G2P.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin G2P,file=/path/to/G2P.csv.gz
+
+=head1 DESCRIPTION
+
+ A VEP plugin that uses G2P allelic requirements to assess variants in genes
+ for potential phenotype involvement.
+
+ The plugin has multiple configuration options, though minimally requires only
+ the CSV file of G2P data.
+
+ Options are passed to the plugin as key=value pairs, (defaults in parentheses):
+
+ file                  : path to G2P data file, as found at http://www.ebi.ac.uk/gene2phenotype/downloads
+
+ af_monoallelic        : maximum allele frequency for inclusion for monoallelic genes (0.0001)
+
+ af_biallelic          : maximum allele frequency for inclusion for biallelic genes (0.005)
+ all_confidence_levels : set value to 1 to include all confidence levels: confirmed, probable and possible. 
+                         Default levels are confirmed and probable. 
+ af_keys               : reference populations used for annotating variant alleles with observed
+                         allele frequencies. Allele frequencies are stored in VEP cache files. 
+                         Default populations are:
+                         ESP: AA, EA
+                         1000 Genomes: AFR, AMR, EAS, EUR, SAS 
+                         gnomAD exomes: gnomAD, gnomAD_AFR, gnomAD_AMR, gnomAD_ASJ, gnomAD_EAS, gnomAD_FIN, gnomAD_NFE, gnomAD_OTH, gnomAD_SAS 
+                         Separate multiple values with '&'
+ af_from_vcf           : set value to 1 to include allele frequencies from VCF file. 
+                         Specifiy the list of reference populations to include with --af_from_vcf_keys    
+ af_from_vcf_keys      : reference populations used for annotating variant alleles with observed
+                         allele frequencies. Allele frequencies are retrieved from VCF files. If
+                         af_from_vcf is set to 1 but no populations specified with --af_from_vcf_keys
+                         all available reference populations are included. 
+                         TOPmed: TOPMed
+                         UK10K: ALSPAC, TWINSUK
+                         gnomAD exomes: gnomADe:AFR, gnomADe:ALL, gnomADe:AMR, gnomADe:ASJ, gnomADe:EAS, gnomADe:FIN, gnomADe:NFE, gnomADe:OTH, gnomADe:SAS
+                         gnomAD genomes: gnomADg:AFR, gnomADg:ALL, gnomADg:AMR, gnomADg:ASJ, gnomADg:EAS, gnomADg:FIN, gnomADg:NFE, gnomADg:OTH
+                         Separate multiple values with '&'
+ default_af            : default frequency of the input variant if no frequency data is
+                         found (0). This determines whether such variants are included;
+                         the value of 0 forces variants with no frequency data to be
+                         included as this is considered equivalent to having a frequency
+                         of 0. Set to 1 (or any value higher than af) to exclude them.
+ types                 : SO consequence types to include. Separate multiple values with '&'
+                         (splice_donor_variant,splice_acceptor_variant,stop_gained,
+                         frameshift_variant,stop_lost,initiator_codon_variant,
+                         inframe_insertion,inframe_deletion,missense_variant,
+                         coding_sequence_variant,start_lost,transcript_ablation,
+                         transcript_amplification,protein_altering_variant)
+  
+  log_dir              : write stats to log files in log_dir 
+
+  txt_report           : write all G2P complete genes and attributes to txt file
+
+  html_report          : write all G2P complete genes and attributes to html file
+
+ Example:
+
+ --plugin G2P,file=G2P.csv,af_monoallelic=0.05,af_keys=AA&gnomAD_ASJ,types=stop_gained&frameshift_variant
+ --plugin G2P,file=G2P.csv,af_monoallelic=0.05,types=stop_gained&frameshift_variant
+ --plugin G2P,file=G2P.csv,af_monoallelic=0.05,af_from_vcf=1
+ --plugin G2P,file=G2P.csv
+ 
+=cut
+
+package G2P;
+
+use strict;
+use warnings;
+
+use Cwd;
+use Scalar::Util qw(looks_like_number);
+use FileHandle;
+use Text::CSV;
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+my %DEFAULTS = (
+
+  # vars must have a frequency <= to this to pass
+  af => 0.001,
+  af_monoallelic => 0.0001,
+  af_biallelic => 0.005, 
+
+  af_keys => [qw(AA AFR AMR EA EAS EUR SAS gnomAD gnomAD_AFR gnomAD_AMR gnomAD_ASJ gnomAD_EAS gnomAD_FIN gnomAD_NFE gnomAD_OTH gnomAD_SAS)],
+
+  af_from_vcf_keys => [qw(ALSPAC TOPMed TWINSUK gnomADe:AFR gnomADe:ALL gnomADe:AMR gnomADe:ASJ gnomADe:EAS gnomADe:FIN gnomADe:NFE gnomADe:OTH gnomADe:SAS gnomADg:AFR gnomADg:ALL gnomADg:AMR gnomADg:ASJ gnomADg:EAS gnomADg:FIN gnomADg:NFE gnomADg:OTH)],
+
+  # if no MAF data is found, default to 0
+  # this means absence of MAF data is considered equivalent to MAF=0
+  # set to 1 to do the "opposite", i.e. exclude variants with no MAF data
+  default_af => 0,
+
+  confidence_levels => [qw(confirmed probable)],
+
+  # only include variants with these consequence types
+  # currently not ontology-resolved, exact term matches only
+  types => {map {$_ => 1} qw(splice_donor_variant splice_acceptor_variant stop_gained frameshift_variant stop_lost initiator_codon_variant inframe_insertion inframe_deletion missense_variant coding_sequence_variant start_lost transcript_ablation transcript_amplification protein_altering_variant)},
+
+);
+
+my $af_key_2_population_name = {
+  minor_allele_freq => 'global allele frequency (AF) from 1000 Genomes Phase 3 data',
+  AFR => '1000GENOMES:phase_3:AFR',
+  AMR => '1000GENOMES:phase_3:AMR',
+  EAS => '1000GENOMES:phase_3:EAS',
+  EUR => '1000GENOMES:phase_3:EUR',
+  SAS => '1000GENOMES:phase_3:SAS',
+  AA => 'Exome Sequencing Project 6500:African_American',
+  EA => 'Exome Sequencing Project 6500:European_American',
+  gnomAD => 'Genome Aggregation Database:Total',
+  gnomAD_AFR => 'Genome Aggregation Database exomes:African/African American',
+  gnomAD_AMR => 'Genome Aggregation Database exomes:Latino',
+  gnomAD_ASJ => 'Genome Aggregation Database exomes:Ashkenazi Jewish',
+  gnomAD_EAS => 'Genome Aggregation Database exomes:East Asian',
+  gnomAD_FIN => 'Genome Aggregation Database exomes:Finnish',
+  gnomAD_NFE => 'Genome Aggregation Database exomes:Non-Finnish European',
+  gnomAD_OTH => 'Genome Aggregation Database exomes:Other (population not assigned)',
+  gnomAD_SAS => 'Genome Aggregation Database exomes:South Asian',
+  ALSPAC => 'UK10K:ALSPAC cohort',
+  TOPMed => 'Trans-Omics for Precision Medicine (TOPMed) Program',
+  TWINSUK => 'UK10K:TWINSUK cohort',
+  'gnomADe:AFR' => 'Genome Aggregation Database exomes v170228',
+  'gnomADe:ALL' => 'Genome Aggregation Database exomes v170228',
+  'gnomADe:AMR' => 'Genome Aggregation Database exomes v170228',
+  'gnomADe:ASJ' => 'Genome Aggregation Database exomes v170228',
+  'gnomADe:EAS' => 'Genome Aggregation Database exomes v170228',
+  'gnomADe:FIN' => 'Genome Aggregation Database exomes v170228',
+  'gnomADe:NFE' => 'Genome Aggregation Database exomes v170228',
+  'gnomADe:OTH' => 'Genome Aggregation Database exomes v170228',
+  'gnomADe:SAS' => 'Genome Aggregation Database exomes v170228',
+  'gnomADg:AFR' => 'Genome Aggregation Database genomes v170228:African/African American',
+  'gnomADg:ALL' => 'Genome Aggregation Database genomes v170228:All gnomAD genomes individuals',
+  'gnomADg:AMR' => 'Genome Aggregation Database genomes v170228:Latino',
+  'gnomADg:ASJ' => 'Genome Aggregation Database genomes v170228:Ashkenazi Jewish',
+  'gnomADg:EAS' => 'Genome Aggregation Database genomes v170228:East Asian',
+  'gnomADg:FIN' => 'Genome Aggregation Database genomes v170228:Finnish',
+  'gnomADg:NFE' => 'Genome Aggregation Database genomes v170228:Non-Finnish European',
+  'gnomADg:OTH' => 'Genome Aggregation Database genomes v170228:Other (population not assigned)',
+};
+
+my $allelic_requirements = {
+  'biallelic' => { af => 0.005, rules => {HET => 2, HOM => 1} },
+  'monoallelic' => { af => 0.0001, rules => {HET => 1, HOM => 1} },
+  'hemizygous' => { af => 0.0001, rules => {HET => 1, HOM => 1} },
+  'x-linked dominant' => { af => 0.0001, rules => {HET => 1, HOM => 1} },
+  'x-linked over-dominance' => { af => 0.0001, rules => {HET => 1, HOM => 1} },
+};
+
+my @allelic_requirement_terms = keys %$allelic_requirements;
+
+my @population_wide = qw(minor_allele_freq AA AFR ALSPAC AMR EA EAS EUR SAS TOPMed TWINSUK gnomAD gnomAD_AFR gnomAD_AMR gnomAD_ASJ gnomAD_EAS gnomAD_FIN gnomAD_NFE gnomAD_OTH gnomAD_SAS gnomADe:AFR gnomADe:ALL gnomADe:AMR gnomADe:ASJ gnomADe:EAS gnomADe:FIN gnomADe:NFE gnomADe:OTH gnomADe:SAS gnomADg:AFR gnomADg:ALL gnomADg:AMR gnomADg:ASJ gnomADg:EAS gnomADg:FIN gnomADg:NFE gnomADg:OTH);
+
+sub new {
+  my $class = shift;
+
+  my $self = $class->SUPER::new(@_);
+  
+  my $supported_af_keys = { map {$_ => 1} @population_wide }; 
+
+  my $params = $self->params_to_hash();
+  my $file = '';
+
+  # user only supplied file as first param?
+  if (!keys %$params) {
+    $file = $self->params->[0];
+  }
+  else {
+    $file = $params->{file};
+
+    # process types
+    if ($params->{types}) {
+      $params->{types} = {map {$_ => 1} split(/[\;\&\|]/, $params->{types})};
+    }
+
+    # check af
+    foreach my $af (qw/af_monoallelic af_biallelic/) {
+      if($params->{$af}) {
+        die("ERROR: Invalid value for af: ".$params->{$af} . "\n") unless
+          looks_like_number($params->{$af}) && ($params->{$af} >= 0 && $params->{$af} <= 1)
+      }
+    }
+
+    my $assembly =  $self->{config}->{assembly};
+    my $af_from_vcf_key_2_collection_id = {
+      ALSPAC => {GRCh37 => 'uk10k_GRCh37', GRCh38 => 'uk10k_GRCh38'},
+      TOPMed => {GRCh37 => 'topmed_GRCh37', GRCh38 => 'topmed_GRCh38'},
+      TWINSUK =>  {GRCh37 => 'uk10k_GRCh37', GRCh38 => 'uk10k_GRCh38'},
+      'gnomADe:AFR' => {GRCh37 => 'gnomADe_GRCh37', GRCh38 => 'gnomADe_GRCh38'},
+      'gnomADe:ALL' => {GRCh37 => 'gnomADe_GRCh37', GRCh38 => 'gnomADe_GRCh38'},
+      'gnomADe:AMR' => {GRCh37 => 'gnomADe_GRCh37', GRCh38 => 'gnomADe_GRCh38'},
+      'gnomADe:ASJ' => {GRCh37 => 'gnomADe_GRCh37', GRCh38 => 'gnomADe_GRCh38'},
+      'gnomADe:EAS' => {GRCh37 => 'gnomADe_GRCh37', GRCh38 => 'gnomADe_GRCh38'},
+      'gnomADe:FIN' => {GRCh37 => 'gnomADe_GRCh37', GRCh38 => 'gnomADe_GRCh38'},
+      'gnomADe:NFE' => {GRCh37 => 'gnomADe_GRCh37', GRCh38 => 'gnomADe_GRCh38'},
+      'gnomADe:OTH' => {GRCh37 => 'gnomADe_GRCh37', GRCh38 => 'gnomADe_GRCh38'},
+      'gnomADe:SAS' => {GRCh37 => 'gnomADe_GRCh37', GRCh38 => 'gnomADe_GRCh38'},
+      'gnomADg:AFR' => {GRCh37 => 'gnomADg_GRCh37', GRCh38 => 'gnomADg_GRCh38'},
+      'gnomADg:ALL' => {GRCh37 => 'gnomADg_GRCh37', GRCh38 => 'gnomADg_GRCh38'},
+      'gnomADg:AMR' => {GRCh37 => 'gnomADg_GRCh37', GRCh38 => 'gnomADg_GRCh38'},
+      'gnomADg:ASJ' => {GRCh37 => 'gnomADg_GRCh37', GRCh38 => 'gnomADg_GRCh38'},
+      'gnomADg:EAS' => {GRCh37 => 'gnomADg_GRCh37', GRCh38 => 'gnomADg_GRCh38'},
+      'gnomADg:FIN' => {GRCh37 => 'gnomADg_GRCh37', GRCh38 => 'gnomADg_GRCh38'},
+      'gnomADg:NFE' => {GRCh37 => 'gnomADg_GRCh37', GRCh38 => 'gnomADg_GRCh38'},
+      'gnomADg:OTH' => {GRCh37 => 'gnomADg_GRCh37', GRCh38 => 'gnomADg_GRCh38'},
+    };
+
+    my @keys = ();
+    my $vcf_collection_ids = {};
+    if ($params->{af_keys}) {
+      push @keys, $params->{af_keys};
+    } else {
+      push @keys, @{$DEFAULTS{af_keys}};
+    }
+    if ($params->{af_from_vcf}) {
+      if ($params->{af_from_vcf_keys}) {
+        push @keys, $params->{af_from_vcf_keys};
+      } else {
+        push @keys, @{$DEFAULTS{af_from_vcf_keys}};
+      }
+    }
+    
+    my @af_keys = ();
+    foreach my $af_key_set (@keys) {
+      foreach my $af_key (split(/[\;\&\|]/, $af_key_set)) {
+        die("ERROR: af_key: " . $af_key . " not supported. Check plugin documentation for supported af_keys.\n") unless $supported_af_keys->{$af_key};
+        push @af_keys, $af_key;
+        if ($af_from_vcf_key_2_collection_id->{$af_key}) {
+          
+          $vcf_collection_ids->{$af_from_vcf_key_2_collection_id->{$af_key}->{$assembly}} = 1;
+        }
+      }
+    }
+    $params->{af_keys} = \@af_keys;
+    $params->{vcf_collection_ids} = $vcf_collection_ids;
+  }
+
+  my ($sec, $min, $hour, $mday, $mon, $year, $wday, $yday, $isdst) = localtime(time);
+  $year += 1900;
+  $mon++;
+  my $stamp = join('_', ($year, $mon, $mday, $hour, $min));
+  my $cwd_dir = getcwd;
+  my $new_log_dir = "$cwd_dir/g2p_log_dir\_$stamp";
+  my $log_dir = $params->{log_dir} || $new_log_dir;
+  if (-d $log_dir) {
+    my @files = <$log_dir/*>;
+    if (scalar @files > 0) {
+      unlink glob "'$log_dir/*.*'";
+    }
+    @files = <$log_dir/*>;
+    if (scalar @files > 0) {
+      mkdir $new_log_dir, 0755;
+      $params->{log_dir} = $new_log_dir;
+    }
+  } else {
+    mkdir $log_dir, 0755;
+    $params->{log_dir} = $log_dir;
+  }
+
+  foreach my $report_type (qw/txt_report html_report/) {
+    if (!$params->{$report_type}) {
+      my $file_type = ($report_type eq 'txt_report') ? 'txt' : 'html';
+      $params->{$report_type} = $cwd_dir . "/$report_type\_$stamp.$file_type";
+    } 
+  }
+
+  if ($params->{all_confidence_levels}) {
+    push @{$params->{confidence_levels}}, 'possible', @{$DEFAULTS{confidence_levels}};
+  }
+
+  # copy in default params
+  $params->{$_} //= $DEFAULTS{$_} for keys %DEFAULTS;
+  $self->{user_params} = $params;
+
+  if (!defined($self->{config}->{reg})) {
+    my $reg = 'Bio::EnsEMBL::Registry';
+    $reg->load_registry_from_db(
+      -host       => $self->config->{host},
+      -user       => $self->config->{user},
+      -port       => $self->config->{port},
+      -db_version => $self->config->{db_version},
+      -species    => $self->config->{species},
+      -no_cache   => $self->config->{no_slice_cache},
+    );
+    $self->{config}->{reg} = $reg;
+  }
+
+  my $va = $self->{config}->{reg}->get_adaptor($self->{config}->{species}, 'variation', 'variation');
+  $va->db->use_vcf(1);
+  $va->db->include_failed_variations(1);
+  $self->{config}->{va} = $va;
+  my $pa = $self->{config}->{reg}->get_adaptor($self->{config}->{species}, 'variation', 'population');
+  $self->{config}->{pa} = $pa;
+  my $vca = $self->{config}->{reg}->get_adaptor($self->{config}->{species}, 'variation', 'VCFCollection');
+  $self->{config}->{vca} = $vca;
+  my $ta = $self->{config}->{reg}->get_adaptor($self->{config}->{species}, 'core', 'transcript');
+  $self->{config}->{ta} = $ta;
+
+  # read data from file
+  $self->{gene_data} = $self->read_gene_data_from_file($file);
+  $self->synonym_mappings();
+
+  # force some config params
+  $self->{config}->{individual} //= ['all'];
+  $self->{config}->{symbol} = 1;
+
+  $self->{config}->{check_existing} = 1;
+  $self->{config}->{failed} = 1;
+  $self->{config}->{af} = 1;
+  $self->{config}->{af_1kg} = 1;
+  $self->{config}->{af_esp} = 1;
+  $self->{config}->{af_gnomad} = 1;
+#  $self->{config}->{sift} = 'b';
+#  $self->{config}->{polyphen} = 'b';
+#  $self->{config}->{hgvsc} = 1;
+#  $self->{config}->{hgvsp} = 1;
+
+  # tell VEP we have a cache so stuff gets shared/merged between forks
+  $self->{has_cache} = 1;
+  $self->{cache}->{g2p_in_vcf} = {};
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  my $self = shift;
+
+  return {
+    G2P_flag => 'Flags zygosity of valid variants for a G2P gene',
+    G2P_complete => 'Indicates this variant completes the allelic requirements for a G2P gene',
+    G2P_gene_req => 'MONO or BI depending on the context in which this gene has been explored',
+  };
+}
+
+sub run {
+  my ($self, $tva, $line) = @_;
+
+  # only interested if we know the zygosity
+  my $zyg = $line->{Extra}->{ZYG} || $line->{ZYG};
+  return {} unless $zyg;
+
+  # only interested in given gene set
+  my $tr = $tva->transcript;
+
+  my $ensembl_gene_id = $tr->{_gene}->stable_id;
+  my $gene_symbol = $tr->{_gene_symbol} || $tr->{_gene_hgnc};
+  return {} unless $gene_symbol;
+  my $gene_data = $self->gene_data($gene_symbol);
+  if (! defined $gene_data) {
+    my $ensembl_gene_id = $tr->{_gene}->stable_id;
+    $gene_data = $self->gene_data($ensembl_gene_id);
+  }
+
+  if (!$self->{cache}->{g2p_in_vcf}->{$gene_symbol}) {
+    $self->write_report('G2P_in_vcf', $gene_symbol);
+    $self->{cache}->{g2p_in_vcf}->{$gene_symbol} = 1;
+  }
+  return {} unless defined $gene_data;
+
+  my @ars = ($gene_data->{'allelic requirement'}) ? @{$gene_data->{'allelic requirement'}} : ();
+  my %seen;
+  @ars = grep { !$seen{$_}++ } @ars;
+
+  return {} unless (@ars && ( grep { exists($allelic_requirements->{$_}) } @ars));
+  # limit by type
+  my @consequence_types = map { $_->SO_term } @{$tva->get_all_OverlapConsequences};
+
+  return {} unless grep {$self->{user_params}->{types}->{$_->SO_term}} @{$tva->get_all_OverlapConsequences};
+
+  # limit by MAF
+  my $threshold = 0; 
+  my ($freqs, $existing_variant, $ar_passed) = @{$self->get_freq($tva, \@ars)};
+
+  return {} if (!keys %$ar_passed);
+
+  my $vf = $tva->base_variation_feature;
+  my $allele = $tva->variation_feature_seq;
+  my $start = $vf->{start};
+  my $end = $vf->{end};
+
+  my $individual = $vf->{individual};
+  my $vf_name = $vf->variation_name;
+  if ($vf_name || $vf_name eq '.') {
+    $vf_name = ($vf->{original_chr} || $vf->{chr}) . '_' . $vf->{start} . '_' . ($vf->{allele_string} || $vf->{class_SO_term});
+  }
+  my $allele_string = $vf->{allele_string};
+  my @alleles = split('/', $allele_string);
+  my $ref = $alleles[0]; 
+  my $seq_region_name = $vf->{chr};
+
+  my $params = $self->{user_params};
+  my $refseq = $tr->{_refseq} || 'NA';
+  my $tr_stable_id = $tr->stable_id;
+  my $hgvs_t = $tva->hgvs_transcript || 'NA';
+  my $hgvs_p = $tva->hgvs_protein || 'NA';
+  
+  my ($clin_sig, $novel, $failed, $frequencies, $existing_name) = ('NA', 'yes', 'NA', 'NA', 'NA');
+  if ($existing_variant) {
+    $clin_sig = $existing_variant->{clin_sig} || 'NA';
+    $failed = ($existing_variant->{failed}) ? 'yes' : 'no';
+    $existing_name = $existing_variant->{variation_name} || 'NA';
+    $novel = 'no';
+  }
+
+  my $pph_score   = (defined $tva->polyphen_score) ? $tva->polyphen_score : 'NA';
+  my $pph_pred    = (defined $tva->polyphen_prediction) ? $tva->polyphen_prediction : 'NA';
+  my $sift_score  = (defined $tva->sift_score) ? $tva->sift_score : 'NA';
+  my $sift_pred   = (defined $tva->sift_prediction) ? $tva->sift_prediction : 'NA';
+ 
+  if (scalar keys %$freqs > 0) {
+    $frequencies = join(',', map {"$_=$freqs->{$_}"} keys %$freqs);
+  }   
+ 
+  my $ar = join(',', sort keys %$ar_passed);
+  my $ar_in_g2pdb = join(',', sort @ars);
+  my $g2p_data = {
+    'zyg' => $zyg,
+    'allele_requirement' => $ar,
+    'ar_in_g2pdb' => $ar_in_g2pdb,
+    'frequencies' => $frequencies,
+    'consequence_types' => join(',', @consequence_types),
+    'refseq' => $refseq,
+    'failed' => $failed,
+    'clin_sig' => $clin_sig, 
+    'novel' => $novel,
+    'existing_name' => $existing_name,
+    'hgvs_t' => $hgvs_t,
+    'hgvs_p' => $hgvs_p,
+    'vf_location' => "$seq_region_name:$start-$end $ref/$allele",
+    'sift_score' => "$sift_score",
+    'sift_prediction' => $sift_pred,
+    'polyphen_score' => "$pph_score",
+    'polyphen_prediction' => $pph_pred,
+  };
+
+  my %return = (
+    G2P_flag => $zyg
+  );
+
+
+  $self->write_report('G2P_flag', $gene_symbol, $tr_stable_id, $individual, $vf_name, $g2p_data);
+
+  $self->write_report('G2P_complete', $gene_symbol, $tr_stable_id, $individual, $vf_name, $ar, $zyg);
+
+  my $cache = $self->{cache}->{$individual}->{$tr->stable_id} ||= {};
+
+  delete $cache->{$vf_name} if exists($cache->{$vf_name});
+
+  # biallelic genes require >=1 hom or >=2 hets
+
+  my $gene_reqs = {};
+
+  foreach my $ar (keys %$ar_passed) { 
+    if($ar eq 'biallelic') {
+      # homozygous, report complete
+      if(uc($zyg) eq 'HOM') {
+        $return{G2P_complete} = 1;
+        $gene_reqs->{BI} = 1;
+      }
+      # heterozygous
+      # we need to cache that we've observed one
+      elsif(uc($zyg) eq 'HET') {
+        if(scalar keys %$cache) {
+          $return{G2P_complete} = 1;
+        }
+        $cache->{$vf_name} = 1;
+      }
+    }
+    # monoallelic genes require only one allele
+    elsif($ar eq 'monoallelic' || $ar eq 'x-linked dominant' || $ar eq 'hemizygous' || $ar eq 'x-linked over-dominance') {
+      $return{G2P_complete} = 1;
+      $gene_reqs->{MONO} = 1;
+    }
+    else {
+      return {};
+    }
+  }
+  if ($return{G2P_complete}) {
+    $return{G2P_gene_req} = join(',', sort keys %$gene_reqs);
+  }
+
+  return \%return;
+}
+
+# read G2P CSV dump
+# as from http://www.ebi.ac.uk/gene2phenotype/downloads
+sub read_gene_data_from_file {
+  my $self = shift;
+  my $file = shift;
+  my $delimiter = shift;
+  my (@headers, %gene_data);
+
+  my $assembly =  $self->{config}->{assembly};
+  die("ERROR: No file specified or could not read from file ".($file || '')."\n") unless $file && -e $file;
+
+  my @confidence_levels = @{$self->{user_params}->{confidence_levels}}, "\n";
+
+  # determine file type
+  my $file_type;
+  my $fh = FileHandle->new($file, 'r');
+  while (<$fh>) {
+    chomp;
+      if (/Model_Of_Inheritance/) {
+        $file_type = 'panelapp';
+      } elsif (/"allelic requirement"/) {
+        $file_type = 'g2p';
+      } else {
+        $file_type = 'unknown';
+      }
+      last;
+  }
+  $fh->close();
+  if ($file_type eq 'unknown') {
+    if ($file =~ /gz$/) { 
+      die("ERROR: G2P plugin can only read uncompressed data");
+    } else {
+      die("ERROR: Could not recognize input file format. Format must be one of panelapp, g2p or custom. Check website for details: https://www.ebi.ac.uk/gene2phenotype/g2p_vep_plugin");
+    }
+  }
+
+  if ($file_type eq 'panelapp') {
+    my @headers = ();
+    my $csv = Text::CSV->new ({ sep_char => "\t" });
+    open my $fh, "<:encoding(utf8)", "$file" or die "$file: $!";
+    while ( my $row = $csv->getline( $fh ) ) {
+      unless (@headers) {
+        @headers = @$row;
+      } else {
+        my %tmp = map {$headers[$_] => $row->[$_]} (0..$#headers);
+        my $gene_symbol = $tmp{"Gene Entity Symbol"};
+        my $ensembl_gene_id = "";
+        if ($assembly eq 'GRCh37') { 
+          $ensembl_gene_id = $tmp{"EnsemblId(GRch37)"};
+        } else { # GRCh38
+          $ensembl_gene_id = $tmp{"EnsemblId(GRch38)"};
+        }
+        if ($ensembl_gene_id) {
+          my @ars = ();
+          my $allelic_requirement_panel_app = $tmp{"Model_Of_Inheritance"};
+          if ($allelic_requirement_panel_app =~ m/MONOALLELIC|BOTH/) {
+            push @ars, 'monoallelic';
+          } elsif ($allelic_requirement_panel_app =~ m/BIALLELIC|BOTH/) {
+            push @ars, 'biallelic';
+          } elsif ($allelic_requirement_panel_app eq 'X-LINKED: hemizygous mutation in males, biallelic mutations in females') {
+            push @ars, 'hemizygous';
+          } elsif ($allelic_requirement_panel_all eq 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)') {
+            push @ars, 'x-linked dominant';
+          } else {
+            $self->write_report('log', "no allelelic_requirement for $ensembl_gene_id");
+          }
+          foreach my $ar (@ars) {
+            push @{$gene_data{$ensembl_gene_id}->{"allelic requirement"}}, $ar;
+          }
+        } else {
+          $self->write_report('log', "no ensembl gene id for $gene_symbol");
+        }
+      }
+    }
+    $csv->eof or $csv->error_diag();
+    close $fh;
+  }
+
+  if ($file_type eq 'g2p') {
+    # this regexp allows for nested ",", e.g.
+    # item,description
+    # cheese,"salty,delicious"
+    my $re = qr/(?: "\( ( [^()""]* ) \)" |  \( ( [^()]* ) \) |  " ( [^"]* ) " |  ( [^,]* ) ) , \s* /x;
+
+    my $fh = FileHandle->new($file, 'r');
+
+    while(<$fh>) {
+      chomp;
+      $_ =~ s/\R//g;
+      my @split = grep defined, "$_," =~ /$re/g;
+      unless(@headers) {
+        if ($file_type eq 'g2p') {
+          @headers = map {s/\"//g; $_} @split;
+        } else {
+          @headers = @split;
+        }
+      }
+      else {
+        my %tmp = map {$headers[$_] => $split[$_]} (0..$#split);
+        die("ERROR: Gene symbol column not found\n$_\n") unless $tmp{"gene symbol"};
+        my $confidence_value = $tmp{"DDD category"};
+        next if (!grep{$_ eq $confidence_value} @confidence_levels);
+        my $gene_symbol = $tmp{"gene symbol"};
+        $gene_data{$gene_symbol}->{"prev symbols"} = $tmp{"prev symbols"};
+        push @{$gene_data{$gene_symbol}->{"allelic requirement"}}, $tmp{"allelic requirement"} if ($tmp{"allelic requirement"});
+        $self->write_report('G2P_list', $tmp{"gene symbol"}, $tmp{"DDD category"});
+      }
+    }
+    $fh->close;
+  }
+  return \%gene_data;
+}
+
+# return either whole gene data hash or one gene's data
+# this should allow updates to this plugin to e.g. query a REST server, for example
+sub gene_data {
+  my ($self, $gene_symbol) = @_;
+  my $gene_data = $self->{gene_data}->{$gene_symbol};
+  if (!$gene_data) {
+    my $prev_gene_symbol = $self->{prev_symbol_mappings}->{$gene_symbol};
+    return $prev_gene_symbol ? $self->{gene_data}->{$prev_gene_symbol} : undef;
+  } 
+  return $gene_data;
+}
+
+sub synonym_mappings {
+  my $self = shift;
+  my $gene_data = $self->{gene_data};
+  my $synonym_mappings = {};
+  foreach my $gene_symbol (keys %$gene_data) {
+    my $prev_symbols = $gene_data->{$gene_symbol}->{'prev symbols'};
+    if ($prev_symbols) {
+      foreach my $prev_symbol (split(';', $prev_symbols)) {
+        $synonym_mappings->{$prev_symbol} = $gene_symbol;
+      }
+    }
+  }
+  $self->{prev_symbol_mappings} = $synonym_mappings;
+}
+
+sub get_freq {
+  my $self = shift;
+  my $tva = shift;
+  my $ars = shift;
+  my $allele = $tva->variation_feature_seq;
+  my $vf     = $tva->base_variation_feature;
+  reverse_comp(\$allele) if $vf->{strand} < 0;
+  my $vf_name = $vf->variation_name;
+  if ($vf_name || $vf_name eq '.') {
+    $vf_name = ($vf->{original_chr} || $vf->{chr}) . '_' . $vf->{start} . '_' . ($vf->{allele_string} || $vf->{class_SO_term});
+  }
+  my $cache = $self->{cache}->{$vf_name}->{_g2p_freqs} ||= {};
+
+  if (exists $cache->{$allele}->{failed}) {
+    return [$cache->{$allele}->{freq}, $cache->{$allele}->{ex_variant}, {}];
+  }
+
+  if (exists $cache->{$allele}->{freq}) {
+    return [$cache->{$allele}->{freq}, $cache->{$allele}->{ex_variant}, $cache->{$allele}->{passed_ar}];
+  }
+
+  if (!$vf->{existing}) {
+    my $failed_ars = {};
+    my $freqs = {};
+    my $passed = $self->frequencies_from_VCF($freqs, $vf, $allele, $ars, $failed_ars);
+    if (!$passed) {
+      $cache->{$allele}->{failed} = 1;
+      return [{}, {}, {}];
+    } else {
+     $cache->{$allele}->{freq} = $freqs;
+     $cache->{$allele}->{ex_variant} = undef;
+     # if we get to here return all allelic requirements that passed threshold filtering
+     my $passed_ar = {};
+     foreach my $ar (@$ars) {
+      if (!$failed_ars->{$ar}) {
+        $passed_ar->{$ar} = 1;
+      }
+     }
+     $cache->{$allele}->{passed_ar} = $passed_ar;
+     return [$cache->{$allele}->{freq}, $cache->{$allele}->{ex_variant}, $cache->{$allele}->{passed_ar}];
+    }
+  }
+
+  my @existing_variants = @{$vf->{existing}};
+  # favour dbSNP variants
+  my @dbSNP_variants = grep {$_->{variation_name} =~ /^rs/} @existing_variants;
+  if (@dbSNP_variants) {
+    @existing_variants = @dbSNP_variants;
+  }
+  foreach my $ex (@existing_variants) {
+    my $existing_allele_string = $ex->{allele_string};
+    my $variation_name = $ex->{variation_name};
+    my $freqs = {};
+    my $failed_ars = {};
+    foreach my $af_key (@{$self->{user_params}->{af_keys}}) {
+      my $freq = $self->{user_params}->{default_af};
+      if ($af_key eq 'minor_allele_freq') {
+        if (defined $ex->{minor_allele_freq}) {
+          if (($ex->{minor_allele} || '') eq $allele ) {
+            $freq = $ex->{minor_allele_freq};
+          } else {
+            $freq = $self->correct_frequency($tva, $existing_allele_string, $ex->{minor_allele}, $ex->{minor_allele_freq}, $allele, $variation_name, $af_key, $vf_name) || $freq;
+          }
+        }
+      }
+      else {
+        my @pairs = split(',', $ex->{$af_key} || '');
+        my $found = 0;
+        if (scalar @pairs == 0) {
+          $found = 1; # no allele frequency for this population/af_key available
+        }
+        foreach my $pair (@pairs) {
+          my ($a, $f) = split(':', $pair);
+          if(($a || '') eq $allele && defined($f)) {
+            $freq = $f;
+            $found = 1;
+          }
+        }
+        if (!$found) {
+          $freq = $self->correct_frequency($tva, $existing_allele_string, undef, undef, $allele, $variation_name, $af_key, $vf_name) || $freq;
+        }
+      }
+      if (!$self->continue_af_annotation($ars, $failed_ars, $freq)) {
+        # cache failed results
+        $cache->{$allele}->{failed} = 1;
+        return [$cache->{$allele}->{freq}, $cache->{$allele}->{ex_variant}, {}];
+      }
+      $freqs->{$af_key} = $freq if ($freq);
+    }
+    if ($self->{user_params}->{af_from_vcf}) {
+      my $passed = $self->frequencies_from_VCF($freqs, $vf, $allele, $ars, $failed_ars);
+      if (!$passed) {
+        $cache->{$allele}->{failed} = 1;
+        return [$cache->{$allele}->{freq}, $cache->{$allele}->{ex_variant}, {}];
+      }
+    }
+    $cache->{$allele}->{freq} = $freqs;
+    $cache->{$allele}->{ex_variant} = $ex;
+
+    # if we get to here return all allelic requirements that passed threshold filtering
+    my $passed_ar = {};
+    foreach my $ar (@$ars) {
+      if (!$failed_ars->{$ar}) {
+        $passed_ar->{$ar} = 1;
+      }
+    }
+    $cache->{$allele}->{passed_ar} = $passed_ar;
+
+  }
+
+  return [$cache->{$allele}->{freq}, $cache->{$allele}->{ex_variant}, $cache->{$allele}->{passed_ar}];
+}
+
+sub correct_frequency {
+  my ($self, $tva, $allele_string, $minor_allele, $af, $allele, $variation_name, $af_key, $vf_name) = @_;
+
+  my @existing_alleles = split('/', $allele_string);
+  if (!grep( /^$allele$/, @existing_alleles)) {
+    return 0.0;  
+  } 
+
+  if ($af_key eq 'minor_allele_freq' && (scalar @existing_alleles == 2)) {
+    my $existing_ref_allele = $existing_alleles[0];
+    my $existing_alt_allele = $existing_alleles[1];
+    if ( ($minor_allele eq $existing_ref_allele && ($allele eq $existing_alt_allele)) || 
+         ($minor_allele eq $existing_alt_allele && ($allele eq $existing_ref_allele)) ) {
+      return (1.0 - $af);
+    } 
+  } else {
+    my $va = $self->{config}->{va};
+    my $pa = $self->{config}->{pa};
+    my $variation = $va->fetch_by_name($variation_name);
+    my $af_key = $self->{user_params}->{af_keys};
+    my $population_name = $af_key_2_population_name->{$af_key};
+    if ($population_name) {
+      my $population = $self->{config}->{$population_name};
+      if (!$population) {
+        $population = $pa->fetch_by_name($population_name);
+        $self->{config}->{$population_name} = $population;
+      }
+      foreach (@{$variation->get_all_Alleles($population)}) {
+        if ($_->allele eq $allele) {
+          return $_->frequency;
+        }
+      }
+    }
+  }     
+  return 0.0;
+}
+
+sub frequencies_from_VCF {
+  my $self = shift;
+  my $freqs = shift;
+  my $vf = shift;
+  my $vf_allele = shift;
+  my $ars = shift;
+  my $failed_ars = shift;
+  my $vca = $self->{config}->{vca};
+  my $collections = $vca->fetch_all;
+  foreach my $vc (@$collections) {
+    next if (! $self->{user_params}->{vcf_collection_ids}->{$vc->id});
+    my $alleles = $vc->get_all_Alleles_by_VariationFeature($vf);
+    foreach my $allele (@$alleles) {
+      if ($allele->allele eq $vf_allele) {
+        my $af_key = $allele->population->name;
+        my $freq = $allele->frequency;
+        return 0 if (!$self->continue_af_annotation($ars, $failed_ars, $freq));
+        $freqs->{$af_key} = $freq;
+      }
+    }
+  }
+  return 1;
+}
+
+sub continue_af_annotation {
+  my $self = shift;
+  my $ars = shift;
+  my $failed_ars = shift;
+  my $freq = shift;
+  foreach my $ar (@$ars) {
+    if (!$failed_ars->{$ar})  {
+      if (defined $allelic_requirements->{$ar}) {
+        my $threshold = $allelic_requirements->{$ar}->{af};
+        if ($freq > $threshold) {
+          $failed_ars->{$ar} = 1;
+        }
+      }
+    } 
+  }
+  return (scalar @$ars != scalar keys %$failed_ars);
+} 
+
+
+
+sub write_report {
+  my $self = shift;
+  my $flag = shift;
+  my $log_dir = $self->{user_params}->{log_dir};
+  my $log_file = "$log_dir/$$.txt";
+  open(my $fh, '>>', $log_file) or die "Could not open file '$flag $log_file' $!";
+  if ($flag eq 'G2P_list') {
+    my ($gene_symbol, $DDD_category) = @_;
+    $DDD_category ||= 'Not assigned';
+    print $fh "$flag\t$gene_symbol\t$DDD_category\n";
+  } elsif ($flag eq 'G2P_in_vcf') {
+    my $gene_symbol = shift;
+    print $fh "$flag\t$gene_symbol\n";
+  } elsif ($flag eq 'G2P_complete') {
+    print $fh join("\t", $flag, @_), "\n";
+  } elsif ($flag eq 'log') {
+    print $fh join("\t", $flag, @_), "\n";
+  } else {
+    my ($gene_symbol, $tr_stable_id, $individual, $vf_name, $data) = @_;
+    $data = join(';', map {"$_=$data->{$_}"} sort keys %$data);
+    print $fh join("\t", $flag, $gene_symbol, $tr_stable_id, $individual, $vf_name, $data), "\n";
+  }
+  close $fh;
+}
+
+sub finish {
+  my $self = shift;
+  $self->generate_report;
+}
+
+sub generate_report {
+  my $self = shift;
+  my $result_summary = $self->parse_log_files;
+  my $chart_txt_data = $self->chart_and_txt_data($result_summary);
+  my $chart_data = $chart_txt_data->{chart_data};
+  my $txt_data = $chart_txt_data->{txt_data};
+  my $canonical_transcripts = $chart_txt_data->{canonical_transcripts};
+  $self->write_txt_output($txt_data);
+  $self->write_charts($result_summary, $chart_data, $canonical_transcripts);
+}
+
+sub write_txt_output {
+  my $self = shift;
+  my $txt_output_data = shift; 
+  my $txt_output_file = $self->{user_params}->{txt_report};
+  my $fh_txt = FileHandle->new($txt_output_file, 'w');
+  foreach my $individual (sort keys %$txt_output_data) {
+    foreach my $gene_symbol (keys %{$txt_output_data->{$individual}}) {
+      foreach my $ar (keys %{$txt_output_data->{$individual}->{$gene_symbol}}) {
+        foreach my $tr_stable_id (keys %{$txt_output_data->{$individual}->{$gene_symbol}->{$ar}}) {
+          my $is_canonical = $txt_output_data->{$individual}->{$gene_symbol}->{$ar}->{$tr_stable_id}->{is_canonical};
+          my $canonical_tag = ($is_canonical) ? 'is_canonical' : 'not_canonical';
+          my $req =  $txt_output_data->{$individual}->{$gene_symbol}->{$ar}->{$tr_stable_id}->{REQ};
+          my $variants = join(';', @{$txt_output_data->{$individual}->{$gene_symbol}->{$ar}->{$tr_stable_id}->{variants}});
+          print $fh_txt join("\t", $individual, $gene_symbol, $tr_stable_id, $canonical_tag, "OBS=$ar", "REQ=$req", $variants), "\n";
+        }
+      }
+    }
+  }
+  $fh_txt->close();
+}
+
+sub write_charts {
+  my $self = shift;
+  my $result_summary = shift;
+  my $chart_data = shift;
+  my $canonical_transcripts = shift;
+
+  my $count_g2p_genes = keys %{$result_summary->{g2p_list}};
+  my $count_in_vcf_file = keys %{$result_summary->{in_vcf_file}};
+  my $count_complete_genes = scalar keys %{$result_summary->{complete_genes}};
+
+  my @charts = ();
+  my @frequencies_header = (); 
+
+  foreach my $short_name (sort @{$self->{user_params}->{af_keys}}) {
+    my $text = $af_key_2_population_name->{$short_name};
+    push @frequencies_header, "<a style=\"cursor: pointer\" data-placement=\"top\" data-toggle=\"tooltip\" data-container=\"body\" title=\"$text\">$short_name</a>";
+  }
+
+  my $count = 1;
+  my @new_header = (
+    'Variant location and alleles (REF/ALT)',
+    'Variant name', 
+    'Existing name', 
+    'Zygosity', 
+    'All allelic requirements from G2P DB',
+    'Consequence types', 
+    'ClinVar annotation', 
+    'SIFT', 
+    'PolyPhen', 
+    'Novel variant', 
+    'Has been failed by Ensembl', 
+    @frequencies_header,
+    'HGVS transcript', 
+    'HGVS protein', 
+    'RefSeq IDs', 
+  );
+
+  my $html_output_file = $self->{user_params}->{html_report};
+  my $fh_out = FileHandle->new($html_output_file, 'w');
+  print $fh_out stats_html_head(\@charts);
+  print $fh_out "<div class='main_content container'>";
+
+ 
+  print $fh_out "<h1>G2P report</h1>";
+  print $fh_out "<p>Input and output files:</p>";
+
+  print $fh_out "<dl class='dl-horizontal'>";
+  print $fh_out "<dt>G2P list</dt>";
+  print $fh_out "<dd>" . $self->{user_params}->{file} .  "</dd>";
+  print $fh_out "<dt>Log directory</dt>";
+  print $fh_out "<dd>" . $self->{user_params}->{log_dir} .  "</dd>";
+  print $fh_out "<dt>HTML report</dt>";
+  print $fh_out "<dd>" . $self->{user_params}->{html_report} .  "</dd>";
+  print $fh_out "<dt>TXT report</dt>";
+  print $fh_out "<dd>" . $self->{user_params}->{txt_report} .  "</dd>";
+  print $fh_out "</dl>";
+
+  print $fh_out "<p>Counts:</p>";
+  print $fh_out "<dl class='dl-horizontal text-overflow'>";
+  print $fh_out "<dt>$count_g2p_genes</dt>";
+  print $fh_out "<dd>G2P genes</dd>";
+  print $fh_out "<dt>$count_in_vcf_file</dt>";
+  print $fh_out "<dd>G2P genes in input VCF file</dd>";
+  print $fh_out "<dt>$count_complete_genes</dt>";
+  print $fh_out "<dd>G2P complete genes in input VCF file</dd>";
+  print $fh_out "</dl>";
+
+
+  print $fh_out "<h1>Summary of G2P complete genes per individual</h1>";
+  print $fh_out "<p>G2P complete gene: A sufficient number of variant hits for the observed allelic requirement in at least one of the gene's transcripts. Variants are filtered by frequency.</p>";
+  print $fh_out "<p>Frequency thresholds and number of required variant hits for each allelic requirement:</p>";
+
+  print $fh_out "<table class='table table-bordered'>";
+  print $fh_out "<thead>";
+  print $fh_out "<tr><th>Allelic requirement</th><th>Frequency threshold for filtering</th><th>Variant counts by zygosity</th></tr>";
+  print $fh_out "</thead>";
+  print $fh_out "<tbody>";
+  foreach my $ar (sort keys %$allelic_requirements) {
+    my $af = $allelic_requirements->{$ar}->{af};
+    my $rules =  $allelic_requirements->{$ar}->{rules};
+    my $rule = join(' OR ', map {"$_ >= $rules->{$_}"} keys %$rules);
+    print $fh_out "<tr><td>$ar</td><td>$af</td><td>$rule</td></tr>";
+  }
+  print $fh_out "</tbody>";
+  print $fh_out "</table>";
+
+my $switch =<<SHTML;
+<form>
+<div class="checkbox">
+  <label>
+    <input class="target" type="checkbox"> Show only canonical transcript
+  </label>
+</div>
+</form>
+SHTML
+
+  print $fh_out $switch;
+
+  foreach my $individual (sort keys %$chart_data) {
+    foreach my $gene_symbol (keys %{$chart_data->{$individual}}) {
+      foreach my $ar (keys %{$chart_data->{$individual}->{$gene_symbol}}) {
+        print $fh_out "<ul>\n";
+        foreach my $transcript_stable_id (keys %{$chart_data->{$individual}->{$gene_symbol}->{$ar}}) {
+          my $class = ($canonical_transcripts->{$transcript_stable_id}) ? 'is_canonical' : 'not_canonical';
+          print $fh_out "<li><a class=\"$class\" href=\"#$individual\_$gene_symbol\_$ar\_$transcript_stable_id\">" . "$individual &gt; $gene_symbol &gt; $ar &gt; $transcript_stable_id" . "</a> </li>\n";
+        }
+        print $fh_out "</ul>\n";
+      }
+    }
+  }
+
+  foreach my $individual (sort keys %$chart_data) {
+    foreach my $gene_symbol (keys %{$chart_data->{$individual}}) {
+      foreach my $ar (keys %{$chart_data->{$individual}->{$gene_symbol}}) {
+        foreach my $transcript_stable_id (keys %{$chart_data->{$individual}->{$gene_symbol}->{$ar}}) {
+          my $class = ($canonical_transcripts->{$transcript_stable_id}) ? 'is_canonical' : 'not_canonical';
+          print $fh_out "<div class=\"$class\">";
+          my $name = "$individual\_$gene_symbol\_$ar\_$transcript_stable_id";
+          my $title = "$individual &gt; $gene_symbol &gt; $ar &gt; $transcript_stable_id";
+          print $fh_out "<h3><a name=\"$name\"></a>$title <a title=\"Back to Top\" data-toggle=\"tooltip\" href='#top'><span class=\"glyphicon glyphicon-arrow-up\" aria-hidden=\"true\"></span></a></h3>\n";
+          print $fh_out "<div class=\"table-responsive\" style=\"width:100%\">\n";
+          print $fh_out "<TABLE  class=\"table table-bordered table-condensed\" style=\"margin-left: 2em\">";
+          print $fh_out "<thead>\n";
+          print $fh_out "<tr>" . join('', map {"<th>$_</th>"} @new_header) . "</tr>\n";
+          print $fh_out "</thead>\n";
+          print $fh_out "<tbody>\n";
+          foreach my $vf_data (@{$chart_data->{$individual}->{$gene_symbol}->{$ar}->{$transcript_stable_id}}) {
+            my $data_row = $vf_data->[0];
+            my @tds = ();
+            foreach my $cell (@$data_row) {
+              my $value = $cell->[0];
+              my $class = $cell->[1];
+              if ($class) {
+                push @tds, "<td class=\"$class\">$value</td>";
+              } else {
+                push @tds, "<td>$value</td>";
+              }
+            }
+            print $fh_out "<tr>", join('', @tds), "</tr>\n";
+          }
+          print $fh_out "</tbody>\n";
+          print $fh_out "</TABLE>\n";
+          print $fh_out "</div>\n";
+          print $fh_out "</div>\n";
+        }
+      }
+    }
+  }
+  print $fh_out stats_html_tail();
+}
+
+sub chart_and_txt_data {
+  my $self = shift;
+  my $result_summary = shift;
+  my $individuals = $result_summary->{individuals};
+  my $complete_genes = $result_summary->{complete_genes};
+  my $acting_ars = $result_summary->{acting_ars};
+  my $new_order = $result_summary->{new_order};
+
+#  my @frequencies_header = sort keys $af_key_2_population_name;
+  my @frequencies_header = sort @{$self->{user_params}->{af_keys}};
+
+  my $assembly = $self->{config}->{assembly};
+  my $transcripts = {};
+  my $canonical_transcripts = {};
+  my $transcript_adaptor = $self->{config}->{ta};
+  my $chart_data = {};
+  my $txt_output_data = {};
+
+  my $prediction2bgcolor = {
+    'probably damaging' => 'danger',
+    'deleterious' => 'danger',
+    'possibly damaging' => 'warning',
+    'unknown'  => 'warning',
+    'benign' => 'success',
+    'tolerated' => 'success',
+  };
+
+  foreach my $individual (sort keys %$new_order) {
+    foreach my $gene_symbol (keys %{$new_order->{$individual}}) {
+      foreach my $ar (keys %{$new_order->{$individual}->{$gene_symbol}}) {
+        foreach my $transcript_stable_id (keys %{$new_order->{$individual}->{$gene_symbol}->{$ar}}) {
+          foreach my $vf_name (keys %{$new_order->{$individual}->{$gene_symbol}->{$ar}->{$transcript_stable_id}}) {
+            my $data = $individuals->{$individual}->{$gene_symbol}->{$vf_name}->{$transcript_stable_id};
+
+            my $hash = {};
+            foreach my $pair (split/;/, $data) {
+              my ($key, $value) = split('=', $pair, 2);
+              $value ||= '';
+              $hash->{$key} = $value;
+            }
+            my $vf_location = $hash->{vf_location};
+            my $existing_name = $hash->{existing_name};
+            if ($existing_name ne 'NA') {
+              $existing_name = "<a href=\"http://$assembly.ensembl.org/Homo_sapiens/Variation/Explore?v=$existing_name\">$existing_name</a>";
+            }
+            my $refseq = $hash->{refseq};
+            my $failed = $hash->{failed};
+            my $clin_sign = $hash->{clin_sig};
+            my $novel = $hash->{novel};
+            my $hgvs_t = $hash->{hgvs_t};
+            my $hgvs_p = $hash->{hgvs_p};
+            my $allelic_requirement = $hash->{allele_requirement};
+            my $observed_allelic_requirement = $hash->{ar_in_g2pdb};
+            my $consequence_types = $hash->{consequence_types};
+            my $zygosity = $hash->{zyg};
+            my $sift_score = $hash->{sift_score} || '0.0';
+            my $sift_prediction = $hash->{sift_prediction};
+            my $sift = 'NA';
+            my $sift_class = '';
+            if ($sift_prediction ne 'NA') {
+              $sift = "$sift_prediction(" . "$sift_score)";
+              $sift_class = $prediction2bgcolor->{$sift_prediction};
+            }
+            my $polyphen_score = $hash->{polyphen_score} || '0.0';
+            my $polyphen_prediction = $hash->{polyphen_prediction};
+            my $polyphen = 'NA';
+            my $polyphen_class = '';
+            if ($polyphen_prediction ne 'NA') {
+              $polyphen = "$polyphen_prediction($polyphen_score)";
+              $polyphen_class =  $prediction2bgcolor->{$polyphen_prediction};
+            }
+            
+            my %frequencies_hash = ();
+            if ($hash->{frequencies} ne 'NA') {
+              %frequencies_hash = split /[,=]/, $hash->{frequencies};
+            }
+            my @frequencies = ();
+            my @txt_output_frequencies = ();
+            foreach my $population (@frequencies_header) {
+              my $frequency = $frequencies_hash{$population} || '';
+              push @frequencies, ["$frequency"];
+              if ($frequency) {
+                push @txt_output_frequencies, "$population=$frequency";
+              }
+            }
+            my $is_canonical = 0;
+            if ($hash->{is_canonical}) {
+              $is_canonical = ($hash->{is_canonical} eq 'yes') ? 1 : 0;
+            } else {
+              if ($transcripts->{$transcript_stable_id}) {
+                $is_canonical = 1 if ($canonical_transcripts->{$transcript_stable_id});
+              } else {
+                my $transcript = $transcript_adaptor->fetch_by_stable_id($transcript_stable_id);
+                if ($transcript) {
+                  $is_canonical = $transcript->is_canonical();
+                  $transcripts->{$transcript_stable_id} = 1;
+                  $canonical_transcripts->{$transcript_stable_id} = 1 if ($is_canonical);
+                }
+              }
+            }
+            my ($location, $alleles) = split(' ', $vf_location);
+            $location =~ s/\-/:/;
+            $alleles =~ s/\//:/;
+
+            push @{$chart_data->{$individual}->{$gene_symbol}->{$ar}->{$transcript_stable_id}}, [[
+              [$vf_location], 
+              [$vf_name], 
+              [$existing_name], 
+              [$zygosity], 
+              [$observed_allelic_requirement],
+              [$consequence_types], 
+              [$clin_sign], 
+              [$sift, $sift_class], 
+              [$polyphen, $polyphen_class], 
+              [$novel], 
+              [$failed], 
+              @frequencies,
+              [$hgvs_t], 
+              [$hgvs_p], 
+              [$refseq] 
+            ], $is_canonical];
+
+            my $txt_output_variant = "$location:$alleles:$zygosity:$consequence_types:SIFT=$sift:PolyPhen=$polyphen";
+            if (@txt_output_frequencies) {
+              $txt_output_variant .= ':' . join(',', @txt_output_frequencies);
+            }
+            $txt_output_data->{$individual}->{$gene_symbol}->{$ar}->{$transcript_stable_id}->{is_canonical} = $is_canonical;
+            $txt_output_data->{$individual}->{$gene_symbol}->{$ar}->{$transcript_stable_id}->{REQ} = $observed_allelic_requirement;
+            push @{$txt_output_data->{$individual}->{$gene_symbol}->{$ar}->{$transcript_stable_id}->{variants}}, $txt_output_variant;
+          }
+        }
+      }
+    }
+  }
+  return {txt_data => $txt_output_data, chart_data => $chart_data, canonical_transcripts => $canonical_transcripts};
+}
+
+sub parse_log_files {
+  my $self = shift;
+
+  my $log_dir = $self->{user_params}->{log_dir}; 
+  my @files = <$log_dir/*>;
+
+  my $genes = {};
+  my $individuals = {};
+  my $complete_genes = {};
+  my $g2p_list = {};
+  my $in_vcf_file = {};
+  my $cache = {};
+  my $acting_ars = {};
+
+  my $new_order = {};
+
+  foreach my $file (@files) {
+    my $fh = FileHandle->new($file, 'r');
+    while (<$fh>) {
+      chomp;
+      if (/^G2P_list/) {
+        my ($flag, $gene_symbol, $DDD_category) = split/\t/;
+        $g2p_list->{$gene_symbol} = 1;
+      } elsif (/^G2P_in_vcf/) {
+        my ($flag, $gene_symbol) = split/\t/;
+        $in_vcf_file->{$gene_symbol} = 1;
+      } elsif (/^G2P_complete/) {
+        my ($flag, $gene_symbol, $tr_stable_id, $individual, $vf_name, $ars, $zyg) = split/\t/;
+        foreach my $ar (split(',', $ars)) {
+          if ($ar eq 'biallelic') {
+            # homozygous, report complete
+            if (uc($zyg) eq 'HOM') {
+              $complete_genes->{$gene_symbol}->{$individual}->{$tr_stable_id} = 1;
+              $acting_ars->{$gene_symbol}->{$individual}->{$ar} = 1;
+              $new_order->{$individual}->{$gene_symbol}->{$ar}->{$tr_stable_id}->{$vf_name} = 1;
+            }
+            # heterozygous
+            # we need to cache that we've observed one
+            elsif (uc($zyg) eq 'HET') {
+              if (scalar keys %{$cache->{$individual}->{$tr_stable_id}} >= 1) {
+                $complete_genes->{$gene_symbol}->{$individual}->{$tr_stable_id} = 1;
+                $acting_ars->{$gene_symbol}->{$individual}->{$ar} = 1;
+                $new_order->{$individual}->{$gene_symbol}->{$ar}->{$tr_stable_id}->{$vf_name} = 1;
+                # add first observed het variant to the list
+                foreach my $vf (keys %{$cache->{$individual}->{$tr_stable_id}}) {
+                  $new_order->{$individual}->{$gene_symbol}->{$ar}->{$tr_stable_id}->{$vf} = 1;
+                }
+              }
+              $cache->{$individual}->{$tr_stable_id}->{$vf_name}++;
+            }
+          }
+          # monoallelic genes require only one allele
+          elsif ($ar eq 'monoallelic' || $ar eq 'x-linked dominant' || $ar eq 'hemizygous' || $ar eq 'x-linked over-dominance') {
+            $complete_genes->{$gene_symbol}->{$individual}->{$tr_stable_id} = 1;
+            $acting_ars->{$gene_symbol}->{$individual}->{$ar} = 1;
+            $new_order->{$individual}->{$gene_symbol}->{$ar}->{$tr_stable_id}->{$vf_name} = 1;
+          }
+        }
+      } elsif (/^G2P_flag/) {
+        my ($flag, $gene_symbol, $tr_stable_id, $individual, $vf_name, $g2p_data) = split/\t/;
+        $genes->{$gene_symbol}->{"$individual\t$vf_name"}->{$tr_stable_id} = $g2p_data;
+        $individuals->{$individual}->{$gene_symbol}->{$vf_name}->{$tr_stable_id} = $g2p_data;
+      } else {
+
+      }
+    }
+    $fh->close();
+  }
+  return {
+    genes => $genes,
+    individuals => $individuals,
+    complete_genes => $complete_genes,
+    g2p_list => $g2p_list,
+    in_vcf_file => $in_vcf_file,
+    acting_ars => $acting_ars,
+    new_order => $new_order,
+  };
+}
+
+
+sub stats_html_head {
+    my $charts = shift;
+
+    my $html =<<SHTML;
+<html>
+<head>
+  <title>VEP summary</title>
+  <link rel="stylesheet" href="https://maxcdn.bootstrapcdn.com/bootstrap/3.3.7/css/bootstrap.min.css" integrity="sha384-BVYiiSIFeK1dGmJRAkycuHAHRg32OmUcww7on3RYdg4Va+PmSTsz/K68vbdEjh4u" crossorigin="anonymous">
+  <style>
+    a.inactive {
+      color: grey;
+      pointer-events:none;
+    }
+  </style>
+</head>
+<body>
+SHTML
+  return $html;
+}
+
+sub stats_html_tail {
+  my $script =<<SHTML;
+  <script src="https://ajax.googleapis.com/ajax/libs/jquery/1.12.4/jquery.min.js"></script>
+  <script src="https://maxcdn.bootstrapcdn.com/bootstrap/3.3.7/js/bootstrap.min.js"></script>
+  <script type="text/javascript" src="http://www.google.com/jsapi"></script>
+  <script>
+    \$( "input[type=checkbox]" ).on( "click", function(){
+      if (\$('.target').is(':checked')) {
+        \$( "div.not_canonical" ).hide();
+        \$("a.not_canonical").addClass("inactive");
+      } else {
+        \$( "div.not_canonical" ).show();
+        \$("a.not_canonical").removeClass("inactive");
+      }
+    } );
+  \$(document).ready(function(){
+    \$('[data-toggle="tooltip"]').tooltip(); 
+  });
+  </script>
+SHTML
+  return "\n</div>\n$script\n</body>\n</html>\n";
+}
+
+sub sort_keys {
+  my $data = shift;
+  my $sort = shift;
+  print $data, "\n";
+  my @keys;
+
+  # sort data
+  if(defined($sort)) {
+    if($sort eq 'chr') {
+      @keys = sort {($a !~ /^\d+$/ || $b !~ /^\d+/) ? $a cmp $b : $a <=> $b} keys %{$data};
+    }
+    elsif($sort eq 'value') {
+      @keys = sort {$data->{$a} <=> $data->{$b}} keys %{$data};
+    }
+    elsif(ref($sort) eq 'HASH') {
+      @keys = sort {$sort->{$a} <=> $sort->{$b}} keys %{$data};
+    }
+  }
+  else {
+    @keys = keys %{$data};
+  }
+
+  return \@keys;
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/GO.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,102 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ GO
+
+=head1 SYNOPSIS
+
+ mv GO.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin GO
+
+=head1 DESCRIPTION
+
+ A VEP plugin that retrieves Gene Ontology terms associated with
+ transcripts/translations via the Ensembl API. Requires database connection.
+ 
+=cut
+
+package GO;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+  
+  # connect to DB for offline users
+  my $config = $self->{config};
+  my $reg = $config->{reg};
+  
+  if(!defined($self->{config}->{sa})) {
+    $reg = 'Bio::EnsEMBL::Registry';
+    $reg->load_registry_from_db(
+      -host       => $config->{host},
+      -user       => $config->{user},
+      -pass       => $config->{password},
+      -port       => $config->{port},
+      -db_version => $config->{db_version},
+      -species    => $config->{species} =~ /^[a-z]+\_[a-z]+/i ? $config->{species} : undef,
+      -verbose    => $config->{verbose},
+      -no_cache   => $config->{no_slice_cache},
+    );
+  }
+  
+  return $self;
+}
+
+sub version {
+  return 73;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  return { 'GO' => 'GO terms associated with protein product'};
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  my $tr = $tva->transcript->translation;
+  return {} unless defined($tr);
+  
+  my $entries = $tr->get_all_DBEntries('GO');
+  
+  my $string = join(",", map {$_->display_id.':'.$_->description} @$entries);
+  $string =~ s/\s+/\_/g;
+  
+  return { GO => $string };
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/GXA.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,165 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+  GXA
+
+=head1 SYNOPSIS
+
+  mv GXA.pm ~/.vep/Plugins
+  ./vep -i variations.vcf --cache --plugin GXA
+
+=head1 DESCRIPTION
+
+  This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+  reports data from the Gene Expression Atlas.
+
+  NB: no account is taken for comparing values across experiments; if values
+  exist for the same tissue in more than one experiment, the highest value
+  is reported.
+
+=cut
+
+package GXA;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+
+  die("ERROR: This plugin is currently non-functional due to changes in the Gene Expression Atlas API");
+  
+  $self->{species} =  $self->{config}->{species};
+  $self->{species} =~ s/\_/\%20/;
+  
+  $self->{url} = 'https://www.ebi.ac.uk/gxa/widgets/heatmap/multiExperiment.tsv?propertyType=bioentity_identifier';
+  
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub variant_feature_types {
+  return ['BaseVariationFeature'];
+}
+
+sub get_header_info {
+  my $self = shift;
+  
+  if(!exists($self->{_header_info})) {
+    
+    # get tissues using BRCA2
+    my $url = sprintf(
+      '%s&species=%s&geneQuery=%s',
+      $self->{url},
+      $self->{species},
+      'BRCA2'
+    );
+    
+    open IN, "curl -s \"$url\" |";
+    my @lines = <IN>;
+    
+    my %headers = ();
+    
+    while(my $line = shift @lines) {
+      next if $line =~ /^#/;
+      chomp $line;
+      $line =~ s/ /\_/g;
+      %headers = map {'GXA_'.$_ => "Tissue expression level in $_ from Gene Expression Atlas"} (split /\t/, $line);
+      last;
+    }
+    
+    close IN;
+    
+    $self->{_header_info} = \%headers;
+  };
+  
+  return $self->{_header_info};
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  my $tr = $tva->transcript;
+  my $gene_id = $tr->{_gene_stable_id} || $tr->{_gene}->stable_id;
+  return {} unless $gene_id;
+  
+  if(!exists($self->{_cache}) || !exists($self->{_cache}->{$gene_id})) {
+    
+    my $url = sprintf(
+      '%s&species=%s&geneQuery=%s',
+      $self->{url},
+      $self->{species},
+      $gene_id
+    );
+    
+    open IN, "curl -s \"$url\" |";
+    
+    my $first = 1;
+    my (@headers, %data);
+    
+    while(<IN>) {
+      next if /^#/;
+      chomp;
+            
+      if($first) {
+        s/ /\_/g;
+        @headers = split /\t/, $_;
+        $first = 0;
+      }
+      else {
+        my @tmp = split /\t/, $_;
+        
+        for(my $i=0; $i<=$#headers; $i++) {
+          my ($h, $d) = ('GXA_'.$headers[$i], $tmp[$i]);
+          next unless defined($d) && $d =~ /^[0-9\.]+$/;
+          
+          if(exists($data{$h})) {
+            $data{$h} = $d if $d > $data{$h};
+          }
+          else {
+            $data{$h} = $d;
+          }
+        }
+      }
+    }
+    
+    close IN;
+    
+    $self->{_cache}->{$gene_id} = \%data;
+  }
+  
+  return $self->{_cache}->{$gene_id};
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/GeneSplicer.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,369 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ GeneSplicer
+
+=head1 SYNOPSIS
+
+ mv GeneSplicer.pm ~/.vep/Plugins
+ ./vep -i variants.vcf --plugin GeneSplicer,[path_to_genesplicer_bin],[path_to_training_dir],[option1=value],[option2=value]
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+ runs GeneSplicer (https://ccb.jhu.edu/software/genesplicer/) to get
+ splice site predictions.
+
+ It evaluates a tract of sequence either side of and including the
+ variant, both in reference and alternate states. The amount of
+ sequence included either side defaults to 100bp, but can be modified
+ by passing e.g. "context=50" as a parameter to the plugin.
+
+ Any predicted splicing regions that overlap the variant are reported
+ in the output with one of four states: no_change, diff, gain, loss
+
+ There follows a "/"-separated string consisting of the following data:
+
+ 1) type (donor, acceptor)
+ 2) coordinates (start-end)
+ 3) confidence (Low, Medium, High)
+ 4) score
+
+ Example: loss/acceptor/727006-727007/High/16.231924
+
+ If multiple sites are predicted, their reports are separated by ",".
+
+ For diff, the confidence and score for both the reference and alternate
+ sequences is reported as REF-ALT.
+
+ Example: diff/donor/621915-621914/Medium-Medium/7.020731-6.988368
+
+ Several parameters can be modified by passing them to the plugin string:
+
+ context    : change the amount of sequence added either side of
+              the variant (default: 100bp)
+ tmpdir     : change the temporary directory used (default: /tmp)
+ cache_size : change how many sequences' scores are cached in memory
+              (default: 50)
+
+ Example: --plugin GeneSplicer,$GS/bin/linux/genesplicer,$GS/human,context=200,tmpdir=/mytmp
+
+ On some systems the binaries provided will not execute, but can be compiled from source:
+
+   cd $GS/sources
+   make
+   cd -
+   ./vep [options] --plugin GeneSplicer,$GS/sources/genesplicer,$GS/human
+
+ On Mac OSX the make step is known to fail; the genesplicer.cpp file requires modification:
+
+   cd $GS/sources
+   perl -pi -e "s/^main  /int main  /" genesplicer.cpp
+   make
+ 
+
+=cut
+
+package GeneSplicer;
+
+use strict;
+use warnings;
+
+use Digest::MD5 qw(md5_hex);
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+use Bio::EnsEMBL::Variation::Utils::VariationEffect qw(overlap);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+our %DEFAULTS = (
+  context => 100,
+  tmpdir  => '/tmp',
+  cache_size => 50,
+);
+
+sub new {
+  my $class = shift;
+
+  my $self = $class->SUPER::new(@_);
+  
+  # we need sequence, so no offline mode unless we have FASTA
+  die("ERROR: cannot function in offline mode without a FASTA file\n") if $self->{config}->{offline} && !$self->{config}->{fasta};
+
+  my $params = $self->params;
+
+  my $bin = shift @$params;
+  die("ERROR: genesplicer binary not specified\n") unless $bin;
+  die("ERROR: genesplicer binary not found\n") unless -e $bin;
+  my $test = `$bin 2>&1`;
+  die("ERROR: failed to run genesplicer binary:\n$test\n") unless $test =~ /^USAGE/;
+  $self->{_bin} = $bin;
+  
+  my $training_dir = shift @$params;
+  die("ERROR: training directory not specified\n") unless $training_dir;
+  die("ERROR: training directory not found\n") unless -d $training_dir;
+  $self->{_training_dir} = $training_dir;
+
+  # defaults
+  $self->{'_param_'.$_} = $DEFAULTS{$_} for keys %DEFAULTS;
+
+  # REST API passes 1 as first param
+  shift @$params if $params->[0] && $params->[0] eq '1';
+
+  # set/override with user params
+  foreach my $param(@$params) {
+    my ($key, $val) = split('=', $param);
+    die("ERROR: Failed to parse parameter $param\n") unless defined($key) && defined($val);
+
+    $self->{'_param_'.$key} = $val;
+  }
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  return {
+    GeneSplicer => "GeneSplicer predictions"
+  };
+}
+
+sub run {
+  my ($self, $tva) = @_;
+
+  my $vf = $tva->variation_feature;
+
+  # get up and downstream sequences
+  my $up_seq = $vf->{slice}->sub_Slice(
+    $vf->{start} - $self->{'_param_context'},
+    $vf->{start} - 1,
+    $vf->strand
+  )->seq;
+
+  my $down_seq = $vf->{slice}->sub_Slice(
+    $vf->{end} + 1,
+    $vf->{end} + $self->{'_param_context'},
+    $vf->strand
+  )->seq;
+
+  # create ref seq by grabbing reference TVA
+  my $ref_seq = join("",
+    $up_seq,
+    $tva->transcript_variation->get_reference_TranscriptVariationAllele->variation_feature_seq,
+    $down_seq
+  );
+
+  return {} unless $ref_seq =~ /^[ACGT]+$/;
+
+  # create alt seq
+  my $alt_allele = $tva->variation_feature_seq;
+  $alt_allele =~ s/\-//g;
+  my $alt_seq = $up_seq.$alt_allele.$down_seq;
+
+
+  return {} unless $alt_seq =~ /^[ACGT]+$/;
+
+  # reverse comp if strands differ
+  if($tva->transcript->strand != $vf->strand) {
+    reverse_comp(\$ref_seq);
+    reverse_comp(\$alt_seq);
+  }
+
+  # get results
+  my $ref_results = $self->results_from_cache($ref_seq) || $self->results_from_seq($ref_seq);
+  my $alt_results = $self->results_from_cache($alt_seq) || $self->results_from_seq($alt_seq);
+
+  # compare results both ways
+  my $diff_ref_to_alt = $self->compare_results($ref_results, $alt_results);
+  my $diff_alt_to_ref = $self->compare_results($alt_results, $ref_results);
+
+  # get VF pos relative to tested sequence
+  my ($vf_start, $vf_end) = ($self->{'_param_context'} + 1, $self->{'_param_context'} + (($vf->{end} - $vf->{start}) + 1));
+
+  # get overlapping losses and gains
+  # and map to chromosome coords
+  my @losses =
+    map {$_->{gl} = 'loss'; $_}
+    @{$diff_ref_to_alt->{lost}};
+
+  my @gains = 
+    map {$_->{gl} = 'gain'; $_}
+    @{$diff_alt_to_ref->{lost}};
+
+  my @diffs = 
+    map {$_->{gl} = 'diff'; $_}
+    @{$diff_ref_to_alt->{diff}};
+
+  my $return = join(',',
+    map {
+      join('/',
+        $_->[0]->{gl},
+        $_->[0]->{type},
+        $_->[1]->{end5}.'-'.$_->[1]->{end3},
+        $_->[0]->{confidence},
+        $_->[0]->{score}
+      )
+    }
+    map {[$_, $self->map_ss_coords($_, $vf)]}
+    grep {overlap($vf_start, $vf_end, $_->{end5}, $_->{end3})}
+    (@losses, @gains, @diffs)
+  );
+
+  # probably of interest to report splice sites were found
+  # but no difference between ref and alt
+  if(!$return && grep {overlap($vf_start, $vf_end, $_->{end5}, $_->{end3})} @$ref_results) {
+    $return = join(',',
+      map {
+        join('/',
+          'no_change',
+          $_->[0]->{type},
+          $_->[1]->{end5}.'-'.$_->[1]->{end3},
+          $_->[0]->{confidence},
+          $_->[0]->{score}
+        )
+      }
+      map {[$_, $self->map_ss_coords($_, $vf)]}
+      grep {overlap($vf_start, $vf_end, $_->{end5}, $_->{end3})} @$ref_results
+    );
+  }
+
+  return $return ? { GeneSplicer => $return } : {};
+}
+
+sub results_from_seq {
+  my $self = shift;
+  my $seq = shift;
+
+  # write seqs to file
+  my $seq_file = $self->{'_param_tmpdir'}."/genesplicer_$$.fa";
+  open SEQ, ">$seq_file" or die("ERROR: Could not write to temporary sequence file $seq_file\n");
+  print SEQ ">SEQ\n$seq\n";
+  close SEQ;
+
+  my $result_file = $self->{'_param_tmpdir'}."/genesplicer_$$.results";
+  
+  my $cmd = sprintf(
+    '%s %s %s -f %s',
+    $self->{'_bin'},
+    $seq_file,
+    $self->{'_training_dir'},
+    $result_file
+  );
+
+  my $output = `$cmd 2>&1`;
+  unlink($seq_file);
+
+  return [] unless -e $result_file;
+
+  open RES, $result_file;
+  my @results;
+  
+  while(<RES>) {
+    chomp;
+    my ($end5, $end3, $score, $confidence, $type) = split;
+
+    push @results, {
+      end5 => $end5,
+      end3 => $end3,
+      score => $score,
+      confidence => $confidence,
+      type => $type
+    };
+  }
+  close RES;
+
+  unlink($result_file);
+
+  push @{$self->{cache}}, { hex => md5_hex($seq), results => \@results};
+  shift @{$self->{cache}} while scalar @{$self->{cache}} > $self->{_param_cache_size};
+
+  return \@results;
+}
+
+sub results_from_cache {
+  my $self = shift;
+  my $seq = shift;
+
+  my ($results) = map {$_->{results}} grep {$_->{hex} eq md5_hex($seq)} @{$self->{cache} || []};
+
+  return $results;
+}
+
+sub compare_results {
+  my $self = shift;
+  my $a = shift;
+  my $b = shift;
+
+  my (@diff, @lost);
+
+  foreach my $res_a(@$a) {
+    my @match = grep {
+      $_->{end5} == $res_a->{end5} &&
+      $_->{end3} == $res_a->{end3} &&
+      $_->{type} eq $res_a->{type}
+    } @$b;
+
+    # result not found in b
+    if(!@match) {
+      push @lost, $res_a;
+    }
+
+    # >1 result found
+    elsif(scalar @match > 1) {
+      warn("WARNING: Found two matches?\n");
+    }
+
+    # 1 match
+    elsif($match[0]->{score} != $res_a->{score}) {
+      my %diff = %$res_a;
+      $diff{score}      .= '-'.$match[0]->{score};
+      $diff{confidence} .= '-'.$match[0]->{confidence};
+      push @diff, \%diff;
+    }
+  }
+
+  return { diff => \@diff, lost => \@lost};
+}
+
+sub map_ss_coords {
+  my $self = shift;
+  my $res = shift;
+  my $vf = shift;
+
+  my $return = {};
+
+  foreach my $coord(qw(end5 end3)) {
+    $return->{$coord} = (($res->{$coord} - $self->{'_param_context'}) + $vf->{start}) - 1;
+  }
+
+  return $return;
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/HGVSReferenceBase.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,78 @@
+=head1 LICENSE
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+     http://www.apache.org/licenses/LICENSE-2.0
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+  HGVSReferenceBase
+
+=head1 SYNOPSIS
+
+  mv HGVSReferenceBase.pm ~/.vep/Plugins
+  ./vep -i variations.vcf --cache --hgvs --plugin HGVSReferenceBase
+
+=head1 DESCRIPTION
+
+  This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+  reports the reference base for the variant, as used in the longer form.
+  of HGVS. To be used with --hgvs option.
+
+=cut
+
+
+package HGVSReferenceBase;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+use Bio::EnsEMBL::Variation::DBSQL::TranscriptVariationAdaptor;
+use Bio::EnsEMBL::Variation::DBSQL::DBAdaptor;
+use Bio::EnsEMBL::Variation::TranscriptVariationAllele;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub variant_feature_types {
+  return ['VariationFeature'];
+}
+
+sub get_header_info {
+  my $self = shift;
+  
+  return {
+    'HGVS_ref' => 'Reference base as may be reported in HGVS transcript level notation',
+  };
+}
+
+sub run {
+  my ($self, $tva) = @_;
+
+  # check var class, this is only useful for  deletions 
+  # or duplications -  a subset of insertions
+  return {} unless $tva->variation_feature->var_class() =~ /del|ins/;
+
+  return $tva->hgvs_transcript_reference() ? {'HGVS_ref' => $tva->hgvs_transcript_reference()} : {};
+
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/LD.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,277 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+   http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+  
+=cut
+
+=head1 NAME
+
+ LD
+
+=head1 SYNOPSIS
+
+ mv LD.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin LD,1000GENOMES:phase_3:CEU,0.8
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+ finds variants in linkage disequilibrium with any overlapping existing 
+ variants from the Ensembl variation databases. You can configure the 
+ population used to calculate the r2 value, and the r2 cutoff used by 
+ passing arguments to the plugin via the VEP command line (separated 
+ by commas). This plugin adds a single new entry to the Extra column 
+ with a comma-separated list of linked variant IDs and the associated 
+ r2 values, e.g.:
+
+   LinkedVariants=rs123:0.879,rs234:0.943
+
+ If no arguments are supplied, the default population used is the CEU
+ sample from the 1000 Genomes Project phase 3, and the default r2
+ cutoff used is 0.8.
+
+ WARNING: Calculating LD is a relatively slow procedure, so this will 
+ slow VEP down considerably when running on large numbers of
+ variants. Consider running vep followed by filter_vep to get a smaller
+ input set:
+
+   ./vep -i input.vcf -cache -vcf -o input_vep.vcf
+   ./filter_vep -i input_vep.vcf -filter "Consequence is missense_variant" > input_vep_filtered.vcf
+   ./vep -i input_vep_filtered.vcf -cache -plugin LD
+
+=cut
+
+=head1 INSTALLATION
+
+ LD calculation requires additional installation steps.
+
+ The JSON perl library is required; see VEP's installation instructions
+ for guidance: http://www.ensembl.org/info/docs/tools/vep/script/vep_download.html#additional
+
+ A binary from the ensembl-variation git repository must be compiled and either
+ added to your PATH or specified on the command line. In the ensembl-vep
+ directory:
+
+   export HTSLIB_DIR=${PWD}/htslib
+   git clone https://github.com/Ensembl/ensembl-variation
+   cd ensembl-variation/C_code
+   make
+
+ You may EITHER add this path to your PATH environment variable (add this line
+ to your $HOME/.bashrc to make the change permanent):
+
+   export PATH=${PATH}:${PWD}
+
+ OR you may specify the full path to the ld_vcf binary on the vep command line:
+
+   ./vep -i variations.vcf --plugin LD,1000GENOMES:phase_3:CEU,0.8,$PWD/ensembl-variation/C_code/ld_vcf
+
+=cut
+
+=head1 DATA
+
+ By default genotype data to calculate LD is retrieved from tabix-indexed
+ VCF files hosted on Ensembl's FTP servers. It is possible to download this
+ data to your local machine and have the LD plugin read genotype data from
+ there instead, giving faster performance and reducing network traffic.
+
+ These commands show how to get the data files for GRCh38.
+
+   mkdir variation_genotype
+   cd variation_genotype
+   lftp -e "mget ALL.chr*.phase3_shapeit2_mvncall_integrated_v3plus_nounphased.rsID.genotypes.GRCh38_dbSNP.vcf.gz*" ftp://ftp.ensembl.org/pub/data_files/homo_sapiens/GRCh38/variation_genotype/
+   cd ..
+
+ For GRCh37 replace the lftp command with:
+
+   lftp -e "mget ALL.chr*.phase3_shapeit2_mvncall_integrated_v3plus_nounphased.rsID.genotypes.vcf.gz*" ftp://ftp.ensembl.org/pub/data_files/homo_sapiens/GRCh37/variation_genotype/
+
+ We must now modify the JSON configuration file used to find the data. Starting
+ in the ensembl-vep directory:
+
+   perl -pi -e "s|ftp://ftp.ensembl.org/pub/data_files/homo_sapiens/GRCh38|$PWD|" Bio/EnsEMBL/Variation/DBSQL/vcf_config.json
+
+ Or for GRCh37:
+
+   perl -pi -e "s|ftp://ftp.ensembl.org/pub/data_files/homo_sapiens/GRCh37|$PWD|" Bio/EnsEMBL/Variation/DBSQL/vcf_config.json 
+
+=cut
+
+package LD;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Registry;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub feature_types {
+  return ['Feature','Intergenic'];
+}
+
+sub get_header_info {
+
+  my $self = shift;
+  
+  return {
+    LinkedVariants => "Variants in LD (r2 >= ".$self->{r2_cutoff}.
+      ") with overlapping existing variants from the ".
+      $self->{pop}->name." population",
+  };
+}
+
+sub new {
+  my $class = shift;
+
+  my $self = $class->SUPER::new(@_);
+
+  if ($self->config->{offline}) {
+    warn "Warning: a connection to the database is required to calculate LD\n";
+  }
+
+  my $reg = 'Bio::EnsEMBL::Registry';
+
+  # turn on the check for existing variants
+
+  $self->config->{check_existing} = 1;
+
+  # fetch our population
+
+  my ($pop_name, $r2_cutoff, $ld_binary) = @{ $self->params };
+
+  # set some defaults
+
+  $pop_name ||= '1000GENOMES:phase_3:CEU';
+
+  $r2_cutoff = 0.8 unless defined $r2_cutoff;
+
+  my $pop_adap = $reg->get_adaptor('human', 'variation', 'population')
+    || die "Failed to get population adaptor\n";
+
+  my $valid_pops = $pop_adap->fetch_all_LD_Populations();
+  my ($pop) = grep {$_->name eq $pop_name} @$valid_pops;
+  die "Invalid population '$pop_name'; valid populations are:\n".join(", ", map {$_->name} @$valid_pops)."\n" unless $pop;
+
+  $self->{pop} = $pop;
+  $self->{r2_cutoff} = $r2_cutoff;
+  
+  # prefetch the necessary adaptors
+  
+  my $ld_adap = $reg->get_adaptor('human', 'variation', 'ldfeaturecontainer')
+    || die "Failed to get LD adaptor\n";
+  $ld_adap->db->use_vcf(1);
+  my $var_adap = $reg->get_adaptor('human', 'variation', 'variation')
+    || die "Failed to get variation adaptor\n";
+    
+  my $var_feat_adap = $reg->get_adaptor('human', 'variation', 'variationfeature')
+    || die "Failed to get variation feature adaptor\n";
+
+  if($ld_binary) {
+    die("Specified LD binary \"$ld_binary\" does not exist\n") unless -e $ld_binary;
+    $Bio::EnsEMBL::Variation::DBSQL::LDFeatureContainerAdaptor::VCF_BINARY_FILE = $ld_binary;
+  }
+   
+  $self->{ld_adap} = $ld_adap;
+  $self->{var_adap} = $var_adap;
+  $self->{var_feat_adap} = $var_feat_adap;
+
+  return $self;
+}
+
+sub run {
+  my ($self, $vfoa, $line_hash) = @_;
+
+  # fetch the existing variants from the line hash
+  return {} unless $line_hash->{Existing_variation};
+
+  my @vars = ref($line_hash->{Existing_variation}) eq 'ARRAY' ? @{$line_hash->{Existing_variation}} : split(',', $line_hash->{Existing_variation});
+
+  my @linked;
+
+
+  for my $var (@vars) {
+
+    # check cache
+    my $res;
+
+    if($self->{cache}) {
+      ($res) = grep {$_->{var} eq $var} @{$self->{cache}};
+    }
+    
+    unless($res) {
+      my @this_linked;
+    
+      # fetch a variation for each overlapping variant ID
+      if (my $v = $self->{var_adap}->fetch_by_name($var)) {
+
+        # and fetch the associated variation features
+
+        for my $vf (@{ $self->{var_feat_adap}->fetch_all_by_Variation($v) }) {
+
+          # we're only interested in variation features that overlap our variant
+
+          if ($vf->slice->name eq $vfoa->variation_feature->slice->name) {
+
+            # fetch an LD feature container for this variation feature and our preconfigured population
+            if (my $ldfc = $self->{ld_adap}->fetch_by_VariationFeature($vf, $self->{pop})) {
+            
+              # loop over all the linked variants
+              # we pass 1 to get_all_ld_values() so that it doesn't lazy load
+              # VariationFeature objects - we only need the name here anyway
+              for my $result (@{ $ldfc->get_all_ld_values(1) }) {
+              
+                # apply our r2 cutoff
+
+                if ($result->{r2} >= $self->{r2_cutoff}) {
+
+                  my $v1 = $result->{variation_name1};
+                  my $v2 = $result->{variation_name2};
+
+                  # I'm not sure which of these are the query variant, so just check the names
+                    
+                  my $linked = $v1 eq $var ? $v2 : $v1;
+                  
+                  push @this_linked, sprintf("%s:%.3f", $linked, $result->{r2});
+                }
+              }
+            }
+          }
+        }
+      }
+
+      # cache it
+      $res = {
+        var => $var,
+        linked => \@this_linked
+      };
+
+      push @{$self->{cache}}, $res;
+      shift @{$self->{cache}} while scalar @{$self->{cache}} > 50;
+    }
+
+    push @linked, @{$res->{linked}};
+  }
+
+  return scalar @linked ? {LinkedVariants => join(',', @linked)} : {};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/LICENSE	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,202 @@
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+                           Version 2.0, January 2004
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+
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+
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+   Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+   Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+   Licensed under the Apache License, Version 2.0 (the "License");
+   you may not use this file except in compliance with the License.
+   You may obtain a copy of the License at
+
+       http://www.apache.org/licenses/LICENSE-2.0
+
+   Unless required by applicable law or agreed to in writing, software
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\ No newline at end of file

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/LOVD.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,128 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ LOVD
+
+=head1 SYNOPSIS
+
+ mv LOVD.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin LOVD
+
+=head1 DESCRIPTION
+
+ A VEP plugin that retrieves LOVD variation data from http://www.lovd.nl/.
+ 
+ Please be aware that LOVD is a public resource of curated variants, therefore
+ please respect this resource and avoid intensive querying of their databases
+ using this plugin, as it will impact the availability of this resource for
+ others.
+
+=cut
+
+package LOVD;
+
+use strict;
+use warnings;
+use LWP::UserAgent;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub version {
+    return '2.5';
+}
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub get_header_info {
+    return {
+        LOVD => "LOVD variant ID",
+    };
+}
+
+sub run {
+    my ($self, $tva) = @_;
+    
+    $self->{has_cache} = 1;
+
+    my %hg_assembly = ( 'grch37' => 'hg19', 'grch38' => 'hg38' );
+    my $assembly = lc($self->{config}->{assembly});
+
+    # only works on human
+    die("ERROR: LOVD plugin works only on human data") unless $self->{config}->{species} =~ /human|homo/i;
+    
+    # only work on 2 human assemblies
+    die("ERROR: LOVD plugin works only on human assemblies ".join(' and ', keys(%hg_assembly))) unless $hg_assembly{$assembly};
+
+    # get the VF object
+    my $vf = $tva->variation_feature;
+    return {} unless defined $vf;
+    
+    # set up a LWP UserAgent
+    my $ua = LWP::UserAgent->new;
+    $ua->env_proxy;
+
+    my $chr = $vf->{chr};
+    $chr =~ s/^chr//;
+    
+    my $locus = sprintf('chr%s:%s_%s', $chr, $vf->{start}, $vf->{end});
+    
+    my $data;
+    
+    # check the cache
+    if(!exists($self->{lovd_cache}->{$locus})) {
+        
+        # construct a LOVD URL
+        my $url = sprintf('http://www.lovd.nl/search.php?build=%s&position=%s', $hg_assembly{$assembly}, $locus);
+        
+        # get the accession (only need the head to get the redirect URL that contains the accession)
+        my $response = $ua->get($url);
+        
+        if($response->is_success) {
+            
+            # parse the data into a hash
+            for(grep {$_ !~ /hg_build/} split /\cJ/, $response->decoded_content) {
+                s/\"//g;
+                
+                my ($build, $pos, $gene, $acc, $dna, $url) = split /\t/;
+                
+                $data = join(',', $gene, $acc, $dna)
+            }
+            
+            $self->{lovd_cache}->{$locus} = $data;
+        }
+    }
+    else {
+        $data = $self->{lovd_cache}->{$locus};
+    }
+    
+    return $data ? { LOVD => $data } : {};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/LoFtool.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,122 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ LoFtool
+
+=head1 SYNOPSIS
+
+  mv LoFtool.pm ~/.vep/Plugins
+  mv LoFtool_scores.txt ~/.vep/Plugins
+  ./vep -i variants.vcf --plugin LoFtool
+
+=head1 DESCRIPTION
+
+  Add LoFtool scores to the VEP output.
+
+  LoFtool provides a rank of genic intolerance and consequent
+  susceptibility to disease based on the ratio of Loss-of-function (LoF)
+  to synonymous mutations for each gene in 60,706 individuals from ExAC,
+  adjusting for the gene de novo mutation rate and evolutionary protein
+  conservation. The lower the LoFtool gene score percentile the most
+  intolerant is the gene to functional variation. For more details please see
+  (Fadista J et al. 2017), PMID:27563026.
+  The authors would like to thank the Exome Aggregation Consortium and
+  the groups that provided exome variant data for comparison. A full
+  list of contributing groups can be found at http://exac.broadinstitute.org/about.
+
+  The LoFtool_scores.txt file is found alongside the plugin in the
+  VEP_plugins GitHub repo.
+
+  To use another scores file, add it as a parameter i.e.
+
+  ./vep -i variants.vcf --plugin LoFtool,scores_file.txt
+
+=cut
+
+package LoFtool;
+
+use strict;
+use warnings;
+
+use DBI;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub new {
+  my $class = shift;
+
+  my $self = $class->SUPER::new(@_);
+  
+  my $file = $self->params->[0];
+
+  if(!$file) {
+    my $plugin_dir = $INC{'LoFtool.pm'};
+    $plugin_dir =~ s/LoFtool\.pm//i;
+    $file = $plugin_dir.'/LoFtool_scores.txt';
+  }
+  
+  die("ERROR: LoFtool scores file $file not found\n") unless $file && -e $file;
+  
+  open IN, $file;
+  my %scores;
+  
+  while(<IN>) {
+    chomp;
+    my ($gene, $score) = split;
+    next if !defined($score) || $score eq 'LoFtool_percentile';
+    $scores{lc($gene)} = sprintf("%g", $score);
+  }
+  
+  close IN;
+  
+  die("ERROR: No scores read from $file\n") unless scalar keys %scores;
+  
+  $self->{scores} = \%scores;
+  
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  return {
+    LoFtool => "LoFtool score for gene"
+  };
+}
+
+sub run {
+  my $self = shift;
+  my $tva = shift;
+  
+  my $symbol = $tva->transcript->{_gene_symbol} || $tva->transcript->{_gene_hgnc};
+  return {} unless $symbol;
+  
+  return $self->{scores}->{lc($symbol)} ? { LoFtool => $self->{scores}->{lc($symbol)}} : {};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/LoFtool_scores.txt	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,14516 @@
+Gene	LoFtool_percentile
+NIPBL	6.89E-05
+SCN1A	1.38E-04
+NOTCH1	2.07E-04
+TSC2	2.76E-04
+PTCH1	3.44E-04
+SCN5A	4.13E-04
+EP300	4.82E-04
+CACNA1C	5.51E-04
+CACNA1G	6.20E-04
+SMARCA4	6.89E-04
+ATP2B3	7.58E-04
+KCNH2	8.27E-04
+FLNA	8.96E-04
+TP53	9.65E-04
+LMNA	1.03E-03
+CREBBP	1.10E-03
+RREB1	1.17E-03
+GRM7	1.24E-03
+CACNA1E	1.31E-03
+NAV1	1.38E-03
+SCN2A	1.45E-03
+DAG1	1.52E-03
+F8	1.58E-03
+MLH1	1.65E-03
+MGAT1	1.72E-03
+FGFR2	1.79E-03
+NSD1	1.86E-03
+RALGAPB	1.93E-03
+CASZ1	2.00E-03
+BRCA1	2.07E-03
+PSEN1	2.14E-03
+DYSF	2.20E-03
+KIT	2.27E-03
+NRXN3	2.34E-03
+KCNH4	2.41E-03
+RYR1	2.48E-03
+COL4A5	2.55E-03
+LRP1	2.62E-03
+FLNB	2.69E-03
+WHSC1	2.76E-03
+KCNQ2	2.82E-03
+FBN1	2.89E-03
+ATP1A3	2.96E-03
+HCFC1	3.03E-03
+ACTB	3.10E-03
+ESR1	3.17E-03
+RET	3.24E-03
+ABL1	3.31E-03
+SOX30	3.38E-03
+KCNQ1	3.44E-03
+NLRP3	3.51E-03
+DLL1	3.58E-03
+MECP2	3.65E-03
+COL6A3	3.72E-03
+FOXK1	3.79E-03
+APC	3.86E-03
+NUP98	3.93E-03
+ATP2B2	4.00E-03
+COL1A1	4.06E-03
+TBX3	4.13E-03
+CACNA1D	4.20E-03
+APP	4.27E-03
+LRP2	4.34E-03
+GRIK3	4.41E-03
+TRIM71	4.48E-03
+CAMTA1	4.55E-03
+SERPINA1	4.62E-03
+HELZ	4.68E-03
+CTNND2	4.75E-03
+DAB2IP	4.82E-03
+COL5A2	4.89E-03
+ZNF521	4.96E-03
+FUS	5.03E-03
+CACNA1H	5.10E-03
+ATRX	5.17E-03
+FGFR1	5.24E-03
+CASR	5.30E-03
+UBTF	5.37E-03
+TSC1	5.44E-03
+ATP2B1	5.51E-03
+ARSA	5.58E-03
+SERPING1	5.65E-03
+SCN4A	5.72E-03
+SRCAP	5.79E-03
+SCN3A	5.86E-03
+PCIF1	5.92E-03
+ZNF608	5.99E-03
+MYH9	6.06E-03
+MYH11	6.13E-03
+CHAT	6.20E-03
+JAG1	6.27E-03
+LIN54	6.34E-03
+COL2A1	6.41E-03
+DHX30	6.48E-03
+SETD1A	6.54E-03
+FLNC	6.61E-03
+TP63	6.68E-03
+ATP2A3	6.75E-03
+WFS1	6.82E-03
+ADNP	6.89E-03
+RLF	6.96E-03
+NUFIP2	7.03E-03
+COL1A2	7.10E-03
+MSL2	7.17E-03
+GCK	7.23E-03
+ATP1A1	7.30E-03
+ASH1L	7.37E-03
+OCRL	7.44E-03
+ZNF609	7.51E-03
+PAX7	7.58E-03
+EXT1	7.65E-03
+PKHD1	7.72E-03
+MGAT5	7.79E-03
+FBN2	7.85E-03
+SYK	7.92E-03
+RBM14	7.99E-03
+RB1	8.06E-03
+VCAN	8.13E-03
+ELFN2	8.20E-03
+GBA	8.27E-03
+GNAS	8.34E-03
+NF2	8.41E-03
+MGA	8.47E-03
+OPA1	8.54E-03
+SLC12A5	8.61E-03
+EEF1D	8.68E-03
+THRB	8.75E-03
+PC	8.82E-03
+EP400	8.89E-03
+SUPT5H	8.96E-03
+ATP2C1	9.03E-03
+SOX6	9.09E-03
+LRP1B	9.16E-03
+PAX3	9.23E-03
+ZNF592	9.30E-03
+KCNB1	9.37E-03
+COL11A1	9.44E-03
+HBB	9.51E-03
+JAG2	9.58E-03
+EIF4ENIF1	9.65E-03
+MSH2	9.71E-03
+GRM5	9.78E-03
+ABCA2	9.85E-03
+DNMT3B	9.92E-03
+PLEC	9.99E-03
+ERCC6L	1.01E-02
+PDZD8	1.01E-02
+KCNC1	1.02E-02
+PPARD	1.03E-02
+BEST1	1.03E-02
+MTA1	1.04E-02
+DPYSL5	1.05E-02
+CYBB	1.05E-02
+SMARCC2	1.06E-02
+ABCA4	1.07E-02
+NR1I3	1.07E-02
+DACH2	1.08E-02
+GLG1	1.09E-02
+EMR2	1.10E-02
+AHDC1	1.10E-02
+MLLT1	1.11E-02
+PPFIA3	1.12E-02
+PML	1.12E-02
+LRP8	1.13E-02
+COL5A1	1.14E-02
+CLCN2	1.14E-02
+LTBP1	1.15E-02
+MBD5	1.16E-02
+SNPH	1.16E-02
+TRPV4	1.17E-02
+GABRD	1.18E-02
+C11orf30	1.18E-02
+TMEM201	1.19E-02
+EYA1	1.20E-02
+SCN9A	1.21E-02
+KCNQ5	1.21E-02
+MTMR3	1.22E-02
+COL4A1	1.23E-02
+TNS1	1.23E-02
+ELANE	1.24E-02
+AR	1.25E-02
+NR5A1	1.25E-02
+COL6A2	1.26E-02
+ZNF777	1.27E-02
+LCOR	1.27E-02
+CACNB2	1.28E-02
+SYNPO	1.29E-02
+TENC1	1.30E-02
+SMARCAD1	1.30E-02
+ANKRD11	1.31E-02
+PAH	1.32E-02
+CACNA1I	1.32E-02
+ZNF827	1.33E-02
+PRKAG2	1.34E-02
+CLCN5	1.34E-02
+EZH2	1.35E-02
+HNF4A	1.36E-02
+MED13	1.36E-02
+CHD3	1.37E-02
+CDKN2AIP	1.38E-02
+RORC	1.38E-02
+DPYSL2	1.39E-02
+INTS6	1.40E-02
+FBN3	1.41E-02
+ITPR1	1.41E-02
+EFEMP1	1.42E-02
+RXRA	1.43E-02
+PRNP	1.43E-02
+CHD5	1.44E-02
+CRMP1	1.45E-02
+ACVR2B	1.45E-02
+GLI3	1.46E-02
+POLG	1.47E-02
+SAP130	1.47E-02
+CPS1	1.48E-02
+CSDE1	1.49E-02
+HIC2	1.50E-02
+NPC1L1	1.50E-02
+ABCA12	1.51E-02
+ABCC11	1.52E-02
+ZMYND8	1.52E-02
+SETDB1	1.53E-02
+LRP5	1.54E-02
+FOXM1	1.54E-02
+TBX18	1.55E-02
+RARB	1.56E-02
+NOTCH2	1.56E-02
+SCN8A	1.57E-02
+HIRA	1.58E-02
+FXN	1.58E-02
+CYB5R3	1.59E-02
+HIVEP2	1.60E-02
+WHSC1L1	1.61E-02
+CIC	1.61E-02
+LEF1	1.62E-02
+MBD1	1.63E-02
+MME	1.63E-02
+TFAP2A	1.64E-02
+SACS	1.65E-02
+CAND1	1.65E-02
+SLC8A2	1.66E-02
+INO80	1.67E-02
+SULF2	1.67E-02
+KCNE1	1.68E-02
+TAF3	1.69E-02
+G6PD	1.69E-02
+SULF1	1.70E-02
+RORA	1.71E-02
+POMT1	1.72E-02
+ABCB4	1.72E-02
+GRM1	1.73E-02
+CPT1B	1.74E-02
+SETD5	1.74E-02
+CSF2RA	1.75E-02
+COL27A1	1.76E-02
+RAP1GAP	1.76E-02
+HIPK1	1.77E-02
+XKR4	1.78E-02
+MFN2	1.78E-02
+TP73	1.79E-02
+NR4A2	1.80E-02
+SBNO1	1.81E-02
+L1CAM	1.81E-02
+THOC2	1.82E-02
+EHMT1	1.83E-02
+FOXA2	1.83E-02
+EIF3A	1.84E-02
+WBP11	1.85E-02
+GABRA1	1.85E-02
+NNT	1.86E-02
+ZEB2	1.87E-02
+CDC42BPB	1.87E-02
+ABCD1	1.88E-02
+MED1	1.89E-02
+KCNJ11	1.89E-02
+TH	1.90E-02
+NEFM	1.91E-02
+DYNC1H1	1.92E-02
+ADARB1	1.92E-02
+FRMPD4	1.93E-02
+ABCC6	1.94E-02
+BCL11A	1.94E-02
+ITGB1	1.95E-02
+HEPH	1.96E-02
+NELL2	1.96E-02
+ATP7A	1.97E-02
+CAPN3	1.98E-02
+SLC4A4	1.98E-02
+GNAI2	1.99E-02
+ERF	2.00E-02
+NTRK2	2.00E-02
+TRAPPC9	2.01E-02
+ACTL6A	2.02E-02
+FBLN1	2.03E-02
+AMPD3	2.03E-02
+SAFB	2.04E-02
+GFAP	2.05E-02
+APLP2	2.05E-02
+COL11A2	2.06E-02
+SLC7A2	2.07E-02
+COL3A1	2.07E-02
+GNA11	2.08E-02
+SERBP1	2.09E-02
+PRKCE	2.09E-02
+NPHP4	2.10E-02
+DCTN1	2.11E-02
+BRAF	2.12E-02
+MSH6	2.12E-02
+YAP1	2.13E-02
+QRICH1	2.14E-02
+LRRC4	2.14E-02
+ARID1A	2.15E-02
+SUPT6H	2.16E-02
+ECE1	2.16E-02
+SRC	2.17E-02
+UPF1	2.18E-02
+EFTUD2	2.18E-02
+SMC1A	2.19E-02
+SOBP	2.20E-02
+ATP2A2	2.20E-02
+EIF2B5	2.21E-02
+TRIM46	2.22E-02
+TRPS1	2.23E-02
+TRPC5	2.23E-02
+LBR	2.24E-02
+SF1	2.25E-02
+FGFR3	2.25E-02
+KCNJ2	2.26E-02
+FLT4	2.27E-02
+ABCB1	2.27E-02
+SLC12A3	2.28E-02
+KIAA0430	2.29E-02
+EPB41L2	2.29E-02
+FURIN	2.30E-02
+MAP2K7	2.31E-02
+TFAP2D	2.31E-02
+PSEN2	2.32E-02
+BTAF1	2.33E-02
+CHD1	2.34E-02
+MYOCD	2.34E-02
+CFTR	2.35E-02
+UBAP2L	2.36E-02
+NCAPH2	2.36E-02
+ITGB8	2.37E-02
+MYCN	2.38E-02
+TNFRSF25	2.38E-02
+GNAZ	2.39E-02
+GABRA4	2.40E-02
+ACTN4	2.40E-02
+SLC26A1	2.41E-02
+LRRC4C	2.42E-02
+NFIL3	2.43E-02
+MUTYH	2.43E-02
+KRT6A	2.44E-02
+SETX	2.45E-02
+THRA	2.45E-02
+KCNMA1	2.46E-02
+NRP2	2.47E-02
+MOV10L1	2.47E-02
+MAML1	2.48E-02
+QKI	2.49E-02
+SOS1	2.49E-02
+C10orf2	2.50E-02
+HMBS	2.51E-02
+SYNJ1	2.51E-02
+GATA3	2.52E-02
+SMAD1	2.53E-02
+SLC12A6	2.54E-02
+ZNF652	2.54E-02
+CLTA	2.55E-02
+CPSF7	2.56E-02
+GNAL	2.56E-02
+KCNC2	2.57E-02
+KIF11	2.58E-02
+SKIL	2.58E-02
+BNC1	2.59E-02
+MYO7A	2.60E-02
+ZC3H10	2.60E-02
+XPO4	2.61E-02
+FOXP3	2.62E-02
+ANKRD17	2.62E-02
+NR0B1	2.63E-02
+GRAMD4	2.64E-02
+EXOC7	2.65E-02
+DCX	2.65E-02
+LYN	2.66E-02
+SNRK	2.67E-02
+NFRKB	2.67E-02
+TCF7L2	2.68E-02
+NMNAT2	2.69E-02
+WDR20	2.69E-02
+PAX8	2.70E-02
+HNRNPUL1	2.71E-02
+IRF2BP1	2.71E-02
+KCNA2	2.72E-02
+RANBP3	2.73E-02
+ABCA3	2.74E-02
+PARP8	2.74E-02
+ZNF445	2.75E-02
+DEDD	2.76E-02
+SMOX	2.76E-02
+PAX5	2.77E-02
+XKR7	2.78E-02
+GCH1	2.78E-02
+FASN	2.79E-02
+GDNF	2.80E-02
+TRIM33	2.80E-02
+CPEB1	2.81E-02
+SLC12A4	2.82E-02
+COL4A6	2.82E-02
+CHD7	2.83E-02
+KCNH6	2.84E-02
+JMJD1C	2.85E-02
+RAB11FIP4	2.85E-02
+TKTL1	2.86E-02
+ZBED4	2.87E-02
+ZC3H14	2.87E-02
+KCND3	2.88E-02
+ATP13A2	2.89E-02
+SLC26A9	2.89E-02
+MTSS1	2.90E-02
+GRM8	2.91E-02
+PTCH2	2.91E-02
+MYH14	2.92E-02
+SOCS6	2.93E-02
+LHX6	2.93E-02
+SETD2	2.94E-02
+DLL4	2.95E-02
+FKBP8	2.96E-02
+MOV10	2.96E-02
+SETBP1	2.97E-02
+DHRS3	2.98E-02
+NR3C2	2.98E-02
+ABCB9	2.99E-02
+RALGAPA1	3.00E-02
+CACNA1S	3.00E-02
+EPB41L4B	3.01E-02
+ONECUT1	3.02E-02
+CTBP2	3.02E-02
+ADCY9	3.03E-02
+NACC1	3.04E-02
+CBS	3.05E-02
+IPO7	3.05E-02
+VWF	3.06E-02
+FBXL16	3.07E-02
+FOXA3	3.07E-02
+ABCF2	3.08E-02
+PSMD2	3.09E-02
+DGCR8	3.09E-02
+GANAB	3.10E-02
+PRPF3	3.11E-02
+VDR	3.11E-02
+ATP2B4	3.12E-02
+SERPINF2	3.13E-02
+EIF2B4	3.13E-02
+ABCB5	3.14E-02
+GAA	3.15E-02
+SLC26A11	3.16E-02
+ENG	3.16E-02
+LRP4	3.17E-02
+ZIC1	3.18E-02
+PHKA1	3.18E-02
+CHST1	3.19E-02
+ZMYM3	3.20E-02
+DHCR24	3.20E-02
+ACTG1	3.21E-02
+KCNH3	3.22E-02
+SLITRK1	3.22E-02
+SUV420H1	3.23E-02
+KCNH5	3.24E-02
+C17orf85	3.24E-02
+PYGB	3.25E-02
+NCKAP1	3.26E-02
+TNFRSF1A	3.27E-02
+PRDM1	3.27E-02
+SQSTM1	3.28E-02
+KCNJ1	3.29E-02
+STC2	3.29E-02
+CTCF	3.30E-02
+MYO1C	3.31E-02
+ZNFX1	3.31E-02
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+GABRG2	7.53E-02
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+NRIP1	7.54E-02
+C6orf106	7.55E-02
+TSHZ1	7.56E-02
+PRICKLE2	7.56E-02
+S1PR1	7.57E-02
+SLC12A2	7.58E-02
+NFIB	7.59E-02
+GABRB2	7.59E-02
+FERMT2	7.60E-02
+PMP22	7.61E-02
+ACVR1C	7.61E-02
+CEND1	7.62E-02
+CLVS1	7.63E-02
+PAX9	7.63E-02
+B4GALT5	7.64E-02
+TMEM204	7.65E-02
+DCAF10	7.65E-02
+EXOC1	7.66E-02
+LHX1	7.67E-02
+ECE2	7.67E-02
+NID1	7.68E-02
+MAP3K7	7.69E-02
+FBXO28	7.70E-02
+DSP	7.70E-02
+STAB2	7.71E-02
+SASH3	7.72E-02
+PRICKLE1	7.72E-02
+SLC5A1	7.73E-02
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+IGHMBP2	7.76E-02
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+ACTR2	7.79E-02
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+ACVR2A	7.81E-02
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+GLRA1	7.83E-02
+ACVRL1	7.83E-02
+GIMAP1	7.84E-02
+CLK2	7.85E-02
+CNNM2	7.85E-02
+CAMK1D	7.86E-02
+PSMD1	7.87E-02
+TNFSF8	7.87E-02
+ADCY7	7.88E-02
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+KCNA1	7.91E-02
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+NUP85	7.92E-02
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+TBL1X	8.03E-02
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+CLDN14	8.19E-02
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+COL4A4	8.25E-02
+KLK3	8.25E-02
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+HK2	8.28E-02
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+R3HDM2	8.29E-02
+KCNQ3	8.30E-02
+DAAM1	8.31E-02
+CSF2RB	8.32E-02
+WDR33	8.32E-02
+ICMT	8.33E-02
+C17orf62	8.34E-02
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+CA7	8.36E-02
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+DLGAP4	1.17E-01
+FOXO4	1.18E-01
+LDHD	1.18E-01
+TGFB3	1.18E-01
+TPTE2	1.18E-01
+MYO18A	1.18E-01
+TCF7L1	1.18E-01
+EIF6	1.18E-01
+TGM1	1.18E-01
+PSMC6	1.18E-01
+SNX27	1.18E-01
+NASP	1.18E-01
+EPHA4	1.18E-01
+ABCB8	1.18E-01
+MON1A	1.18E-01
+LZTS1	1.18E-01
+RGAG1	1.19E-01
+YLPM1	1.19E-01
+SLC5A10	1.19E-01
+MAGEB4	1.19E-01
+SERPINA7	1.19E-01
+PHYH	1.19E-01
+MTMR14	1.19E-01
+IL2RG	1.19E-01
+KIAA1045	1.19E-01
+TRA2B	1.19E-01
+IL4I1	1.19E-01
+MBTD1	1.19E-01
+E2F2	1.19E-01
+NPAS2	1.19E-01
+KCNH8	1.20E-01
+KRT16	1.20E-01
+RANBP10	1.20E-01
+SERPINH1	1.20E-01
+NUP54	1.20E-01
+NGFR	1.20E-01
+CNOT4	1.20E-01
+CLCNKB	1.20E-01
+SH3BP5	1.20E-01
+MAST1	1.20E-01
+FZD8	1.20E-01
+SEC23B	1.20E-01
+HOXB1	1.20E-01
+ST6GAL1	1.20E-01
+CYLC1	1.20E-01
+GK	1.21E-01
+PAPOLA	1.21E-01
+PDZD4	1.21E-01
+TAF12	1.21E-01
+APBB1	1.21E-01
+LPCAT4	1.21E-01
+RBM6	1.21E-01
+CHD8	1.21E-01
+CACNB1	1.21E-01
+HNRNPA2B1	1.21E-01
+AEBP2	1.21E-01
+MAK16	1.21E-01
+RCC1	1.21E-01
+NR1D2	1.21E-01
+JAKMIP2	1.22E-01
+POLR3H	1.22E-01
+SEPN1	1.22E-01
+EIF2B3	1.22E-01
+RP2	1.22E-01
+DLK1	1.22E-01
+ETFB	1.22E-01
+SP3	1.22E-01
+MATN4	1.22E-01
+ELAVL4	1.22E-01
+ZMYND11	1.22E-01
+PISD	1.22E-01
+SFTPC	1.22E-01
+KATNAL1	1.22E-01
+MGAT2	1.22E-01
+ATP1A4	1.23E-01
+ZNF24	1.23E-01
+PDGFRB	1.23E-01
+FOXN2	1.23E-01
+MYH4	1.23E-01
+TAB2	1.23E-01
+TBCEL	1.23E-01
+ITPKB	1.23E-01
+CFL1	1.23E-01
+ATP4A	1.23E-01
+CSHL1	1.23E-01
+BMP7	1.23E-01
+SLC32A1	1.23E-01
+HABP2	1.23E-01
+FBXO5	1.24E-01
+AIRE	1.24E-01
+DLG5	1.24E-01
+PDHB	1.24E-01
+ATP13A3	1.24E-01
+ADAR	1.24E-01
+EBF1	1.24E-01
+ARSE	1.24E-01
+GABRB3	1.24E-01
+TMEM100	1.24E-01
+CCR1	1.24E-01
+CALM2	1.24E-01
+NPNT	1.24E-01
+AGPS	1.24E-01
+C18orf25	1.24E-01
+CDC14B	1.25E-01
+RBM15B	1.25E-01
+INTS10	1.25E-01
+CDK6	1.25E-01
+PDGFRA	1.25E-01
+SLC5A6	1.25E-01
+PRSS1	1.25E-01
+PFKFB3	1.25E-01
+HPS4	1.25E-01
+F2	1.25E-01
+MAGEA11	1.25E-01
+EFEMP2	1.25E-01
+ARCN1	1.25E-01
+CD320	1.25E-01
+CHAF1A	1.26E-01
+SURF4	1.26E-01
+AMPD1	1.26E-01
+MYH1	1.26E-01
+E2F4	1.26E-01
+CAPN9	1.26E-01
+BSN	1.26E-01
+SOD1	1.26E-01
+SUPT16H	1.26E-01
+MAPK8	1.26E-01
+FZD1	1.26E-01
+FGG	1.26E-01
+RNF182	1.26E-01
+NR1H4	1.26E-01
+BTD	1.26E-01
+SLC45A4	1.27E-01
+CLIP2	1.27E-01
+TMOD1	1.27E-01
+SHOX2	1.27E-01
+ITGB3	1.27E-01
+LAX1	1.27E-01
+PPP4C	1.27E-01
+NDUFS7	1.27E-01
+NVL	1.27E-01
+MRPL43	1.27E-01
+LCAT	1.27E-01
+MASP1	1.27E-01
+BAG3	1.27E-01
+PTPN6	1.27E-01
+KIAA0907	1.28E-01
+IGF1	1.28E-01
+POGZ	1.28E-01
+ADAD1	1.28E-01
+TPSG1	1.28E-01
+SLC25A19	1.28E-01
+AQP6	1.28E-01
+HPRT1	1.28E-01
+DSN1	1.28E-01
+TNNI2	1.28E-01
+RAP1GAP2	1.28E-01
+LCK	1.28E-01
+GDA	1.28E-01
+CDKL5	1.28E-01
+RRAGB	1.28E-01
+PPP5C	1.29E-01
+SLC25A11	1.29E-01
+ATP13A1	1.29E-01
+ACTA2	1.29E-01
+DNM1L	1.29E-01
+MBNL3	1.29E-01
+PRIMA1	1.29E-01
+XBP1	1.29E-01
+REEP2	1.29E-01
+TET3	1.29E-01
+SLC3A1	1.29E-01
+HSD3B2	1.29E-01
+PARK7	1.29E-01
+HIST1H3C	1.29E-01
+TMEM57	1.30E-01
+ARL8A	1.30E-01
+HSD11B2	1.30E-01
+PRKCG	1.30E-01
+TBX20	1.30E-01
+KLK12	1.30E-01
+SSBP4	1.30E-01
+PAIP1	1.30E-01
+SLIT1	1.30E-01
+DGKG	1.30E-01
+SCARA3	1.30E-01
+METRNL	1.30E-01
+SYNGR1	1.30E-01
+CD247	1.30E-01
+TPH2	1.30E-01
+PHRF1	1.31E-01
+UBQLN2	1.31E-01
+HGF	1.31E-01
+GABRA5	1.31E-01
+ZRANB1	1.31E-01
+MFSD2A	1.31E-01
+HS3ST5	1.31E-01
+GRIPAP1	1.31E-01
+KCNS3	1.31E-01
+CPT2	1.31E-01
+SDHD	1.31E-01
+WASL	1.31E-01
+ABCA10	1.31E-01
+SPTBN1	1.31E-01
+CDC5L	1.32E-01
+CBLN4	1.32E-01
+TGFBI	1.32E-01
+RBMX	1.32E-01
+FGD1	1.32E-01
+PDS5B	1.32E-01
+SLCO3A1	1.32E-01
+PANK2	1.32E-01
+FBXL20	1.32E-01
+TNNT1	1.32E-01
+KCNG1	1.32E-01
+SPATS2	1.32E-01
+SIPA1L3	1.32E-01
+COPS7A	1.32E-01
+COL16A1	1.32E-01
+ALAD	1.33E-01
+C2CD2L	1.33E-01
+SEMA6A	1.33E-01
+HMGCS1	1.33E-01
+RSBN1L	1.33E-01
+XPO7	1.33E-01
+NXPH1	1.33E-01
+ALDOB	1.33E-01
+CHST3	1.33E-01
+HN1	1.33E-01
+ATP5A1	1.33E-01
+RBM15	1.33E-01
+LTA	1.33E-01
+PCYT2	1.33E-01
+BDH1	1.34E-01
+DAB2	1.34E-01
+ATXN7L3	1.34E-01
+SIPA1L2	1.34E-01
+KLK6	1.34E-01
+RASA1	1.34E-01
+ACAA1	1.34E-01
+TMPRSS6	1.34E-01
+CDK12	1.34E-01
+NOX1	1.34E-01
+ROS1	1.34E-01
+ZNRF3	1.34E-01
+CARHSP1	1.34E-01
+ADCY1	1.34E-01
+PDIK1L	1.34E-01
+SCML2	1.35E-01
+ACTL9	1.35E-01
+PAPOLG	1.35E-01
+DUOX2	1.35E-01
+TSHZ2	1.35E-01
+CCDC149	1.35E-01
+ADAMTS2	1.35E-01
+EIF4G1	1.35E-01
+TSHZ3	1.35E-01
+SLC17A7	1.35E-01
+GPRC6A	1.35E-01
+SLC7A8	1.35E-01
+NDE1	1.35E-01
+LONP1	1.35E-01
+GLIS1	1.36E-01
+TFDP1	1.36E-01
+TM9SF4	1.36E-01
+STRN3	1.36E-01
+IRF4	1.36E-01
+ATP11A	1.36E-01
+NIP7	1.36E-01
+HUWE1	1.36E-01
+RILPL2	1.36E-01
+NDUFAB1	1.36E-01
+ARSI	1.36E-01
+C10orf88	1.36E-01
+RNF185	1.36E-01
+OGDH	1.36E-01
+ZNF512B	1.36E-01
+S1PR2	1.37E-01
+SGSH	1.37E-01
+FOXS1	1.37E-01
+PSMB1	1.37E-01
+H2AFY	1.37E-01
+FBL	1.37E-01
+MEOX1	1.37E-01
+FOXH1	1.37E-01
+IL10RA	1.37E-01
+TGM6	1.37E-01
+LIMA1	1.37E-01
+COX5A	1.37E-01
+UMODL1	1.37E-01
+NIT1	1.37E-01
+CAPN6	1.38E-01
+TMEM51	1.38E-01
+EDC3	1.38E-01
+LRRTM1	1.38E-01
+GJA8	1.38E-01
+PLLP	1.38E-01
+ACP5	1.38E-01
+HBD	1.38E-01
+TLX1	1.38E-01
+ZNF704	1.38E-01
+GABBR2	1.38E-01
+ACVR1	1.38E-01
+NOTCH4	1.38E-01
+HOXA2	1.38E-01
+KIAA1191	1.38E-01
+TK2	1.39E-01
+MLLT6	1.39E-01
+SYT7	1.39E-01
+UBE2Q1	1.39E-01
+C7orf26	1.39E-01
+TMPRSS4	1.39E-01
+SLC39A10	1.39E-01
+AQP4	1.39E-01
+EHD3	1.39E-01
+DCAF5	1.39E-01
+ITPR2	1.39E-01
+CORO1A	1.39E-01
+AHCYL1	1.39E-01
+MYH8	1.39E-01
+RIC8B	1.40E-01
+CHERP	1.40E-01
+RXRB	1.40E-01
+LYPD2	1.40E-01
+AEBP1	1.40E-01
+GAMT	1.40E-01
+UCKL1	1.40E-01
+IL7	1.40E-01
+ATP1B1	1.40E-01
+KLK15	1.40E-01
+ZNF460	1.40E-01
+CLIC2	1.40E-01
+SLC5A2	1.40E-01
+RAD51	1.40E-01
+SDHB	1.40E-01
+SLC20A1	1.41E-01
+ELL2	1.41E-01
+MOSPD3	1.41E-01
+PRR19	1.41E-01
+FNBP4	1.41E-01
+TUBAL3	1.41E-01
+DAGLA	1.41E-01
+UTP14A	1.41E-01
+NLRP4	1.41E-01
+C5orf30	1.41E-01
+PSMC5	1.41E-01
+TNFAIP3	1.41E-01
+PSMA2	1.41E-01
+GJB4	1.41E-01
+TMEM190	1.42E-01
+ZBED1	1.42E-01
+KRT31	1.42E-01
+PHF6	1.42E-01
+AMELX	1.42E-01
+C20orf195	1.42E-01
+AP2A1	1.42E-01
+SRP68	1.42E-01
+HNRNPAB	1.42E-01
+PHTF2	1.42E-01
+ATP10A	1.42E-01
+CD2	1.42E-01
+TESK1	1.42E-01
+CLN8	1.42E-01
+KCNA7	1.42E-01
+SAMD4A	1.43E-01
+MARCH5	1.43E-01
+ITGB7	1.43E-01
+ENOX2	1.43E-01
+PLA2G15	1.43E-01
+MAT2A	1.43E-01
+LIPT1	1.43E-01
+VAX2	1.43E-01
+BCL9L	1.43E-01
+CCT8	1.43E-01
+CAPN2	1.43E-01
+TBX15	1.43E-01
+MYO5A	1.43E-01
+CCNYL1	1.43E-01
+SPTB	1.44E-01
+XPR1	1.44E-01
+ASPA	1.44E-01
+HGFAC	1.44E-01
+MYO1G	1.44E-01
+BCR	1.44E-01
+MCCC1	1.44E-01
+C2orf69	1.44E-01
+LAPTM5	1.44E-01
+CHRNB4	1.44E-01
+ING5	1.44E-01
+GRIK5	1.44E-01
+GPR85	1.44E-01
+CDKN2A	1.44E-01
+MOCS1	1.44E-01
+SARS	1.45E-01
+CLDN16	1.45E-01
+YWHAQ	1.45E-01
+RPGRIP1L	1.45E-01
+RBM33	1.45E-01
+WIPF1	1.45E-01
+CETN1	1.45E-01
+ASRGL1	1.45E-01
+SLC1A2	1.45E-01
+KBTBD2	1.45E-01
+DLG2	1.45E-01
+RNF166	1.45E-01
+PIGU	1.45E-01
+PURG	1.45E-01
+PPP1R9A	1.46E-01
+ATP6V1B2	1.46E-01
+ZCCHC14	1.46E-01
+BEND4	1.46E-01
+MAP4	1.46E-01
+ABCC5	1.46E-01
+PTCHD2	1.46E-01
+CPOX	1.46E-01
+LPCAT1	1.46E-01
+FLRT3	1.46E-01
+SGPP1	1.46E-01
+CLDN9	1.46E-01
+RUNX1	1.46E-01
+ALOXE3	1.46E-01
+TINF2	1.46E-01
+MLH3	1.47E-01
+EDNRA	1.47E-01
+DHRS4L2	1.47E-01
+ODC1	1.47E-01
+SYN3	1.47E-01
+GTF2A1	1.47E-01
+IRF9	1.47E-01
+RRM2B	1.47E-01
+SNX8	1.47E-01
+ERBB4	1.47E-01
+KRT74	1.47E-01
+KCNG4	1.47E-01
+EFNA1	1.47E-01
+STOX2	1.47E-01
+MST1	1.48E-01
+PPP4R4	1.48E-01
+RSPRY1	1.48E-01
+PTOV1	1.48E-01
+RNF41	1.48E-01
+CEPT1	1.48E-01
+COL19A1	1.48E-01
+SPINT1	1.48E-01
+DFFA	1.48E-01
+TMEM87A	1.48E-01
+UCN2	1.48E-01
+PPP1R14D	1.48E-01
+DDAH1	1.48E-01
+MYOG	1.48E-01
+CD40	1.48E-01
+ERBB2	1.49E-01
+CYGB	1.49E-01
+ARHGAP36	1.49E-01
+P2RY10	1.49E-01
+RRM1	1.49E-01
+NLGN4X	1.49E-01
+COMMD1	1.49E-01
+GNL1	1.49E-01
+FNDC3B	1.49E-01
+PCDH17	1.49E-01
+ABCA9	1.49E-01
+SIVA1	1.49E-01
+IL27	1.49E-01
+NFKBIB	1.49E-01
+HPCA	1.50E-01
+CHST6	1.50E-01
+CSF1R	1.50E-01
+ALX3	1.50E-01
+BCMO1	1.50E-01
+RNF10	1.50E-01
+FZD9	1.50E-01
+DNMT3A	1.50E-01
+RMND5A	1.50E-01
+PTPRO	1.50E-01
+FUT2	1.50E-01
+TCF25	1.50E-01
+SLIT3	1.50E-01
+AHSA1	1.50E-01
+ADRB3	1.50E-01
+STAT1	1.51E-01
+SLC4A11	1.51E-01
+VAX1	1.51E-01
+HDAC4	1.51E-01
+PHGDH	1.51E-01
+GLTPD1	1.51E-01
+CCDC106	1.51E-01
+CHST4	1.51E-01
+SMAD9	1.51E-01
+KIRREL3	1.51E-01
+STEAP3	1.51E-01
+GSTK1	1.51E-01
+PCGF1	1.51E-01
+ZNF654	1.51E-01
+PTP4A2	1.51E-01
+IL12A	1.52E-01
+ABCD4	1.52E-01
+PRSS3	1.52E-01
+TAF1	1.52E-01
+SMPD3	1.52E-01
+BATF	1.52E-01
+PDLIM7	1.52E-01
+POMT2	1.52E-01
+GPR50	1.52E-01
+UBE2E2	1.52E-01
+KCNN4	1.52E-01
+GPR37	1.52E-01
+P2RY8	1.52E-01
+CCNJ	1.52E-01
+HMGB1	1.53E-01
+CNGA4	1.53E-01
+NPHP3	1.53E-01
+MIB2	1.53E-01
+CATSPER4	1.53E-01
+CLIC5	1.53E-01
+USP22	1.53E-01
+ADO	1.53E-01
+CXorf21	1.53E-01
+HIST1H1B	1.53E-01
+GALK2	1.53E-01
+FGFR1OP2	1.53E-01
+ZMYND19	1.53E-01
+MATN2	1.53E-01
+PTCHD3	1.53E-01
+RUVBL2	1.54E-01
+TMPRSS3	1.54E-01
+SNCG	1.54E-01
+IVD	1.54E-01
+NUDT16L1	1.54E-01
+ITPK1	1.54E-01
+MEIS3	1.54E-01
+ZMIZ1	1.54E-01
+GUCA2B	1.54E-01
+KCNJ9	1.54E-01
+ARSF	1.54E-01
+MEST	1.54E-01
+PHF19	1.54E-01
+STAT2	1.54E-01
+COPS3	1.55E-01
+C11orf58	1.55E-01
+COL18A1	1.55E-01
+ACADM	1.55E-01
+TTF2	1.55E-01
+ATF7IP	1.55E-01
+ALX4	1.55E-01
+BCL6	1.55E-01
+ST8SIA2	1.55E-01
+TUBA1B	1.55E-01
+UCK2	1.55E-01
+COL6A6	1.55E-01
+KPNA6	1.55E-01
+LHX4	1.55E-01
+CNIH2	1.55E-01
+HRCT1	1.56E-01
+TASP1	1.56E-01
+PPP3CB	1.56E-01
+IPO5	1.56E-01
+ARMCX5	1.56E-01
+TLK2	1.56E-01
+FMNL2	1.56E-01
+MAX	1.56E-01
+SCUBE2	1.56E-01
+PNKD	1.56E-01
+AP2B1	1.56E-01
+ANTXR1	1.56E-01
+RAG1	1.56E-01
+CHST15	1.56E-01
+PSMD12	1.57E-01
+GSK3B	1.57E-01
+CFI	1.57E-01
+SLC26A3	1.57E-01
+CELSR1	1.57E-01
+BBS9	1.57E-01
+ANAPC2	1.57E-01
+ELL	1.57E-01
+EIF4EBP2	1.57E-01
+BRI3BP	1.57E-01
+NUDT3	1.57E-01
+GGNBP2	1.57E-01
+BRMS1	1.57E-01
+MPZ	1.57E-01
+IGFN1	1.57E-01
+EDAR	1.58E-01
+ZNF146	1.58E-01
+BCAR1	1.58E-01
+CBFB	1.58E-01
+SEC24C	1.58E-01
+ANKRD46	1.58E-01
+PPFIA2	1.58E-01
+ALDH3B2	1.58E-01
+ATG3	1.58E-01
+GDF5	1.58E-01
+CNGB1	1.58E-01
+PCSK2	1.58E-01
+AKAP14	1.58E-01
+SEMA3F	1.58E-01
+SERPINB5	1.59E-01
+KIAA0196	1.59E-01
+KLHL22	1.59E-01
+ALG8	1.59E-01
+JAK3	1.59E-01
+FLYWCH1	1.59E-01
+BARHL2	1.59E-01
+NCSTN	1.59E-01
+RBP4	1.59E-01
+NAA30	1.59E-01
+MBNL1	1.59E-01
+IQSEC1	1.59E-01
+PBX2	1.59E-01
+PRMT5	1.59E-01
+NAGLU	1.59E-01
+AMIGO2	1.60E-01
+HAGH	1.60E-01
+SLC4A1	1.60E-01
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+BTBD2	1.60E-01
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+KCNK5	1.60E-01
+PLXND1	1.60E-01
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+RAD54L	1.60E-01
+ATP6V0A2	1.61E-01
+FRMD6	1.61E-01
+KLKB1	1.61E-01
+ZNF629	1.61E-01
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+HOXB9	1.62E-01
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+PPTC7	1.63E-01
+SEMA4C	1.63E-01
+CUTA	1.63E-01
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+HOXD13	1.63E-01
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+PRKAG3	1.63E-01
+CHRNA1	1.63E-01
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+SLA	1.68E-01
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+KRT75	1.70E-01
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+ACADS	1.96E-01
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+SLC26A10	2.01E-01
+AFG3L2	2.01E-01
+CADM2	2.01E-01
+CCNB1IP1	2.01E-01
+GGT7	2.01E-01
+SPRYD3	2.01E-01
+PRKCD	2.01E-01
+PPP1R13B	2.01E-01
+CHAD	2.01E-01
+KIAA1737	2.01E-01
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+CORIN	2.01E-01
+DCAF4L1	2.01E-01
+BRD2	2.01E-01
+XYLT1	2.02E-01
+MMP2	2.02E-01
+GSTCD	2.02E-01
+LPGAT1	2.02E-01
+ALK	2.02E-01
+ZBTB47	2.02E-01
+HTR3A	2.02E-01
+ANK3	2.02E-01
+NPR2	2.02E-01
+CRCP	2.02E-01
+MAPKAPK2	2.02E-01
+DGKD	2.02E-01
+RAI1	2.02E-01
+SLC26A2	2.02E-01
+MORC3	2.02E-01
+TMEM72	2.03E-01
+RDX	2.03E-01
+HMGCR	2.03E-01
+MITF	2.03E-01
+DSCR3	2.03E-01
+MYO7B	2.03E-01
+GAL3ST1	2.03E-01
+TRAM1	2.03E-01
+TOX	2.03E-01
+DCLK3	2.03E-01
+TWISTNB	2.03E-01
+B4GALT1	2.03E-01
+MFSD6L	2.03E-01
+CTH	2.03E-01
+PPT1	2.04E-01
+BCKDHA	2.04E-01
+IL31	2.04E-01
+ZNF217	2.04E-01
+LUC7L	2.04E-01
+CLDN6	2.04E-01
+DISP2	2.04E-01
+NRXN2	2.04E-01
+MTA2	2.04E-01
+ZNF513	2.04E-01
+COPZ1	2.04E-01
+ATP8A1	2.04E-01
+TIMP1	2.04E-01
+SERPINB13	2.04E-01
+PGRMC1	2.04E-01
+NRARP	2.05E-01
+GPR45	2.05E-01
+SYNC	2.05E-01
+AFF2	2.05E-01
+IFFO1	2.05E-01
+HDGFRP3	2.05E-01
+MIOX	2.05E-01
+KLHDC10	2.05E-01
+RCE1	2.05E-01
+SULT1A1	2.05E-01
+ATL2	2.05E-01
+HRAS	2.05E-01
+SFTPA1	2.05E-01
+CDC42SE2	2.05E-01
+KIF1B	2.06E-01
+ADAM10	2.06E-01
+TMEM39B	2.06E-01
+AP2M1	2.06E-01
+UPP1	2.06E-01
+AMHR2	2.06E-01
+MCCC2	2.06E-01
+RAG2	2.06E-01
+KCNIP3	2.06E-01
+HOXB5	2.06E-01
+NKX6-3	2.06E-01
+MB	2.06E-01
+TNFRSF10D	2.06E-01
+G0S2	2.06E-01
+SPEN	2.06E-01
+ABLIM1	2.07E-01
+CD8B	2.07E-01
+PMM2	2.07E-01
+ECEL1	2.07E-01
+F11	2.07E-01
+KLF3	2.07E-01
+MEMO1	2.07E-01
+HEPHL1	2.07E-01
+DMWD	2.07E-01
+B3GNT2	2.07E-01
+KCTD16	2.07E-01
+KRT71	2.07E-01
+RIMKLA	2.07E-01
+MARCH6	2.07E-01
+NDUFS1	2.08E-01
+SIAE	2.08E-01
+RDH11	2.08E-01
+CATSPER3	2.08E-01
+SCO1	2.08E-01
+DGUOK	2.08E-01
+THYN1	2.08E-01
+SH3GLB1	2.08E-01
+KATNAL2	2.08E-01
+GRIK4	2.08E-01
+HSD17B13	2.08E-01
+RNF213	2.08E-01
+TPSD1	2.08E-01
+CTNNB1	2.08E-01
+PEAR1	2.08E-01
+FGF12	2.09E-01
+SERPINB9	2.09E-01
+MYOC	2.09E-01
+SLC6A3	2.09E-01
+CLDN18	2.09E-01
+HSF4	2.09E-01
+ADD3	2.09E-01
+LMO3	2.09E-01
+TYK2	2.09E-01
+ARPP19	2.09E-01
+PKIB	2.09E-01
+LRRC7	2.09E-01
+DOK4	2.09E-01
+DHRS1	2.09E-01
+SERPINB3	2.10E-01
+DMRTC2	2.10E-01
+KRT20	2.10E-01
+GHR	2.10E-01
+CLDN1	2.10E-01
+KRTAP21-1	2.10E-01
+MTHFR	2.10E-01
+MRE11A	2.10E-01
+ANAPC11	2.10E-01
+PRICKLE3	2.10E-01
+FAM102A	2.10E-01
+SF3A1	2.10E-01
+KLF7	2.10E-01
+EPHB3	2.10E-01
+FAF2	2.10E-01
+NIPAL4	2.11E-01
+C1QB	2.11E-01
+PLG	2.11E-01
+TNFRSF11B	2.11E-01
+ACLY	2.11E-01
+PRSS23	2.11E-01
+TAF15	2.11E-01
+KIAA1598	2.11E-01
+ATP5D	2.11E-01
+SLC25A12	2.11E-01
+TRIM32	2.11E-01
+MTF1	2.11E-01
+C1orf43	2.11E-01
+SPATA5L1	2.11E-01
+JHDM1D	2.12E-01
+BDNF	2.12E-01
+SCD	2.12E-01
+PLA1A	2.12E-01
+EIF2S1	2.12E-01
+TCEAL2	2.12E-01
+PI4KB	2.12E-01
+OXCT1	2.12E-01
+AGPAT4	2.12E-01
+BCL2L14	2.12E-01
+HOXA9	2.12E-01
+PCDH9	2.12E-01
+MPPED1	2.12E-01
+PTMA	2.12E-01
+RNF130	2.12E-01
+ZFP91	2.13E-01
+PDYN	2.13E-01
+WDR37	2.13E-01
+SERPINA11	2.13E-01
+MAN1A2	2.13E-01
+CDKN1B	2.13E-01
+C19orf54	2.13E-01
+PANK1	2.13E-01
+VPS4B	2.13E-01
+FAM169A	2.13E-01
+ZNF496	2.13E-01
+GDAP1	2.13E-01
+LRRC41	2.13E-01
+CCRN4L	2.13E-01
+AGPAT1	2.14E-01
+CYC1	2.14E-01
+TRIP4	2.14E-01
+TNNT3	2.14E-01
+RCAN1	2.14E-01
+STAG1	2.14E-01
+EIF3I	2.14E-01
+HNF4G	2.14E-01
+LONRF3	2.14E-01
+FAM155A	2.14E-01
+KRTAP12-3	2.14E-01
+PDGFC	2.14E-01
+CAPN5	2.14E-01
+FMNL3	2.14E-01
+ATP11C	2.14E-01
+HOXA1	2.15E-01
+TLE1	2.15E-01
+GPAA1	2.15E-01
+PLK1	2.15E-01
+UGCG	2.15E-01
+CISD2	2.15E-01
+JPH1	2.15E-01
+BMP15	2.15E-01
+PRSS38	2.15E-01
+CRADD	2.15E-01
+P4HTM	2.15E-01
+C19orf44	2.15E-01
+VPS28	2.15E-01
+C5orf15	2.15E-01
+RCAN2	2.16E-01
+HTR1D	2.16E-01
+TMCC2	2.16E-01
+FAM19A2	2.16E-01
+CLPP	2.16E-01
+HOXA11	2.16E-01
+PPAT	2.16E-01
+KRT23	2.16E-01
+SDC3	2.16E-01
+U2AF2	2.16E-01
+DNAJB1	2.16E-01
+NAGS	2.16E-01
+ZC3H18	2.16E-01
+HAND1	2.16E-01
+PRRG4	2.16E-01
+CREB5	2.17E-01
+SLC2A10	2.17E-01
+MATR3	2.17E-01
+EIF3J	2.17E-01
+RNF138	2.17E-01
+TMEM19	2.17E-01
+SYCE2	2.17E-01
+TCEAL5	2.17E-01
+RTN1	2.17E-01
+TELO2	2.17E-01
+TAL2	2.17E-01
+NFYA	2.17E-01
+ARHGEF1	2.17E-01
+FOXD4L1	2.17E-01
+GXYLT1	2.17E-01
+TNFRSF13B	2.18E-01
+QSER1	2.18E-01
+HOXC10	2.18E-01
+REV3L	2.18E-01
+RNF152	2.18E-01
+BFSP2	2.18E-01
+STOML3	2.18E-01
+MYL3	2.18E-01
+MKL1	2.18E-01
+HBP1	2.18E-01
+FLT3	2.18E-01
+SLC4A5	2.18E-01
+IKZF4	2.18E-01
+ARSK	2.18E-01
+ATG9A	2.19E-01
+OLFM1	2.19E-01
+CRBN	2.19E-01
+PGAP1	2.19E-01
+EFNB3	2.19E-01
+TARBP2	2.19E-01
+ATP5J	2.19E-01
+KCNE3	2.19E-01
+TGFB1	2.19E-01
+MOBP	2.19E-01
+PRKG2	2.19E-01
+GPR20	2.19E-01
+MAMSTR	2.19E-01
+CD81	2.19E-01
+HMX2	2.19E-01
+TNNC1	2.20E-01
+ZFC3H1	2.20E-01
+HNRNPA1	2.20E-01
+STRN4	2.20E-01
+ZBTB4	2.20E-01
+CHML	2.20E-01
+DYRK1A	2.20E-01
+RSRC2	2.20E-01
+MYT1	2.20E-01
+PCBP2	2.20E-01
+CMIP	2.20E-01
+RAC1	2.20E-01
+TBX6	2.20E-01
+RGMB	2.20E-01
+NUDT10	2.21E-01
+SLC5A8	2.21E-01
+MAB21L2	2.21E-01
+SERPINB2	2.21E-01
+PLCG2	2.21E-01
+SYS1	2.21E-01
+AGAP3	2.21E-01
+ATP6V1A	2.21E-01
+KRT39	2.21E-01
+CNGB3	2.21E-01
+CAT	2.21E-01
+SGPP2	2.21E-01
+MSGN1	2.21E-01
+UCHL1	2.21E-01
+T	2.21E-01
+ASXL3	2.22E-01
+C3orf58	2.22E-01
+DIAPH2	2.22E-01
+RNF11	2.22E-01
+SPCS2	2.22E-01
+PPP1CB	2.22E-01
+SEC24B	2.22E-01
+NEU2	2.22E-01
+ARHGDIA	2.22E-01
+FGR	2.22E-01
+HLX	2.22E-01
+ATF7	2.22E-01
+JMY	2.22E-01
+OLFML1	2.22E-01
+TCTN3	2.23E-01
+ARSH	2.23E-01
+C15orf40	2.23E-01
+RNF2	2.23E-01
+HSD11B1	2.23E-01
+ADIPOR1	2.23E-01
+HELLS	2.23E-01
+VAC14	2.23E-01
+EPHA7	2.23E-01
+COPS8	2.23E-01
+SIX6	2.23E-01
+ITGB6	2.23E-01
+NCK2	2.23E-01
+NAP1L4	2.23E-01
+PLEKHH3	2.23E-01
+PLEKHF1	2.24E-01
+MKLN1	2.24E-01
+TBC1D20	2.24E-01
+CDC40	2.24E-01
+FNDC5	2.24E-01
+MMEL1	2.24E-01
+GATAD2A	2.24E-01
+AXIN2	2.24E-01
+DDI2	2.24E-01
+MX1	2.24E-01
+RASGEF1A	2.24E-01
+CXorf65	2.24E-01
+ERP29	2.24E-01
+CNN2	2.24E-01
+PHF7	2.25E-01
+SYT2	2.25E-01
+PCDH1	2.25E-01
+AP3D1	2.25E-01
+ARL4A	2.25E-01
+SNRPD2	2.25E-01
+RCC2	2.25E-01
+TRPC6	2.25E-01
+CPEB4	2.25E-01
+LPXN	2.25E-01
+GPR158	2.25E-01
+POLR2H	2.25E-01
+EMCN	2.25E-01
+FER1L6	2.25E-01
+SCD5	2.25E-01
+STX6	2.26E-01
+BRD3	2.26E-01
+PYY	2.26E-01
+PKIG	2.26E-01
+TGM5	2.26E-01
+ATXN7L2	2.26E-01
+PRKAB2	2.26E-01
+CDH22	2.26E-01
+WNT11	2.26E-01
+DUSP10	2.26E-01
+PQBP1	2.26E-01
+SHBG	2.26E-01
+FGF13	2.26E-01
+MPND	2.26E-01
+TTC17	2.27E-01
+PHC3	2.27E-01
+SERPINA3	2.27E-01
+AQP7	2.27E-01
+RFT1	2.27E-01
+BEST3	2.27E-01
+PIK3R5	2.27E-01
+ATP9B	2.27E-01
+GRIK1	2.27E-01
+SOS2	2.27E-01
+GPR12	2.27E-01
+GINS3	2.27E-01
+CX3CL1	2.27E-01
+AKAP8L	2.27E-01
+MANEA	2.27E-01
+SPDEF	2.28E-01
+UBE2G1	2.28E-01
+IPMK	2.28E-01
+IQSEC2	2.28E-01
+TMEM222	2.28E-01
+CAV2	2.28E-01
+FRMD3	2.28E-01
+IRF3	2.28E-01
+TMLHE	2.28E-01
+BIVM	2.28E-01
+VASP	2.28E-01
+NAV3	2.28E-01
+CELSR2	2.28E-01
+DRGX	2.28E-01
+TMEM180	2.29E-01
+GJA10	2.29E-01
+CDA	2.29E-01
+PUM1	2.29E-01
+HSD17B3	2.29E-01
+HIST1H3F	2.29E-01
+VEGFC	2.29E-01
+ZBTB10	2.29E-01
+FBLIM1	2.29E-01
+HSPB8	2.29E-01
+TECTA	2.29E-01
+C9orf142	2.29E-01
+IKZF5	2.29E-01
+ISX	2.29E-01
+HDAC7	2.29E-01
+CDH20	2.30E-01
+SLC7A11	2.30E-01
+TIPRL	2.30E-01
+NDN	2.30E-01
+CHRND	2.30E-01
+RAB8A	2.30E-01
+PTMS	2.30E-01
+PNPLA7	2.30E-01
+SIT1	2.30E-01
+DIAPH3	2.30E-01
+MXD1	2.30E-01
+FAM78A	2.30E-01
+ANGPT2	2.30E-01
+GDF11	2.30E-01
+PCDH7	2.31E-01
+PCDH20	2.31E-01
+EVI5L	2.31E-01
+PAXIP1	2.31E-01
+PRKAR2A	2.31E-01
+BCKDHB	2.31E-01
+TNRC6A	2.31E-01
+DGKH	2.31E-01
+C1QC	2.31E-01
+FAM177A1	2.31E-01
+DNAJC28	2.31E-01
+CLN3	2.31E-01
+POU1F1	2.31E-01
+MYO3B	2.31E-01
+PTDSS2	2.31E-01
+SNAI1	2.32E-01
+AMY2B	2.32E-01
+DCUN1D4	2.32E-01
+NIPAL3	2.32E-01
+NDFIP1	2.32E-01
+DYNLRB1	2.32E-01
+PCDH10	2.32E-01
+TSNAX	2.32E-01
+GLUD1	2.32E-01
+KRT27	2.32E-01
+CDKN1A	2.32E-01
+LGR6	2.32E-01
+MYLIP	2.32E-01
+GRIN3A	2.32E-01
+HSD17B4	2.33E-01
+BBS2	2.33E-01
+CHMP1A	2.33E-01
+ABCD2	2.33E-01
+AHCTF1	2.33E-01
+DICER1	2.33E-01
+EGR2	2.33E-01
+PLAGL2	2.33E-01
+SIN3B	2.33E-01
+RUVBL1	2.33E-01
+TRAPPC3	2.33E-01
+GATSL3	2.33E-01
+C1orf216	2.33E-01
+PPFIA1	2.33E-01
+MAPK10	2.33E-01
+CCDC89	2.34E-01
+MYO16	2.34E-01
+KRT24	2.34E-01
+RNLS	2.34E-01
+CDC23	2.34E-01
+CABP7	2.34E-01
+SELT	2.34E-01
+TSPAN5	2.34E-01
+KEL	2.34E-01
+MAP3K8	2.34E-01
+C10orf137	2.34E-01
+PRLR	2.34E-01
+PEX10	2.34E-01
+TMEM168	2.34E-01
+INSIG2	2.35E-01
+FIP1L1	2.35E-01
+SUCLG1	2.35E-01
+SERPINB4	2.35E-01
+KCNA3	2.35E-01
+PARD6G	2.35E-01
+SNRPD3	2.35E-01
+CRISPLD2	2.35E-01
+HP	2.35E-01
+ANAPC7	2.35E-01
+QTRT1	2.35E-01
+CRTC2	2.35E-01
+PCSK4	2.35E-01
+CCBL1	2.35E-01
+C16orf70	2.35E-01
+MSL1	2.36E-01
+SMCHD1	2.36E-01
+NAA25	2.36E-01
+PAK4	2.36E-01
+MGLL	2.36E-01
+JMJD6	2.36E-01
+SAMD14	2.36E-01
+TLE4	2.36E-01
+BRMS1L	2.36E-01
+AWAT2	2.36E-01
+MSTN	2.36E-01
+FBXO8	2.36E-01
+FGF14	2.36E-01
+OMG	2.36E-01
+MFN1	2.37E-01
+PRND	2.37E-01
+EYA3	2.37E-01
+CAPZA3	2.37E-01
+KIF1C	2.37E-01
+BMP4	2.37E-01
+PDE8B	2.37E-01
+HN1L	2.37E-01
+SMCR8	2.37E-01
+TM2D3	2.37E-01
+PAPL	2.37E-01
+TNFRSF8	2.37E-01
+LGI4	2.37E-01
+ST3GAL2	2.37E-01
+C12orf56	2.37E-01
+PRPF38B	2.38E-01
+CD22	2.38E-01
+ADIPOR2	2.38E-01
+ABCB10	2.38E-01
+PRRG1	2.38E-01
+BCL2	2.38E-01
+WFIKKN2	2.38E-01
+ZNF644	2.38E-01
+NFATC2	2.38E-01
+ZP3	2.38E-01
+TATDN1	2.38E-01
+COCH	2.38E-01
+MSI2	2.38E-01
+EPOR	2.38E-01
+MEGF11	2.39E-01
+INSRR	2.39E-01
+SLC34A3	2.39E-01
+FAH	2.39E-01
+FAM131B	2.39E-01
+ZNF768	2.39E-01
+NOL12	2.39E-01
+PPRC1	2.39E-01
+RSPH9	2.39E-01
+FOXD4	2.39E-01
+ARHGAP31	2.39E-01
+PTHLH	2.39E-01
+SMURF1	2.39E-01
+SGCZ	2.39E-01
+FAM111A	2.39E-01
+RBM27	2.40E-01
+NPTX1	2.40E-01
+SLC7A13	2.40E-01
+SLC35A2	2.40E-01
+FUNDC2	2.40E-01
+TRAPPC10	2.40E-01
+SH3BP5L	2.40E-01
+ZBTB46	2.40E-01
+SMG6	2.40E-01
+TRIM24	2.40E-01
+AMICA1	2.40E-01
+PRR5L	2.40E-01
+KLHL4	2.40E-01
+ORMDL2	2.40E-01
+GRHL2	2.41E-01
+BEND5	2.41E-01
+EPHB6	2.41E-01
+VPS52	2.41E-01
+GRK5	2.41E-01
+DDX46	2.41E-01
+LIPI	2.41E-01
+AXL	2.41E-01
+RASAL2	2.41E-01
+ARHGEF6	2.41E-01
+PSMC4	2.41E-01
+ARHGEF12	2.41E-01
+NT5C1A	2.41E-01
+SLC6A8	2.41E-01
+KIF4A	2.41E-01
+ATP13A4	2.42E-01
+VPS29	2.42E-01
+FRMD5	2.42E-01
+SLC35C2	2.42E-01
+MFSD5	2.42E-01
+SMO	2.42E-01
+CAMKV	2.42E-01
+IMPAD1	2.42E-01
+VWC2L	2.42E-01
+IRAK1	2.42E-01
+PLOD3	2.42E-01
+VPS72	2.42E-01
+EAF1	2.42E-01
+SECISBP2L	2.42E-01
+LRRC25	2.43E-01
+SDS	2.43E-01
+DRG1	2.43E-01
+NEUROD4	2.43E-01
+FNIP2	2.43E-01
+MAN2A1	2.43E-01
+GPT2	2.43E-01
+TMEM109	2.43E-01
+RAI2	2.43E-01
+MUC5B	2.43E-01
+RAB1B	2.43E-01
+TM9SF2	2.43E-01
+TTPAL	2.43E-01
+QDPR	2.43E-01
+E2F7	2.43E-01
+TUBB3	2.44E-01
+TAT	2.44E-01
+FRRS1	2.44E-01
+TSPAN18	2.44E-01
+DACT1	2.44E-01
+SLC6A17	2.44E-01
+OTUB1	2.44E-01
+VGLL4	2.44E-01
+ADCY3	2.44E-01
+WDR76	2.44E-01
+ACTA1	2.44E-01
+MRPL54	2.44E-01
+HS6ST3	2.44E-01
+BAZ2B	2.44E-01
+VEGFB	2.45E-01
+BAZ1B	2.45E-01
+CTRL	2.45E-01
+OIT3	2.45E-01
+MAGOH	2.45E-01
+GEMIN7	2.45E-01
+C21orf62	2.45E-01
+MRPL33	2.45E-01
+PPM1E	2.45E-01
+POLR1D	2.45E-01
+XIAP	2.45E-01
+NFIC	2.45E-01
+JOSD1	2.45E-01
+AHCY	2.45E-01
+ETFA	2.45E-01
+LRRTM2	2.46E-01
+TIMP4	2.46E-01
+OLFM4	2.46E-01
+AUP1	2.46E-01
+NTNG2	2.46E-01
+KIAA1257	2.46E-01
+SPAG5	2.46E-01
+SECTM1	2.46E-01
+CPLX3	2.46E-01
+MTOR	2.46E-01
+CALML3	2.46E-01
+OXSM	2.46E-01
+VEZF1	2.46E-01
+NPAS4	2.46E-01
+SRFBP1	2.47E-01
+COPS6	2.47E-01
+ZNF532	2.47E-01
+NUP214	2.47E-01
+TET1	2.47E-01
+NUP50	2.47E-01
+SNAP29	2.47E-01
+TSTA3	2.47E-01
+MESDC2	2.47E-01
+SAMHD1	2.47E-01
+ARFRP1	2.47E-01
+FBXL7	2.47E-01
+AP1G1	2.47E-01
+CMAS	2.47E-01
+MTMR6	2.47E-01
+C8orf46	2.48E-01
+DNAJB14	2.48E-01
+SERTAD1	2.48E-01
+C14orf166	2.48E-01
+ALPI	2.48E-01
+RELA	2.48E-01
+TGM2	2.48E-01
+ATXN10	2.48E-01
+SULT1A2	2.48E-01
+PLAU	2.48E-01
+YPEL4	2.48E-01
+TF	2.48E-01
+SLC16A14	2.48E-01
+DNAJC14	2.48E-01
+BBS10	2.49E-01
+LIPG	2.49E-01
+FGF7	2.49E-01
+UQCRFS1	2.49E-01
+TYRO3	2.49E-01
+CDC42EP3	2.49E-01
+ESX1	2.49E-01
+PAK2	2.49E-01
+ACTR10	2.49E-01
+ELOVL5	2.49E-01
+MED9	2.49E-01
+CRIM1	2.49E-01
+SHC3	2.49E-01
+KIAA0895L	2.49E-01
+RNF103	2.49E-01
+C2orf42	2.50E-01
+C16orf91	2.50E-01
+PPM1L	2.50E-01
+CYB5R2	2.50E-01
+ATP5J2	2.50E-01
+BCL9	2.50E-01
+ZNF622	2.50E-01
+LATS1	2.50E-01
+ARSJ	2.50E-01
+MRPL21	2.50E-01
+SPRED1	2.50E-01
+PIGF	2.50E-01
+NXF1	2.50E-01
+BHLHB9	2.50E-01
+TMEM205	2.50E-01
+RBPMS2	2.51E-01
+CARD11	2.51E-01
+SNX3	2.51E-01
+FITM1	2.51E-01
+OVOL2	2.51E-01
+CTSS	2.51E-01
+CTDP1	2.51E-01
+SLITRK4	2.51E-01
+HS2ST1	2.51E-01
+NPHS2	2.51E-01
+PRSS50	2.51E-01
+ALDH3A2	2.51E-01
+SNIP1	2.51E-01
+CDK2	2.51E-01
+MRPL42	2.52E-01
+SPTLC3	2.52E-01
+MEF2B	2.52E-01
+NPY	2.52E-01
+KCNJ8	2.52E-01
+LACE1	2.52E-01
+CDH4	2.52E-01
+GMPS	2.52E-01
+BRPF1	2.52E-01
+PHF1	2.52E-01
+GALC	2.52E-01
+ZC3H12B	2.52E-01
+IL1B	2.52E-01
+IPO9	2.52E-01
+KLK4	2.52E-01
+MRPL41	2.53E-01
+GDAP1L1	2.53E-01
+GABRA3	2.53E-01
+PROP1	2.53E-01
+KCTD13	2.53E-01
+LDOC1L	2.53E-01
+ERLIN2	2.53E-01
+DGKA	2.53E-01
+GMEB1	2.53E-01
+AK5	2.53E-01
+MAP1B	2.53E-01
+LOX	2.53E-01
+DDX1	2.53E-01
+CUL7	2.53E-01
+DYNC1LI2	2.54E-01
+TRIO	2.54E-01
+EPC2	2.54E-01
+CCNI	2.54E-01
+CD28	2.54E-01
+CCBE1	2.54E-01
+FAHD1	2.54E-01
+KIF3C	2.54E-01
+HSDL1	2.54E-01
+FER	2.54E-01
+AES	2.54E-01
+ORMDL3	2.54E-01
+RNASEH2A	2.54E-01
+ZHX1	2.54E-01
+GALK1	2.54E-01
+ZFAND1	2.55E-01
+KIAA0895	2.55E-01
+FOS	2.55E-01
+ATAD1	2.55E-01
+TMEM161A	2.55E-01
+PLAGL1	2.55E-01
+EPB41L4A	2.55E-01
+RAPGEF2	2.55E-01
+FOXN4	2.55E-01
+GAR1	2.55E-01
+FAM19A1	2.55E-01
+ALOX5	2.55E-01
+CIR1	2.55E-01
+CRYAA	2.55E-01
+KRTAP19-7	2.56E-01
+MFAP2	2.56E-01
+SDSL	2.56E-01
+GPR4	2.56E-01
+RAPSN	2.56E-01
+PNLIP	2.56E-01
+MSC	2.56E-01
+ENSA	2.56E-01
+PRRC1	2.56E-01
+DENND1A	2.56E-01
+SPARC	2.56E-01
+C8orf33	2.56E-01
+OSBP	2.56E-01
+GSS	2.56E-01
+SFTPB	2.56E-01
+B3GALT2	2.57E-01
+EHD1	2.57E-01
+SLC25A23	2.57E-01
+TBX10	2.57E-01
+ABHD13	2.57E-01
+ALOX12B	2.57E-01
+DLX6	2.57E-01
+PDAP1	2.57E-01
+TMEM215	2.57E-01
+RBM42	2.57E-01
+NAGA	2.57E-01
+FBXO32	2.57E-01
+SPATA13	2.57E-01
+DSCAML1	2.57E-01
+MAP4K4	2.58E-01
+RBM26	2.58E-01
+FGF1	2.58E-01
+HSPB2	2.58E-01
+WDR7	2.58E-01
+CRB3	2.58E-01
+CACNA2D1	2.58E-01
+NRN1L	2.58E-01
+CLDN4	2.58E-01
+PIGV	2.58E-01
+NADSYN1	2.58E-01
+CD79A	2.58E-01
+AZU1	2.58E-01
+SLC19A2	2.58E-01
+VWA2	2.58E-01
+CD70	2.59E-01
+RBM4B	2.59E-01
+ARID2	2.59E-01
+IGLON5	2.59E-01
+NPY1R	2.59E-01
+BNIP3L	2.59E-01
+RELL1	2.59E-01
+CYP46A1	2.59E-01
+ACTBL2	2.59E-01
+PSPC1	2.59E-01
+B4GALT2	2.59E-01
+HSP90AB1	2.59E-01
+CRELD2	2.59E-01
+PIAS3	2.59E-01
+SLA2	2.60E-01
+C2	2.60E-01
+HP1BP3	2.60E-01
+TXN	2.60E-01
+KPNA1	2.60E-01
+ZCCHC6	2.60E-01
+AFF4	2.60E-01
+BAG1	2.60E-01
+LATS2	2.60E-01
+BAHD1	2.60E-01
+MDGA2	2.60E-01
+POLR2A	2.60E-01
+H2AFV	2.60E-01
+A4GNT	2.60E-01
+MX2	2.60E-01
+DONSON	2.61E-01
+SLC10A3	2.61E-01
+TNFRSF11A	2.61E-01
+C11orf88	2.61E-01
+PROZ	2.61E-01
+ITK	2.61E-01
+DCHS1	2.61E-01
+TEX13B	2.61E-01
+CSRP1	2.61E-01
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+RALY	2.61E-01
+THOC7	2.61E-01
+KRT4	2.61E-01
+PAK7	2.61E-01
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+LGI3	2.62E-01
+UPRT	2.62E-01
+NDUFA10	2.62E-01
+PDE9A	2.62E-01
+ACOT8	2.62E-01
+TANC2	2.62E-01
+ACHE	2.62E-01
+C1RL	2.62E-01
+CREB3L3	2.62E-01
+GNS	2.62E-01
+IFT52	2.62E-01
+FAM20B	2.62E-01
+SLC22A17	2.62E-01
+PCID2	2.62E-01
+NIPA1	2.63E-01
+GOLPH3	2.63E-01
+TCTN1	2.63E-01
+NDUFB6	2.63E-01
+GLDN	2.63E-01
+MBNL2	2.63E-01
+SLC25A6	2.63E-01
+SPATA2	2.63E-01
+SENP2	2.63E-01
+RNGTT	2.63E-01
+ARL5B	2.63E-01
+ATP13A5	2.63E-01
+RAC3	2.63E-01
+DCK	2.63E-01
+H3F3A	2.64E-01
+TROVE2	2.64E-01
+SRRM5	2.64E-01
+RAB7L1	2.64E-01
+MAP3K9	2.64E-01
+MYOD1	2.64E-01
+HIST1H2AC	2.64E-01
+ATP6V1B1	2.64E-01
+DCTN3	2.64E-01
+PTRH2	2.64E-01
+HIST1H2BN	2.64E-01
+CA11	2.64E-01
+ZBED2	2.64E-01
+SMURF2	2.64E-01
+ZBTB8OS	2.64E-01
+RPRD1B	2.65E-01
+INCA1	2.65E-01
+AGPAT6	2.65E-01
+RABGAP1	2.65E-01
+CXorf22	2.65E-01
+AFTPH	2.65E-01
+IPPK	2.65E-01
+FANCI	2.65E-01
+TPRX1	2.65E-01
+TMEM91	2.65E-01
+CD93	2.65E-01
+MPI	2.65E-01
+MYO3A	2.65E-01
+MKKS	2.65E-01
+TRIM2	2.66E-01
+SHPRH	2.66E-01
+MED8	2.66E-01
+ACTR1A	2.66E-01
+PERP	2.66E-01
+WDR47	2.66E-01
+PLEKHM3	2.66E-01
+TBC1D9	2.66E-01
+ING2	2.66E-01
+BMP3	2.66E-01
+LEFTY2	2.66E-01
+ITM2A	2.66E-01
+HOXD4	2.66E-01
+SLC35F1	2.66E-01
+AATF	2.66E-01
+TAOK2	2.67E-01
+TMEM163	2.67E-01
+DPYS	2.67E-01
+MARCO	2.67E-01
+KRT25	2.67E-01
+GCN1L1	2.67E-01
+TNP1	2.67E-01
+TMEM181	2.67E-01
+DPP4	2.67E-01
+LY6E	2.67E-01
+MYD88	2.67E-01
+SLTM	2.67E-01
+ACR	2.67E-01
+NOS1AP	2.67E-01
+ZDHHC14	2.68E-01
+CACNG7	2.68E-01
+RNF180	2.68E-01
+IRF1	2.68E-01
+DAB1	2.68E-01
+NTNG1	2.68E-01
+SRM	2.68E-01
+PIK3CA	2.68E-01
+SCLY	2.68E-01
+SCN2B	2.68E-01
+TLN1	2.68E-01
+TSNAXIP1	2.68E-01
+FAM171A1	2.68E-01
+TMED2	2.68E-01
+FAM50B	2.68E-01
+ACY3	2.69E-01
+BOLA3	2.69E-01
+DGCR2	2.69E-01
+PIP5K1C	2.69E-01
+C7orf50	2.69E-01
+ANKS1B	2.69E-01
+STIM1	2.69E-01
+SH2D5	2.69E-01
+CACNG5	2.69E-01
+EPS15L1	2.69E-01
+TMEM63C	2.69E-01
+ZNF185	2.69E-01
+TSSK2	2.69E-01
+ZNF710	2.69E-01
+SLC9A7	2.70E-01
+PDHA2	2.70E-01
+INPP4A	2.70E-01
+PALM	2.70E-01
+PROS1	2.70E-01
+MCOLN1	2.70E-01
+IL23A	2.70E-01
+EDIL3	2.70E-01
+BUB3	2.70E-01
+DCAF12L2	2.70E-01
+DIAPH1	2.70E-01
+PRSS36	2.70E-01
+DYNLL1	2.70E-01
+MAPK4	2.70E-01
+TSPAN9	2.70E-01
+CDK5RAP1	2.71E-01
+GTPBP1	2.71E-01
+NAT6	2.71E-01
+DDB1	2.71E-01
+TLR7	2.71E-01
+TMEM80	2.71E-01
+ALDH1A1	2.71E-01
+APRT	2.71E-01
+MMAB	2.71E-01
+PCSK1	2.71E-01
+FNDC4	2.71E-01
+COL23A1	2.71E-01
+TMEM74	2.71E-01
+PHTF1	2.71E-01
+PHF3	2.72E-01
+NEURL4	2.72E-01
+PRKCH	2.72E-01
+ATP5G3	2.72E-01
+NODAL	2.72E-01
+SCAMP2	2.72E-01
+TSHR	2.72E-01
+CD151	2.72E-01
+TP53I13	2.72E-01
+MRPS18A	2.72E-01
+PRDM4	2.72E-01
+CYP2U1	2.72E-01
+PPAPDC2	2.72E-01
+PPP6C	2.72E-01
+RIMKLB	2.72E-01
+PSMD8	2.73E-01
+PARVG	2.73E-01
+ALG13	2.73E-01
+SETD7	2.73E-01
+C1QBP	2.73E-01
+HGD	2.73E-01
+MASP2	2.73E-01
+C6	2.73E-01
+PLEKHA5	2.73E-01
+USF1	2.73E-01
+MAP3K11	2.73E-01
+MYL4	2.73E-01
+TNFSF4	2.73E-01
+FLYWCH2	2.73E-01
+CASP8	2.74E-01
+KDM4A	2.74E-01
+SLC44A1	2.74E-01
+IPO13	2.74E-01
+CCNG1	2.74E-01
+PGAM5	2.74E-01
+TMX2	2.74E-01
+EPHB4	2.74E-01
+TSKU	2.74E-01
+ARNT2	2.74E-01
+NCL	2.74E-01
+MAB21L1	2.74E-01
+ZRANB2	2.74E-01
+FAM76B	2.74E-01
+SF3B3	2.74E-01
+ABCG8	2.75E-01
+SIKE1	2.75E-01
+POFUT2	2.75E-01
+THAP9	2.75E-01
+NLRP12	2.75E-01
+DCBLD1	2.75E-01
+MDFI	2.75E-01
+TNFRSF12A	2.75E-01
+SENP5	2.75E-01
+LPAR4	2.75E-01
+KIAA1467	2.75E-01
+C8A	2.75E-01
+PRPF38A	2.75E-01
+SLC30A6	2.75E-01
+CDCA3	2.76E-01
+C17orf49	2.76E-01
+CELA3B	2.76E-01
+WNT3A	2.76E-01
+PLCXD3	2.76E-01
+CXCR5	2.76E-01
+TTBK1	2.76E-01
+SGCD	2.76E-01
+SERPINB7	2.76E-01
+KCTD11	2.76E-01
+NUP35	2.76E-01
+HMGCL	2.76E-01
+FAM9A	2.76E-01
+DEGS1	2.76E-01
+STT3A	2.76E-01
+ZDHHC8	2.77E-01
+FAM122B	2.77E-01
+TSSC1	2.77E-01
+DUSP22	2.77E-01
+SLC31A1	2.77E-01
+NUDC	2.77E-01
+ACTR5	2.77E-01
+CUL1	2.77E-01
+RNASEH2C	2.77E-01
+APTX	2.77E-01
+CYB5B	2.77E-01
+UBL3	2.77E-01
+FADS2	2.77E-01
+LHX8	2.77E-01
+CHRNA10	2.78E-01
+TBX19	2.78E-01
+TUSC5	2.78E-01
+RRAD	2.78E-01
+RFESD	2.78E-01
+OPCML	2.78E-01
+MYL1	2.78E-01
+SLC5A12	2.78E-01
+CSDC2	2.78E-01
+PRMT8	2.78E-01
+CNTNAP1	2.78E-01
+USP49	2.78E-01
+TUBA1A	2.78E-01
+B3GALNT1	2.78E-01
+BPTF	2.78E-01
+PNPLA8	2.79E-01
+CALB1	2.79E-01
+TCEA1	2.79E-01
+HTRA3	2.79E-01
+VPS26A	2.79E-01
+FARSB	2.79E-01
+CSE1L	2.79E-01
+WDFY3	2.79E-01
+SLITRK2	2.79E-01
+EDN2	2.79E-01
+ITFG1	2.79E-01
+NAP1L3	2.79E-01
+OLFM3	2.79E-01
+ATP6AP1L	2.79E-01
+TNFRSF10A	2.80E-01
+MAPK9	2.80E-01
+LRRC1	2.80E-01
+RSRC1	2.80E-01
+DEF6	2.80E-01
+PDCD6	2.80E-01
+PSMC1	2.80E-01
+MYEOV2	2.80E-01
+RAB35	2.80E-01
+CTRC	2.80E-01
+PDZRN3	2.80E-01
+IL1RAPL2	2.80E-01
+EHD4	2.80E-01
+CUX2	2.80E-01
+TEC	2.80E-01
+OR1C1	2.81E-01
+HSD11B1L	2.81E-01
+ATP5H	2.81E-01
+UPB1	2.81E-01
+RBBP6	2.81E-01
+HIST1H2BB	2.81E-01
+KLK2	2.81E-01
+CBFA2T3	2.81E-01
+RDH16	2.81E-01
+COTL1	2.81E-01
+FXYD2	2.81E-01
+PRR15L	2.81E-01
+TIMP3	2.81E-01
+PTK6	2.81E-01
+PSMA1	2.82E-01
+EIF4G3	2.82E-01
+VAPB	2.82E-01
+GTF3C1	2.82E-01
+BZW1	2.82E-01
+CKAP4	2.82E-01
+MAP7D2	2.82E-01
+CDC42	2.82E-01
+DVL3	2.82E-01
+AKAP6	2.82E-01
+ZNF292	2.82E-01
+HIST1H3B	2.82E-01
+ZNF398	2.82E-01
+PSPH	2.82E-01
+GPR61	2.82E-01
+GNGT1	2.83E-01
+KDELR2	2.83E-01
+ZBTB33	2.83E-01
+UBE4B	2.83E-01
+POP7	2.83E-01
+LHCGR	2.83E-01
+SERPINF1	2.83E-01
+SSR2	2.83E-01
+EFNA4	2.83E-01
+PSKH1	2.83E-01
+UBN2	2.83E-01
+TGFBR3	2.83E-01
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+BUD31	2.83E-01
+FAU	2.83E-01
+HEMGN	2.84E-01
+PHF10	2.84E-01
+IRAK4	2.84E-01
+TGM4	2.84E-01
+IMMP2L	2.84E-01
+ZFAND5	2.84E-01
+USP42	2.84E-01
+LST1	2.84E-01
+ATP10D	2.84E-01
+PLXNA3	2.84E-01
+RRAS2	2.84E-01
+THAP8	2.84E-01
+PPIE	2.84E-01
+CDC37L1	2.84E-01
+SCAP	2.85E-01
+MAN2A2	2.85E-01
+NAP1L5	2.85E-01
+KCTD2	2.85E-01
+RHOB	2.85E-01
+FES	2.85E-01
+NOP56	2.85E-01
+LHFPL5	2.85E-01
+MAST3	2.85E-01
+HMGN5	2.85E-01
+TLR10	2.85E-01
+AKTIP	2.85E-01
+ARF5	2.85E-01
+PFN2	2.85E-01
+SELENBP1	2.85E-01
+ETFDH	2.86E-01
+SPTLC1	2.86E-01
+REL	2.86E-01
+CCDC47	2.86E-01
+CXXC1	2.86E-01
+EIF5A	2.86E-01
+PTPN3	2.86E-01
+CUL5	2.86E-01
+EBAG9	2.86E-01
+BRSK2	2.86E-01
+KRT7	2.86E-01
+FCER1G	2.86E-01
+PTK2	2.86E-01
+RAB6A	2.86E-01
+IYD	2.87E-01
+CLN5	2.87E-01
+CAPZB	2.87E-01
+RBM5	2.87E-01
+FZD6	2.87E-01
+DNAJB5	2.87E-01
+PDDC1	2.87E-01
+C2orf78	2.87E-01
+ACAD8	2.87E-01
+TUBB6	2.87E-01
+ADAM17	2.87E-01
+DTWD2	2.87E-01
+RANBP1	2.87E-01
+CPXM2	2.87E-01
+FEZ1	2.87E-01
+TMEM71	2.88E-01
+TLR8	2.88E-01
+WNT7A	2.88E-01
+TNNI1	2.88E-01
+NRBP1	2.88E-01
+ADCY8	2.88E-01
+FOXRED1	2.88E-01
+PPM1A	2.88E-01
+FAM117A	2.88E-01
+MAP3K1	2.88E-01
+ACTL6B	2.88E-01
+PRKCQ	2.88E-01
+SNAP23	2.88E-01
+MAF1	2.88E-01
+YPEL3	2.89E-01
+TMEM150A	2.89E-01
+SEMA6D	2.89E-01
+SOSTDC1	2.89E-01
+BCL10	2.89E-01
+CLSTN1	2.89E-01
+SRP9	2.89E-01
+ASTE1	2.89E-01
+PNP	2.89E-01
+STRBP	2.89E-01
+MRP63	2.89E-01
+C1QTNF2	2.89E-01
+RDH12	2.89E-01
+E2F3	2.89E-01
+TMEM108	2.89E-01
+SNURF	2.90E-01
+CLDN8	2.90E-01
+RHOQ	2.90E-01
+SERPINB1	2.90E-01
+MLX	2.90E-01
+ASF1B	2.90E-01
+GARS	2.90E-01
+MTA3	2.90E-01
+CACNB4	2.90E-01
+GPR149	2.90E-01
+PTBP2	2.90E-01
+TBCB	2.90E-01
+B3GALT1	2.90E-01
+INPP5B	2.90E-01
+ESPL1	2.91E-01
+ZHX3	2.91E-01
+DLX4	2.91E-01
+ALG6	2.91E-01
+MRGPRX1	2.91E-01
+JAKMIP1	2.91E-01
+PFKM	2.91E-01
+DHRSX	2.91E-01
+GUCY2F	2.91E-01
+EPHA3	2.91E-01
+CELA1	2.91E-01
+KRT26	2.91E-01
+TMOD2	2.91E-01
+SLC41A1	2.91E-01
+DAPK1	2.91E-01
+CNP	2.92E-01
+RBM22	2.92E-01
+SERTAD3	2.92E-01
+KRT6C	2.92E-01
+POLR1C	2.92E-01
+SPACA1	2.92E-01
+CCM2	2.92E-01
+HOXB2	2.92E-01
+GAB2	2.92E-01
+ZC3H7B	2.92E-01
+SH3GL1	2.92E-01
+PDGFB	2.92E-01
+NAPB	2.92E-01
+ETNK1	2.92E-01
+JTB	2.93E-01
+C1orf159	2.93E-01
+TAF7	2.93E-01
+GPSM2	2.93E-01
+SLURP1	2.93E-01
+SLC23A2	2.93E-01
+WFDC6	2.93E-01
+AQP8	2.93E-01
+MRPL17	2.93E-01
+NAP1L2	2.93E-01
+ADI1	2.93E-01
+CCBL2	2.93E-01
+C9orf116	2.93E-01
+IREB2	2.93E-01
+MMAA	2.93E-01
+MATK	2.94E-01
+PGAM4	2.94E-01
+PSMB5	2.94E-01
+LPP	2.94E-01
+TUBA4A	2.94E-01
+ACADSB	2.94E-01
+SYT14	2.94E-01
+TCF4	2.94E-01
+VASH1	2.94E-01
+RFX3	2.94E-01
+TRIP6	2.94E-01
+RRS1	2.94E-01
+MKRN1	2.94E-01
+RNF26	2.94E-01
+PRKD1	2.95E-01
+KIAA1715	2.95E-01
+CLP1	2.95E-01
+MRPL11	2.95E-01
+PQLC2	2.95E-01
+PIK3R1	2.95E-01
+ABLIM2	2.95E-01
+UGT8	2.95E-01
+FUT1	2.95E-01
+UBXN10	2.95E-01
+IFLTD1	2.95E-01
+ADAT1	2.95E-01
+BTG1	2.95E-01
+OLAH	2.95E-01
+NELL1	2.95E-01
+DPY30	2.96E-01
+TPBG	2.96E-01
+COX6A2	2.96E-01
+CELF3	2.96E-01
+C9orf91	2.96E-01
+PRSS22	2.96E-01
+EGFL6	2.96E-01
+HNRNPF	2.96E-01
+KLK9	2.96E-01
+ASH2L	2.96E-01
+PRKRA	2.96E-01
+PPIA	2.96E-01
+ATG16L1	2.96E-01
+ALDOC	2.96E-01
+TMEM40	2.97E-01
+ARF3	2.97E-01
+PRSS27	2.97E-01
+UBR4	2.97E-01
+TPM2	2.97E-01
+PIGW	2.97E-01
+REXO1	2.97E-01
+RSPO4	2.97E-01
+IL22	2.97E-01
+CSNK1G2	2.97E-01
+HSP90B1	2.97E-01
+NRXN1	2.97E-01
+PRL	2.97E-01
+ARGFX	2.97E-01
+CHCHD7	2.97E-01
+CNTNAP5	2.98E-01
+PCMT1	2.98E-01
+ERAL1	2.98E-01
+URM1	2.98E-01
+PRKCA	2.98E-01
+STX1A	2.98E-01
+SLC45A3	2.98E-01
+WDR18	2.98E-01
+PLAC9	2.98E-01
+CHST5	2.98E-01
+FUT8	2.98E-01
+PEPD	2.98E-01
+PKN2	2.98E-01
+OR2G2	2.98E-01
+TMEM214	2.99E-01
+EGR1	2.99E-01
+GABARAPL1	2.99E-01
+DCBLD2	2.99E-01
+LYRM1	2.99E-01
+MRPS23	2.99E-01
+SPATA8	2.99E-01
+IVNS1ABP	2.99E-01
+HIAT1	2.99E-01
+RRAGA	2.99E-01
+LRFN2	2.99E-01
+COIL	2.99E-01
+SLC34A2	2.99E-01
+EPB42	2.99E-01
+PRPF40A	2.99E-01
+CHRNA9	3.00E-01
+TP53I11	3.00E-01
+EMP2	3.00E-01
+KCTD6	3.00E-01
+PSMG2	3.00E-01
+NMNAT1	3.00E-01
+DPH2	3.00E-01
+NDUFV3	3.00E-01
+SIM1	3.00E-01
+PPCS	3.00E-01
+CLDN10	3.00E-01
+PDXK	3.00E-01
+KDM1B	3.00E-01
+TSPO	3.00E-01
+ACAT1	3.01E-01
+TMEM87B	3.01E-01
+FBXO30	3.01E-01
+SLC6A6	3.01E-01
+ACTG2	3.01E-01
+FGGY	3.01E-01
+TCP1	3.01E-01
+TNPO3	3.01E-01
+USP32	3.01E-01
+HRH2	3.01E-01
+COX18	3.01E-01
+NUCKS1	3.01E-01
+SERPINB12	3.01E-01
+PIP4K2A	3.01E-01
+PMCH	3.01E-01
+CTSK	3.02E-01
+ACBD5	3.02E-01
+RAB4B	3.02E-01
+SEC11C	3.02E-01
+TMEM138	3.02E-01
+CBL	3.02E-01
+TM2D2	3.02E-01
+SDR9C7	3.02E-01
+SCGB3A1	3.02E-01
+ALDH1A2	3.02E-01
+CDC37	3.02E-01
+DNASE1L1	3.02E-01
+BACE2	3.02E-01
+TES	3.02E-01
+STK24	3.03E-01
+WBP1	3.03E-01
+KEAP1	3.03E-01
+SQLE	3.03E-01
+AHNAK	3.03E-01
+C1orf95	3.03E-01
+CDK4	3.03E-01
+WWTR1	3.03E-01
+ATRN	3.03E-01
+MANF	3.03E-01
+GNAT2	3.03E-01
+SRGAP3	3.03E-01
+GZMK	3.03E-01
+SH3RF1	3.03E-01
+NEU1	3.03E-01
+WWOX	3.04E-01
+MAD2L1	3.04E-01
+PLXNC1	3.04E-01
+MBD4	3.04E-01
+PTPRE	3.04E-01
+SLC2A4	3.04E-01
+ITPA	3.04E-01
+TARSL2	3.04E-01
+UBE2J2	3.04E-01
+LBX2	3.04E-01
+TMPRSS11D	3.04E-01
+KLHL2	3.04E-01
+PFKFB4	3.04E-01
+ISCU	3.04E-01
+TSPAN13	3.05E-01
+STXBP5	3.05E-01
+NAMPT	3.05E-01
+FERMT3	3.05E-01
+GLB1L3	3.05E-01
+LBH	3.05E-01
+GTF2IRD1	3.05E-01
+RC3H1	3.05E-01
+RDH5	3.05E-01
+OPN3	3.05E-01
+HTR3D	3.05E-01
+CCDC97	3.05E-01
+LRRC10	3.05E-01
+P2RY1	3.05E-01
+DRD2	3.05E-01
+EMID1	3.06E-01
+ARHGEF4	3.06E-01
+KDSR	3.06E-01
+CELA2B	3.06E-01
+THRSP	3.06E-01
+XAB2	3.06E-01
+PCGF5	3.06E-01
+NOS1	3.06E-01
+HDAC9	3.06E-01
+ST6GALNAC5	3.06E-01
+ZFAND6	3.06E-01
+TFPT	3.06E-01
+HLA-DMA	3.06E-01
+SPACA4	3.06E-01
+IDH2	3.07E-01
+KRT83	3.07E-01
+PHLDA2	3.07E-01
+TMEM33	3.07E-01
+BTG4	3.07E-01
+OIP5	3.07E-01
+STYX	3.07E-01
+C1orf56	3.07E-01
+SSR3	3.07E-01
+ACAA2	3.07E-01
+NFKB1	3.07E-01
+ITFG3	3.07E-01
+SLC25A36	3.07E-01
+HERC2	3.07E-01
+KCNG3	3.07E-01
+TRAIP	3.08E-01
+GNB2L1	3.08E-01
+SLC24A3	3.08E-01
+NEUROG1	3.08E-01
+CHRNG	3.08E-01
+DOK6	3.08E-01
+NDUFA2	3.08E-01
+MOS	3.08E-01
+TMEM14E	3.08E-01
+ZNF131	3.08E-01
+KCTD21	3.08E-01
+SLAIN2	3.08E-01
+PSRC1	3.08E-01
+AGA	3.08E-01
+IL17A	3.09E-01
+SLC35C1	3.09E-01
+ADAMTS6	3.09E-01
+RFWD2	3.09E-01
+GOSR1	3.09E-01
+NAA10	3.09E-01
+KRT28	3.09E-01
+GLRA3	3.09E-01
+RHOC	3.09E-01
+SH3KBP1	3.09E-01
+LRRC3	3.09E-01
+RNF125	3.09E-01
+AGMAT	3.09E-01
+ADAL	3.09E-01
+WASF2	3.09E-01
+FUT7	3.10E-01
+AARSD1	3.10E-01
+MXRA5	3.10E-01
+TGIF1	3.10E-01
+CLVS2	3.10E-01
+ERBB3	3.10E-01
+IL21	3.10E-01
+PRR11	3.10E-01
+ST18	3.10E-01
+ARL6	3.10E-01
+GIPC3	3.10E-01
+PRSS12	3.10E-01
+FXYD6	3.10E-01
+RUNX1T1	3.10E-01
+HPGD	3.11E-01
+PVR	3.11E-01
+ERI3	3.11E-01
+ACTR1B	3.11E-01
+CTPS2	3.11E-01
+CENPP	3.11E-01
+MRPL53	3.11E-01
+POLR2C	3.11E-01
+MTF2	3.11E-01
+MED4	3.11E-01
+DDX5	3.11E-01
+CSH2	3.11E-01
+LHFP	3.11E-01
+CRABP1	3.11E-01
+FBXL5	3.11E-01
+KIAA0195	3.12E-01
+SIK3	3.12E-01
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+COPA	3.12E-01
+ACTRT1	3.12E-01
+PPP1R2	3.12E-01
+NINJ1	3.12E-01
+ZGLP1	3.12E-01
+HADH	3.12E-01
+FRMD1	3.12E-01
+MDK	3.12E-01
+TBC1D13	3.12E-01
+CAP2	3.12E-01
+MAD2L1BP	3.13E-01
+DCC	3.13E-01
+SEC23IP	3.13E-01
+ALDH3A1	3.13E-01
+MMADHC	3.13E-01
+TKTL2	3.13E-01
+UBL4A	3.13E-01
+CTSG	3.13E-01
+COQ9	3.13E-01
+KIF2A	3.13E-01
+PIK3CB	3.13E-01
+HIP1	3.13E-01
+KRT79	3.13E-01
+PRM2	3.13E-01
+CCDC3	3.13E-01
+NDUFA9	3.14E-01
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+SLBP	3.14E-01
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+ZNF740	3.14E-01
+ZYX	3.14E-01
+PXMP4	3.14E-01
+INS-IGF2	3.14E-01
+THUMPD2	3.14E-01
+SUB1	3.14E-01
+SGCG	3.14E-01
+CCNT1	3.14E-01
+OR10H5	3.15E-01
+CORT	3.15E-01
+DNPEP	3.15E-01
+ZC3H15	3.15E-01
+ULK1	3.15E-01
+RANGAP1	3.15E-01
+AGAP1	3.15E-01
+BRF2	3.15E-01
+CNOT6	3.15E-01
+OTOF	3.15E-01
+COX7C	3.15E-01
+YBX2	3.15E-01
+NOC4L	3.15E-01
+CYB561D1	3.15E-01
+ATP5I	3.15E-01
+SLFN11	3.16E-01
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+USP3	3.16E-01
+MLF2	3.16E-01
+MAP2	3.16E-01
+PHF17	3.16E-01
+PFDN2	3.16E-01
+NXNL2	3.16E-01
+CSMD2	3.16E-01
+CNN1	3.16E-01
+TRPC1	3.16E-01
+ROCK2	3.16E-01
+GNG8	3.16E-01
+KIF5B	3.16E-01
+EIF2B2	3.17E-01
+FZD10	3.17E-01
+LTV1	3.17E-01
+LCLAT1	3.17E-01
+NFKBID	3.17E-01
+MDM2	3.17E-01
+CAMK2N2	3.17E-01
+MEGF9	3.17E-01
+CYBRD1	3.17E-01
+ATP8B1	3.17E-01
+PTPRS	3.17E-01
+WASF1	3.17E-01
+AUTS2	3.17E-01
+MARCH4	3.17E-01
+DDN	3.17E-01
+ALS2	3.18E-01
+SETMAR	3.18E-01
+METTL9	3.18E-01
+OPA3	3.18E-01
+MMACHC	3.18E-01
+RDH13	3.18E-01
+MIER3	3.18E-01
+USP19	3.18E-01
+ADAMTS15	3.18E-01
+CYTH2	3.18E-01
+NLRP8	3.18E-01
+ANKRD13D	3.18E-01
+MTCH1	3.18E-01
+BTG2	3.18E-01
+INO80C	3.18E-01
+ATOH7	3.19E-01
+CXADR	3.19E-01
+CCNY	3.19E-01
+DUSP13	3.19E-01
+IFT57	3.19E-01
+LPIN2	3.19E-01
+CSN2	3.19E-01
+ARHGAP5	3.19E-01
+LENG8	3.19E-01
+ABR	3.19E-01
+PRPF39	3.19E-01
+GPR125	3.19E-01
+DYNC1LI1	3.19E-01
+PKP4	3.19E-01
+ADAM12	3.20E-01
+FDFT1	3.20E-01
+EIF1	3.20E-01
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+COLEC10	3.20E-01
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+LANCL2	3.20E-01
+KIAA2018	3.20E-01
+DDX4	3.20E-01
+HADHB	3.20E-01
+TGM3	3.20E-01
+C3orf27	3.20E-01
+EXOSC3	3.20E-01
+BMX	3.20E-01
+GPRC5D	3.20E-01
+LGSN	3.21E-01
+EPSTI1	3.21E-01
+ABCF1	3.21E-01
+OLFML3	3.21E-01
+HIST1H3D	3.21E-01
+ANGPTL2	3.21E-01
+SCAI	3.21E-01
+ARG1	3.21E-01
+GPR22	3.21E-01
+EIF4A1	3.21E-01
+PNO1	3.21E-01
+C6orf120	3.21E-01
+CDKN2C	3.21E-01
+PMM1	3.21E-01
+COLEC11	3.22E-01
+RNF24	3.22E-01
+TMEM219	3.22E-01
+ERMN	3.22E-01
+C17orf98	3.22E-01
+FKTN	3.22E-01
+MAN2B2	3.22E-01
+GJB5	3.22E-01
+DCPS	3.22E-01
+IGJ	3.22E-01
+TPK1	3.22E-01
+GPRC5A	3.22E-01
+ATP10B	3.22E-01
+NFATC1	3.22E-01
+SPATA12	3.22E-01
+PARD6B	3.23E-01
+ERC1	3.23E-01
+F12	3.23E-01
+BSND	3.23E-01
+HIST1H3I	3.23E-01
+KDELR1	3.23E-01
+FKBP3	3.23E-01
+FAT4	3.23E-01
+PCYT1A	3.23E-01
+YIPF4	3.23E-01
+ASPHD2	3.23E-01
+GOLGA7	3.23E-01
+TSPYL6	3.23E-01
+BOLA1	3.23E-01
+AKT2	3.24E-01
+DPM3	3.24E-01
+CHRNA5	3.24E-01
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+ROBO2	3.24E-01
+MYL6	3.24E-01
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+KRTAP23-1	3.24E-01
+HAUS1	3.24E-01
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+ADAMTS5	3.24E-01
+TTYH3	3.24E-01
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+TOMM34	3.24E-01
+UBE2B	3.24E-01
+ESM1	3.25E-01
+PFDN1	3.25E-01
+LRRC20	3.25E-01
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+SIK1	3.25E-01
+PRKRIR	3.25E-01
+SVEP1	3.25E-01
+CCDC138	3.25E-01
+DOK5	3.25E-01
+GCKR	3.25E-01
+WAC	3.25E-01
+TNFAIP8L2	3.25E-01
+EHHADH	3.25E-01
+CELA2A	3.25E-01
+MTUS2	3.26E-01
+NHLRC3	3.26E-01
+DPP8	3.26E-01
+TSKS	3.26E-01
+ACCS	3.26E-01
+CCDC85A	3.26E-01
+MBD2	3.26E-01
+LAMC1	3.26E-01
+HSD17B2	3.26E-01
+ARHGAP6	3.26E-01
+BATF3	3.26E-01
+RBPMS	3.26E-01
+TMEM133	3.26E-01
+LLGL1	3.26E-01
+AADAT	3.26E-01
+PGAP2	3.27E-01
+HMGCLL1	3.27E-01
+PPP2R5D	3.27E-01
+LIMD1	3.27E-01
+KLHL10	3.27E-01
+DGKI	3.27E-01
+ACPL2	3.27E-01
+PDE4D	3.27E-01
+PXMP2	3.27E-01
+SLC6A14	3.27E-01
+ATG2A	3.27E-01
+GAS6	3.27E-01
+STX10	3.27E-01
+TMEM39A	3.27E-01
+CYP4F3	3.28E-01
+UNC13C	3.28E-01
+N4BP3	3.28E-01
+KATNA1	3.28E-01
+OPRD1	3.28E-01
+ZNF385A	3.28E-01
+CRLF1	3.28E-01
+BTF3L4	3.28E-01
+HIST1H4D	3.28E-01
+FCHO2	3.28E-01
+TANK	3.28E-01
+RAB3IP	3.28E-01
+PNLDC1	3.28E-01
+AZGP1	3.28E-01
+GNPAT	3.28E-01
+TMEM132D	3.29E-01
+CDH1	3.29E-01
+CXCR4	3.29E-01
+HDAC3	3.29E-01
+RMND5B	3.29E-01
+ETHE1	3.29E-01
+POR	3.29E-01
+PDE8A	3.29E-01
+HARBI1	3.29E-01
+MATN1	3.29E-01
+TMEM161B	3.29E-01
+LRRC42	3.29E-01
+BRD9	3.29E-01
+MPZL1	3.29E-01
+SLC25A1	3.30E-01
+DCTN6	3.30E-01
+CHSY3	3.30E-01
+PTPRF	3.30E-01
+NPL	3.30E-01
+KBTBD6	3.30E-01
+TCF23	3.30E-01
+CNNM4	3.30E-01
+TMEM203	3.30E-01
+EZH1	3.30E-01
+PRPF18	3.30E-01
+FBXO33	3.30E-01
+CFP	3.30E-01
+TOX4	3.30E-01
+BTBD10	3.30E-01
+ALDH5A1	3.31E-01
+CSRNP3	3.31E-01
+TINAG	3.31E-01
+TNFSF10	3.31E-01
+DEFB134	3.31E-01
+PPAPDC3	3.31E-01
+EIF4E2	3.31E-01
+CDR1	3.31E-01
+GNPTG	3.31E-01
+OGFOD2	3.31E-01
+LDHB	3.31E-01
+RNPS1	3.31E-01
+SEZ6L	3.31E-01
+MAP3K13	3.31E-01
+CACNB3	3.32E-01
+GPR132	3.32E-01
+TPM4	3.32E-01
+CNTNAP4	3.32E-01
+EBF2	3.32E-01
+GPR183	3.32E-01
+PCGF2	3.32E-01
+GFPT1	3.32E-01
+GAP43	3.32E-01
+TMCO5A	3.32E-01
+GABRG1	3.32E-01
+RLBP1	3.32E-01
+VPS37B	3.32E-01
+SEPT11	3.32E-01
+GRHPR	3.32E-01
+PTP4A3	3.33E-01
+ZNF689	3.33E-01
+HOXD10	3.33E-01
+CPXM1	3.33E-01
+PARS2	3.33E-01
+CHAF1B	3.33E-01
+HAT1	3.33E-01
+CITED1	3.33E-01
+MOB2	3.33E-01
+RPAP2	3.33E-01
+TAF6L	3.33E-01
+CAMK2N1	3.33E-01
+KCTD10	3.33E-01
+TMPRSS11F	3.33E-01
+PCGF3	3.34E-01
+TMEM179	3.34E-01
+NDUFB8	3.34E-01
+PWWP2A	3.34E-01
+LMBRD2	3.34E-01
+TAF11	3.34E-01
+WSCD1	3.34E-01
+E2F6	3.34E-01
+LRRC8D	3.34E-01
+KCNK13	3.34E-01
+TNFRSF9	3.34E-01
+ELAVL3	3.34E-01
+SCOC	3.34E-01
+MEAF6	3.34E-01
+CAPN12	3.34E-01
+C3	3.35E-01
+PPP1R1B	3.35E-01
+PLXNB2	3.35E-01
+SNX6	3.35E-01
+CYB5R4	3.35E-01
+CAPN7	3.35E-01
+CNPY3	3.35E-01
+SDHC	3.35E-01
+BEST4	3.35E-01
+FAIM3	3.35E-01
+PSMB6	3.35E-01
+DOCK2	3.35E-01
+ABT1	3.35E-01
+LRRC55	3.35E-01
+TMTC2	3.36E-01
+TMEM17	3.36E-01
+IP6K1	3.36E-01
+TBC1D10A	3.36E-01
+PDCD2	3.36E-01
+RAB5B	3.36E-01
+CDC123	3.36E-01
+GADD45B	3.36E-01
+ASCL3	3.36E-01
+FAM46A	3.36E-01
+SART1	3.36E-01
+MLLT10	3.36E-01
+SLC41A2	3.36E-01
+IGSF21	3.36E-01
+STRA13	3.36E-01
+MARCH3	3.37E-01
+CAPN11	3.37E-01
+HIST1H3H	3.37E-01
+FKBP10	3.37E-01
+THBS3	3.37E-01
+WDR92	3.37E-01
+PRKAG1	3.37E-01
+WNT1	3.37E-01
+KDM1A	3.37E-01
+HIST2H2BE	3.37E-01
+PELI1	3.37E-01
+MOCOS	3.37E-01
+FUT9	3.37E-01
+CBX3	3.37E-01
+PYCR2	3.38E-01
+SLC25A37	3.38E-01
+IRAK1BP1	3.38E-01
+ESCO1	3.38E-01
+ZNF202	3.38E-01
+CCR4	3.38E-01
+MAGT1	3.38E-01
+BTBD11	3.38E-01
+MMP16	3.38E-01
+FAM76A	3.38E-01
+DNM3	3.38E-01
+DHRS2	3.38E-01
+ACOXL	3.38E-01
+BCORL1	3.38E-01
+GLRA2	3.38E-01
+CSRP3	3.39E-01
+TSG101	3.39E-01
+STAT4	3.39E-01
+TRPV5	3.39E-01
+FAM196A	3.39E-01
+HIVEP1	3.39E-01
+TTK	3.39E-01
+CCS	3.39E-01
+IGF2R	3.39E-01
+FAM57B	3.39E-01
+HNRNPA1L2	3.39E-01
+AGXT2	3.39E-01
+NCOR2	3.39E-01
+GJC3	3.39E-01
+CLIC4	3.40E-01
+ADM	3.40E-01
+C9orf64	3.40E-01
+TCAP	3.40E-01
+MAGEA4	3.40E-01
+VGLL3	3.40E-01
+CTNNA1	3.40E-01
+TGFB1I1	3.40E-01
+CNGA1	3.40E-01
+DSTYK	3.40E-01
+BCL7B	3.40E-01
+KRT36	3.40E-01
+DNAJB8	3.40E-01
+STMN4	3.40E-01
+FAM172A	3.40E-01
+GADD45A	3.41E-01
+HPS6	3.41E-01
+ID1	3.41E-01
+DHTKD1	3.41E-01
+PLCXD2	3.41E-01
+RASGRP2	3.41E-01
+TMEM30A	3.41E-01
+HAPLN1	3.41E-01
+E2F8	3.41E-01
+CHL1	3.41E-01
+PHPT1	3.41E-01
+STK39	3.41E-01
+DHRS4	3.41E-01
+AKT3	3.41E-01
+HLA-DRA	3.42E-01
+ANAPC5	3.42E-01
+PRKD3	3.42E-01
+LIPH	3.42E-01
+DMD	3.42E-01
+GLRB	3.42E-01
+ETNK2	3.42E-01
+DHRS13	3.42E-01
+TMED10	3.42E-01
+KARS	3.42E-01
+MAN1C1	3.42E-01
+ADCK5	3.42E-01
+CMPK1	3.42E-01
+ZNF32	3.42E-01
+UBA1	3.42E-01
+C9orf41	3.43E-01
+NOP10	3.43E-01
+PEX19	3.43E-01
+GTF2F2	3.43E-01
+ARID1B	3.43E-01
+TSPAN4	3.43E-01
+MRPS22	3.43E-01
+KLK14	3.43E-01
+GMPPA	3.43E-01
+ING1	3.43E-01
+PTH2	3.43E-01
+HM13	3.43E-01
+MPL	3.43E-01
+PTPN4	3.43E-01
+CELF4	3.44E-01
+TMPRSS13	3.44E-01
+C5orf49	3.44E-01
+ACADL	3.44E-01
+ATP8B4	3.44E-01
+SRMS	3.44E-01
+INO80E	3.44E-01
+CINP	3.44E-01
+ACMSD	3.44E-01
+PABPC1L	3.44E-01
+UBXN4	3.44E-01
+CH25H	3.44E-01
+MKX	3.44E-01
+ZNF121	3.44E-01
+CRYAB	3.44E-01
+FAR1	3.45E-01
+RB1CC1	3.45E-01
+GLI2	3.45E-01
+ASB1	3.45E-01
+COX17	3.45E-01
+HERPUD2	3.45E-01
+C6orf223	3.45E-01
+SLC2A3	3.45E-01
+WTAP	3.45E-01
+NCLN	3.45E-01
+STEAP2	3.45E-01
+CHUK	3.45E-01
+MED12L	3.45E-01
+MRGPRF	3.45E-01
+FMR1NB	3.46E-01
+UNC119	3.46E-01
+IL5	3.46E-01
+CELA3A	3.46E-01
+PLRG1	3.46E-01
+NOL8	3.46E-01
+ZNF81	3.46E-01
+PDCL	3.46E-01
+SLC35F2	3.46E-01
+OPN5	3.46E-01
+REPS2	3.46E-01
+CMTM7	3.46E-01
+TERF2	3.46E-01
+MIER2	3.46E-01
+DMGDH	3.46E-01
+RGS7	3.47E-01
+C11orf48	3.47E-01
+SPANXN3	3.47E-01
+TRNAU1AP	3.47E-01
+SLC7A6OS	3.47E-01
+NPAS3	3.47E-01
+HADHA	3.47E-01
+CMTM6	3.47E-01
+SPDYA	3.47E-01
+KAL1	3.47E-01
+FAM120C	3.47E-01
+CCDC64	3.47E-01
+HEXIM2	3.47E-01
+FTMT	3.47E-01
+THAP1	3.48E-01
+GK2	3.48E-01
+RBM39	3.48E-01
+CSNK1E	3.48E-01
+BEST2	3.48E-01
+TBXA2R	3.48E-01
+LDHAL6B	3.48E-01
+PACRG	3.48E-01
+ATG4D	3.48E-01
+HCFC2	3.48E-01
+UBE2I	3.48E-01
+BMI1	3.48E-01
+HPR	3.48E-01
+C10orf111	3.48E-01
+MRAP	3.48E-01
+TGFBRAP1	3.49E-01
+CHMP5	3.49E-01
+HAUS7	3.49E-01
+HIVEP3	3.49E-01
+CKAP5	3.49E-01
+CDC42EP4	3.49E-01
+MED22	3.49E-01
+CPNE2	3.49E-01
+SCG2	3.49E-01
+GNAT1	3.49E-01
+PPP1R15B	3.49E-01
+CDC42EP2	3.49E-01
+C8orf58	3.49E-01
+ROCK1	3.49E-01
+TIPARP	3.50E-01
+ATF2	3.50E-01
+BRD1	3.50E-01
+TICAM1	3.50E-01
+ARHGDIB	3.50E-01
+IQSEC3	3.50E-01
+ZFYVE27	3.50E-01
+ELMOD1	3.50E-01
+ERGIC1	3.50E-01
+WBP2	3.50E-01
+PTPN12	3.50E-01
+PIKFYVE	3.50E-01
+CERCAM	3.50E-01
+UCK1	3.50E-01
+KRTAP20-2	3.50E-01
+TRPV6	3.51E-01
+CYP1B1	3.51E-01
+CNTN1	3.51E-01
+OVOL1	3.51E-01
+RIT1	3.51E-01
+CRY1	3.51E-01
+ST3GAL1	3.51E-01
+SMPDL3A	3.51E-01
+TNNC2	3.51E-01
+ZIC4	3.51E-01
+GTF3C6	3.51E-01
+MEIS1	3.51E-01
+ARID4A	3.51E-01
+STAR	3.51E-01
+CNR1	3.51E-01
+CALN1	3.52E-01
+ARID3A	3.52E-01
+CUEDC2	3.52E-01
+DPP10	3.52E-01
+TMEM41A	3.52E-01
+SAFB2	3.52E-01
+FAM96B	3.52E-01
+PHF2	3.52E-01
+SSNA1	3.52E-01
+PHF8	3.52E-01
+CHRNA2	3.52E-01
+BARX2	3.52E-01
+KCNK1	3.52E-01
+MRAP2	3.52E-01
+CHRNA6	3.53E-01
+CDH9	3.53E-01
+FAM60A	3.53E-01
+GAN	3.53E-01
+CCL19	3.53E-01
+TMEM187	3.53E-01
+GRAMD1B	3.53E-01
+LCE3A	3.53E-01
+PDCD5	3.53E-01
+PARD6A	3.53E-01
+RAB40C	3.53E-01
+GDF15	3.53E-01
+FSHB	3.53E-01
+CISH	3.53E-01
+RAB13	3.53E-01
+TIA1	3.54E-01
+SLC25A22	3.54E-01
+SLC18A2	3.54E-01
+TPH1	3.54E-01
+NCOA6	3.54E-01
+STIP1	3.54E-01
+FBXW11	3.54E-01
+ARPP21	3.54E-01
+RABIF	3.54E-01
+B3GNT7	3.54E-01
+CYB5A	3.54E-01
+TMEM56	3.54E-01
+IRS1	3.54E-01
+EPO	3.54E-01
+MYCBP	3.55E-01
+PHYHIPL	3.55E-01
+SEC24A	3.55E-01
+NAA40	3.55E-01
+NRBF2	3.55E-01
+AASS	3.55E-01
+TNRC6C	3.55E-01
+KCTD8	3.55E-01
+GIT1	3.55E-01
+NEK8	3.55E-01
+STARD5	3.55E-01
+ASAP2	3.55E-01
+MRFAP1L1	3.55E-01
+HELT	3.55E-01
+RABL5	3.55E-01
+TPRG1	3.56E-01
+COX6A1	3.56E-01
+CHEK2	3.56E-01
+HIST4H4	3.56E-01
+FGA	3.56E-01
+SLC39A8	3.56E-01
+GPD2	3.56E-01
+MTNR1B	3.56E-01
+ZCCHC12	3.56E-01
+WSB2	3.56E-01
+STOML1	3.56E-01
+B3GALT5	3.56E-01
+WARS2	3.56E-01
+DIP2C	3.56E-01
+SAMD8	3.57E-01
+ARL3	3.57E-01
+BLOC1S2	3.57E-01
+TMEM132B	3.57E-01
+LGI2	3.57E-01
+KANK2	3.57E-01
+CDH18	3.57E-01
+AKT1	3.57E-01
+TBC1D25	3.57E-01
+SREBF2	3.57E-01
+RHOH	3.57E-01
+CCDC126	3.57E-01
+URGCP	3.57E-01
+PUF60	3.57E-01
+DNAJC2	3.57E-01
+FAM171B	3.58E-01
+UCP3	3.58E-01
+GZMH	3.58E-01
+THAP11	3.58E-01
+USP5	3.58E-01
+GPC1	3.58E-01
+ATP6V0E1	3.58E-01
+CFH	3.58E-01
+CDC25A	3.58E-01
+DDX21	3.58E-01
+TMUB1	3.58E-01
+LNPEP	3.58E-01
+C17orf64	3.58E-01
+PCSK7	3.58E-01
+FOXR1	3.59E-01
+SAMD10	3.59E-01
+HEXDC	3.59E-01
+APOA2	3.59E-01
+RAE1	3.59E-01
+LPIN1	3.59E-01
+NR0B2	3.59E-01
+ELF4	3.59E-01
+KRTAP1-3	3.59E-01
+C14orf142	3.59E-01
+TPPP	3.59E-01
+SLC25A3	3.59E-01
+RPE	3.59E-01
+SHARPIN	3.59E-01
+ABCG5	3.59E-01
+EDNRB	3.60E-01
+RHOU	3.60E-01
+SAMD12	3.60E-01
+ARMC1	3.60E-01
+ARFIP2	3.60E-01
+MRPL15	3.60E-01
+L2HGDH	3.60E-01
+TEX14	3.60E-01
+SULT1C2	3.60E-01
+TPST1	3.60E-01
+HTT	3.60E-01
+IQCJ	3.60E-01
+MRPS6	3.60E-01
+NDST2	3.60E-01
+ITGB1BP1	3.61E-01
+CD27	3.61E-01
+BSX	3.61E-01
+PGS1	3.61E-01
+HHIP	3.61E-01
+PLXNA1	3.61E-01
+TPR	3.61E-01
+CCT2	3.61E-01
+ANKRD13B	3.61E-01
+ASNA1	3.61E-01
+UBE2M	3.61E-01
+DSG1	3.61E-01
+C15orf38	3.61E-01
+PEF1	3.61E-01
+ELOF1	3.61E-01
+HMGN1	3.62E-01
+C16orf45	3.62E-01
+KCTD15	3.62E-01
+PNOC	3.62E-01
+CTGF	3.62E-01
+NBEA	3.62E-01
+SIAH3	3.62E-01
+NIPAL1	3.62E-01
+ZYG11B	3.62E-01
+SLC35A1	3.62E-01
+UBAC1	3.62E-01
+SH3BGRL	3.62E-01
+SLC8A1	3.62E-01
+EVI2A	3.62E-01
+ANK2	3.63E-01
+SLC34A1	3.63E-01
+BBOX1	3.63E-01
+KCNE2	3.63E-01
+INPP5J	3.63E-01
+MAGEA6	3.63E-01
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+ASTN2	3.63E-01
+PTGER2	3.63E-01
+SSTR1	3.63E-01
+EGFL7	3.63E-01
+SCN4B	3.63E-01
+C9orf89	3.63E-01
+BRD4	3.63E-01
+PPP4R1	3.63E-01
+BAP1	3.64E-01
+CAPN13	3.64E-01
+LDLRAD1	3.64E-01
+HOXB13	3.64E-01
+RNASE1	3.64E-01
+DRAM1	3.64E-01
+PRKAB1	3.64E-01
+F2R	3.64E-01
+EIF2B1	3.64E-01
+BTBD7	3.64E-01
+GGA1	3.64E-01
+CLSTN3	3.64E-01
+BAI3	3.64E-01
+UQCRC1	3.64E-01
+ZNF282	3.65E-01
+FEM1C	3.65E-01
+ICA1L	3.65E-01
+ZPLD1	3.65E-01
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+FSTL4	3.65E-01
+ADSS	3.65E-01
+RBMS1	3.65E-01
+SPTBN4	3.65E-01
+PRRG3	3.65E-01
+FTCD	3.65E-01
+ARL6IP6	3.65E-01
+APOO	3.65E-01
+HECTD1	3.65E-01
+GJA9	3.65E-01
+CDK14	3.66E-01
+FAM45A	3.66E-01
+PAGE1	3.66E-01
+LUM	3.66E-01
+WWP2	3.66E-01
+RAPH1	3.66E-01
+HMGN3	3.66E-01
+PKD2	3.66E-01
+SMC1B	3.66E-01
+EMP1	3.66E-01
+PTPRU	3.66E-01
+MAP2K6	3.66E-01
+ST13	3.66E-01
+UBE2Q2	3.66E-01
+EEF1B2	3.67E-01
+IL23R	3.67E-01
+MUM1L1	3.67E-01
+SFTPD	3.67E-01
+SLC6A11	3.67E-01
+DGKQ	3.67E-01
+C12orf5	3.67E-01
+CLCF1	3.67E-01
+MAP1A	3.67E-01
+MYF5	3.67E-01
+KIN	3.67E-01
+FOXR2	3.67E-01
+CYB5R1	3.67E-01
+TMEM206	3.67E-01
+UBASH3B	3.67E-01
+GABRR1	3.68E-01
+NOXA1	3.68E-01
+QTRTD1	3.68E-01
+ZNF691	3.68E-01
+ZNF649	3.68E-01
+MDH2	3.68E-01
+MYO1H	3.68E-01
+ZNF750	3.68E-01
+FLI1	3.68E-01
+GREM2	3.68E-01
+TAF9	3.68E-01
+CSPG5	3.68E-01
+DTYMK	3.68E-01
+ZNF655	3.68E-01
+PPEF1	3.69E-01
+RASSF7	3.69E-01
+ARID3B	3.69E-01
+C7orf41	3.69E-01
+NUDCD3	3.69E-01
+NRIP2	3.69E-01
+GPBP1L1	3.69E-01
+GLS	3.69E-01
+OR51A2	3.69E-01
+NDUFB10	3.69E-01
+CNKSR2	3.69E-01
+RRP9	3.69E-01
+TRIM11	3.69E-01
+SMYD2	3.69E-01
+PSMD14	3.69E-01
+SHE	3.70E-01
+GALNT9	3.70E-01
+SNX2	3.70E-01
+RNF114	3.70E-01
+ADCY4	3.70E-01
+CFB	3.70E-01
+TNFRSF6B	3.70E-01
+PLEKHG3	3.70E-01
+C9orf135	3.70E-01
+UBB	3.70E-01
+PPP1R14B	3.70E-01
+CDK16	3.70E-01
+KRTDAP	3.70E-01
+PNLIPRP3	3.70E-01
+VAT1	3.71E-01
+MED27	3.71E-01
+EXOC3	3.71E-01
+C19orf73	3.71E-01
+ARHGEF11	3.71E-01
+NKG7	3.71E-01
+MC2R	3.71E-01
+HEXB	3.71E-01
+IFT20	3.71E-01
+SLC2A6	3.71E-01
+CDC16	3.71E-01
+MPRIP	3.71E-01
+GPR176	3.71E-01
+VPS37C	3.71E-01
+UQCRQ	3.71E-01
+ARHGEF15	3.72E-01
+C9	3.72E-01
+CBR1	3.72E-01
+ATAD5	3.72E-01
+KPNA2	3.72E-01
+PTRF	3.72E-01
+DNAJC13	3.72E-01
+BFSP1	3.72E-01
+PEX14	3.72E-01
+GNA14	3.72E-01
+TXNL1	3.72E-01
+CD97	3.72E-01
+UBAC2	3.72E-01
+FAM134A	3.72E-01
+CCDC134	3.73E-01
+SLC25A46	3.73E-01
+FOSB	3.73E-01
+SFN	3.73E-01
+FZD3	3.73E-01
+NAV2	3.73E-01
+NEU3	3.73E-01
+OC90	3.73E-01
+SUMO3	3.73E-01
+HSD17B6	3.73E-01
+CMTM3	3.73E-01
+LEP	3.73E-01
+NTHL1	3.73E-01
+POLR2F	3.73E-01
+TSLP	3.73E-01
+BECN1	3.74E-01
+EIF1B	3.74E-01
+STX8	3.74E-01
+ATP8A2	3.74E-01
+RNF219	3.74E-01
+SYCP3	3.74E-01
+PALM2	3.74E-01
+OLR1	3.74E-01
+CHMP6	3.74E-01
+ATXN2	3.74E-01
+NPEPPS	3.74E-01
+GUCY2C	3.74E-01
+HNRNPM	3.74E-01
+ITGAL	3.74E-01
+IL17REL	3.75E-01
+PRKCZ	3.75E-01
+PUM2	3.75E-01
+ARHGAP32	3.75E-01
+DUSP4	3.75E-01
+DUSP5	3.75E-01
+SBDS	3.75E-01
+SNCB	3.75E-01
+FSD1	3.75E-01
+FNDC3A	3.75E-01
+CD52	3.75E-01
+LHB	3.75E-01
+TINAGL1	3.75E-01
+B3GAT1	3.75E-01
+IL1RN	3.75E-01
+ZNF280B	3.76E-01
+MTAP	3.76E-01
+PDE1A	3.76E-01
+CHMP2A	3.76E-01
+MARVELD3	3.76E-01
+RABGAP1L	3.76E-01
+C6orf89	3.76E-01
+GM2A	3.76E-01
+SCYL2	3.76E-01
+GOLPH3L	3.76E-01
+TSFM	3.76E-01
+DHX37	3.76E-01
+NLRP14	3.76E-01
+GDF3	3.76E-01
+HAS3	3.77E-01
+AK1	3.77E-01
+MED28	3.77E-01
+HBE1	3.77E-01
+ZNF385D	3.77E-01
+PRPSAP2	3.77E-01
+SPRED2	3.77E-01
+LHFPL1	3.77E-01
+HOXC5	3.77E-01
+DHRS11	3.77E-01
+ZDHHC9	3.77E-01
+TNRC6B	3.77E-01
+PABPC4	3.77E-01
+DTX4	3.77E-01
+KDM3A	3.77E-01
+PLOD1	3.78E-01
+CIRBP	3.78E-01
+SPDYC	3.78E-01
+PRTN3	3.78E-01
+TBC1D22B	3.78E-01
+RBM3	3.78E-01
+ZBTB7C	3.78E-01
+C15orf26	3.78E-01
+NCAM2	3.78E-01
+FMOD	3.78E-01
+PDE10A	3.78E-01
+ARG2	3.78E-01
+SP4	3.78E-01
+AFMID	3.78E-01
+GNG7	3.79E-01
+ABLIM3	3.79E-01
+TUBG1	3.79E-01
+SSH2	3.79E-01
+USP8	3.79E-01
+RAB27B	3.79E-01
+BCL7A	3.79E-01
+RNF126	3.79E-01
+IGSF1	3.79E-01
+GNMT	3.79E-01
+SLC13A4	3.79E-01
+CAPRIN1	3.79E-01
+FAM20A	3.79E-01
+WDR45	3.79E-01
+HNRNPC	3.79E-01
+PLEKHO1	3.80E-01
+C20orf197	3.80E-01
+ARMC4	3.80E-01
+CYTH1	3.80E-01
+RGL1	3.80E-01
+TAC3	3.80E-01
+TXNL4B	3.80E-01
+DIDO1	3.80E-01
+KLC2	3.80E-01
+SNF8	3.80E-01
+RHBDL1	3.80E-01
+ATP6V1E2	3.80E-01
+PTPN1	3.80E-01
+SEH1L	3.80E-01
+ATXN7	3.81E-01
+OTUD4	3.81E-01
+NEUROG3	3.81E-01
+POLR3D	3.81E-01
+CKS2	3.81E-01
+C19orf33	3.81E-01
+MRPL36	3.81E-01
+THAP5	3.81E-01
+ZNF184	3.81E-01
+NDUFA8	3.81E-01
+TCTA	3.81E-01
+HINFP	3.81E-01
+CLDN20	3.81E-01
+FAM168B	3.81E-01
+NSMAF	3.81E-01
+RIPK4	3.82E-01
+RNF19B	3.82E-01
+MBOAT2	3.82E-01
+AP4S1	3.82E-01
+PYCRL	3.82E-01
+GABARAP	3.82E-01
+DCTPP1	3.82E-01
+ZNF687	3.82E-01
+ZDHHC17	3.82E-01
+PMS2	3.82E-01
+FAM127C	3.82E-01
+TJP1	3.82E-01
+VPS36	3.82E-01
+PDCD2L	3.82E-01
+POLG2	3.83E-01
+SGOL1	3.83E-01
+CDKN2B	3.83E-01
+GOT1	3.83E-01
+JAGN1	3.83E-01
+DPAGT1	3.83E-01
+PLEKHO2	3.83E-01
+GATM	3.83E-01
+ACN9	3.83E-01
+PVRL2	3.83E-01
+LDHC	3.83E-01
+HEY2	3.83E-01
+C1QA	3.83E-01
+YIPF2	3.83E-01
+PSMB7	3.83E-01
+PDK3	3.84E-01
+TRAPPC2L	3.84E-01
+ARPC1A	3.84E-01
+RNF38	3.84E-01
+GULP1	3.84E-01
+CCDC59	3.84E-01
+BBS7	3.84E-01
+CADPS	3.84E-01
+TMOD3	3.84E-01
+CPVL	3.84E-01
+EGFL8	3.84E-01
+SURF1	3.84E-01
+DEFB131	3.84E-01
+ALG1	3.84E-01
+C16orf93	3.84E-01
+PLAC8	3.85E-01
+RIC3	3.85E-01
+ZNF830	3.85E-01
+SMC4	3.85E-01
+CRYM	3.85E-01
+PASD1	3.85E-01
+C12orf68	3.85E-01
+ZSCAN18	3.85E-01
+API5	3.85E-01
+CELSR3	3.85E-01
+DERL2	3.85E-01
+PDSS1	3.85E-01
+S100A10	3.85E-01
+ITIH1	3.85E-01
+KLHL17	3.86E-01
+RBM7	3.86E-01
+ZNF746	3.86E-01
+CDADC1	3.86E-01
+SNTA1	3.86E-01
+EDA2R	3.86E-01
+WNT8B	3.86E-01
+MAGEB18	3.86E-01
+CDH6	3.86E-01
+CD82	3.86E-01
+GTSF1	3.86E-01
+LRRN1	3.86E-01
+SYNJ2BP	3.86E-01
+SH3PXD2A	3.86E-01
+SFMBT2	3.86E-01
+TDO2	3.87E-01
+ELMO1	3.87E-01
+EXTL2	3.87E-01
+TMEM217	3.87E-01
+SSTR2	3.87E-01
+SLC9A1	3.87E-01
+OR2AE1	3.87E-01
+GPIHBP1	3.87E-01
+GPR137C	3.87E-01
+DDOST	3.87E-01
+RIPK1	3.87E-01
+MANBAL	3.87E-01
+DDO	3.87E-01
+LRRC3B	3.87E-01
+SLC8A3	3.88E-01
+SREBF1	3.88E-01
+ZFP90	3.88E-01
+HGSNAT	3.88E-01
+PRKX	3.88E-01
+C12orf4	3.88E-01
+C11orf84	3.88E-01
+CNIH3	3.88E-01
+RIBC1	3.88E-01
+BCL2L2	3.88E-01
+C14orf183	3.88E-01
+PSMA4	3.88E-01
+MLLT4	3.88E-01
+RHO	3.88E-01
+SAP18	3.88E-01
+UBQLN3	3.89E-01
+SORT1	3.89E-01
+CHTF8	3.89E-01
+CCNL1	3.89E-01
+GJB7	3.89E-01
+WWP1	3.89E-01
+RFC5	3.89E-01
+BIRC6	3.89E-01
+EDEM1	3.89E-01
+RBBP9	3.89E-01
+ALG2	3.89E-01
+PBX4	3.89E-01
+SDC1	3.89E-01
+FBXO42	3.89E-01
+CYP51A1	3.90E-01
+RNF145	3.90E-01
+HTR3E	3.90E-01
+TAF1D	3.90E-01
+ACYP1	3.90E-01
+EIF3M	3.90E-01
+PLA2G12A	3.90E-01
+KLHL12	3.90E-01
+C11orf73	3.90E-01
+NTN4	3.90E-01
+ADAP1	3.90E-01
+RHOV	3.90E-01
+CCR2	3.90E-01
+RALBP1	3.90E-01
+ST5	3.90E-01
+EXOSC2	3.91E-01
+C11orf74	3.91E-01
+PSMD10	3.91E-01
+PACRGL	3.91E-01
+CLEC2D	3.91E-01
+LGR4	3.91E-01
+HSPA12A	3.91E-01
+MEF2C	3.91E-01
+H2AFJ	3.91E-01
+KLHL24	3.91E-01
+CD99L2	3.91E-01
+TFG	3.91E-01
+ATP8B3	3.91E-01
+C10orf76	3.91E-01
+HIST1H2BC	3.92E-01
+CPE	3.92E-01
+MAGI2	3.92E-01
+PIGH	3.92E-01
+ASPRV1	3.92E-01
+OR11A1	3.92E-01
+FTO	3.92E-01
+CHRNB1	3.92E-01
+SPATC1	3.92E-01
+MORC4	3.92E-01
+RALB	3.92E-01
+MRPL10	3.92E-01
+MRM1	3.92E-01
+MUSK	3.92E-01
+HOXB4	3.92E-01
+G2E3	3.93E-01
+OVCA2	3.93E-01
+PIGR	3.93E-01
+GPR156	3.93E-01
+S100G	3.93E-01
+FIGF	3.93E-01
+TMEM18	3.93E-01
+HSPE1	3.93E-01
+ABTB2	3.93E-01
+AHR	3.93E-01
+SV2A	3.93E-01
+FXYD1	3.93E-01
+FAM120A	3.93E-01
+CHAC1	3.93E-01
+DENND2A	3.94E-01
+PRPH	3.94E-01
+NDUFA3	3.94E-01
+CD7	3.94E-01
+FIS1	3.94E-01
+FAM126B	3.94E-01
+PDE1B	3.94E-01
+PROCR	3.94E-01
+ISOC1	3.94E-01
+LSM4	3.94E-01
+PPY	3.94E-01
+C5orf46	3.94E-01
+PSD	3.94E-01
+EDARADD	3.94E-01
+CCDC117	3.94E-01
+RASL11A	3.95E-01
+PHC1	3.95E-01
+RAB21	3.95E-01
+FEZF1	3.95E-01
+ZNF326	3.95E-01
+STAU2	3.95E-01
+FLOT2	3.95E-01
+MAD2L2	3.95E-01
+ZFP1	3.95E-01
+DENND5A	3.95E-01
+CALB2	3.95E-01
+HTATSF1	3.95E-01
+FAM136A	3.95E-01
+ARFGEF2	3.95E-01
+ADRB2	3.96E-01
+ANKS1A	3.96E-01
+LIN7B	3.96E-01
+RGN	3.96E-01
+HMGB4	3.96E-01
+CNDP2	3.96E-01
+BAG4	3.96E-01
+SSTR3	3.96E-01
+CAMTA2	3.96E-01
+S1PR3	3.96E-01
+WDR16	3.96E-01
+LGR5	3.96E-01
+FCHO1	3.96E-01
+PJA1	3.96E-01
+ACTR8	3.96E-01
+WFDC2	3.97E-01
+WBP4	3.97E-01
+PICK1	3.97E-01
+HOXB8	3.97E-01
+STAC2	3.97E-01
+MAT2B	3.97E-01
+C10orf54	3.97E-01
+DKK1	3.97E-01
+ZBTB45	3.97E-01
+ISY1	3.97E-01
+CX3CR1	3.97E-01
+HIST1H2AH	3.97E-01
+LIF	3.97E-01
+APOA1	3.97E-01
+SNX21	3.98E-01
+STAM	3.98E-01
+VPS25	3.98E-01
+ZNF653	3.98E-01
+C19orf53	3.98E-01
+TMEM139	3.98E-01
+ADAMTS1	3.98E-01
+SCPEP1	3.98E-01
+ALDH7A1	3.98E-01
+FCF1	3.98E-01
+PANK3	3.98E-01
+MRPS15	3.98E-01
+BAIAP2L2	3.98E-01
+KLF8	3.98E-01
+TUBA3C	3.98E-01
+SPAG9	3.99E-01
+JAZF1	3.99E-01
+GADD45GIP1	3.99E-01
+PKP2	3.99E-01
+C2orf43	3.99E-01
+NOL6	3.99E-01
+LAG3	3.99E-01
+OR5P3	3.99E-01
+CLDN17	3.99E-01
+PDE3A	3.99E-01
+HTRA4	3.99E-01
+LMOD2	3.99E-01
+CRTC3	3.99E-01
+EIF4H	3.99E-01
+PTGES3	4.00E-01
+FCGR3B	4.00E-01
+VTI1B	4.00E-01
+MEX3C	4.00E-01
+KIAA0922	4.00E-01
+SNX22	4.00E-01
+L3MBTL3	4.00E-01
+PCDHGB1	4.00E-01
+GPR63	4.00E-01
+ACTN1	4.00E-01
+C2orf83	4.00E-01
+YTHDC2	4.00E-01
+WNT4	4.00E-01
+PDE2A	4.00E-01
+HTR7	4.00E-01
+FITM2	4.01E-01
+C12orf74	4.01E-01
+P4HB	4.01E-01
+PLAC1L	4.01E-01
+FRY	4.01E-01
+TMEM192	4.01E-01
+GPR139	4.01E-01
+PMEPA1	4.01E-01
+TMEM213	4.01E-01
+KLK1	4.01E-01
+MFSD4	4.01E-01
+UBR3	4.01E-01
+CALCRL	4.01E-01
+CPPED1	4.01E-01
+HIST2H2AC	4.02E-01
+SWAP70	4.02E-01
+PPP2R2A	4.02E-01
+MPV17	4.02E-01
+RNF111	4.02E-01
+PRLH	4.02E-01
+NUMA1	4.02E-01
+TMEM9	4.02E-01
+CD300E	4.02E-01
+ZC3H12C	4.02E-01
+YEATS2	4.02E-01
+RNF146	4.02E-01
+IQGAP1	4.02E-01
+FAM19A3	4.02E-01
+TEX12	4.02E-01
+MRPS10	4.03E-01
+TAB3	4.03E-01
+SLC43A2	4.03E-01
+CD72	4.03E-01
+APBB1IP	4.03E-01
+SLC22A5	4.03E-01
+PDE12	4.03E-01
+BLK	4.03E-01
+TMEM97	4.03E-01
+GRPR	4.03E-01
+SPIC	4.03E-01
+NICN1	4.03E-01
+FKBP9	4.03E-01
+ZBTB37	4.03E-01
+LPCAT3	4.04E-01
+STRN	4.04E-01
+BACE1	4.04E-01
+BCL6B	4.04E-01
+LTB	4.04E-01
+CD300LD	4.04E-01
+CYP4F2	4.04E-01
+NDUFAF3	4.04E-01
+TMEM198	4.04E-01
+CLDND2	4.04E-01
+CDCA4	4.04E-01
+POLR1A	4.04E-01
+PDE4B	4.04E-01
+MINK1	4.04E-01
+TMPRSS11B	4.04E-01
+LIX1L	4.05E-01
+TARS2	4.05E-01
+ILF2	4.05E-01
+PACSIN2	4.05E-01
+POP4	4.05E-01
+ALDH9A1	4.05E-01
+CD9	4.05E-01
+RICTOR	4.05E-01
+ARRB1	4.05E-01
+NDUFS3	4.05E-01
+MPDU1	4.05E-01
+ERO1L	4.05E-01
+LAMA4	4.05E-01
+LRRC59	4.05E-01
+SOCS2	4.06E-01
+ANGEL2	4.06E-01
+ENKUR	4.06E-01
+TAAR6	4.06E-01
+FBLN7	4.06E-01
+VPS35	4.06E-01
+ARL6IP5	4.06E-01
+HRSP12	4.06E-01
+DARS2	4.06E-01
+PRRG2	4.06E-01
+ATCAY	4.06E-01
+PFDN4	4.06E-01
+HYOU1	4.06E-01
+TMEM86A	4.06E-01
+HFE	4.06E-01
+PLEKHG2	4.07E-01
+ANKHD1	4.07E-01
+HIGD2A	4.07E-01
+TMEM55A	4.07E-01
+ST8SIA4	4.07E-01
+CCDC137	4.07E-01
+ZC3H13	4.07E-01
+VPS18	4.07E-01
+PHF20	4.07E-01
+HSPA4	4.07E-01
+C4orf46	4.07E-01
+CUX1	4.07E-01
+BAI2	4.07E-01
+SRGN	4.07E-01
+NIPAL2	4.08E-01
+ATPIF1	4.08E-01
+PGD	4.08E-01
+INSL6	4.08E-01
+CNOT3	4.08E-01
+ARL8B	4.08E-01
+FAM53C	4.08E-01
+UPP2	4.08E-01
+ZMYM4	4.08E-01
+CYB5RL	4.08E-01
+GALNT1	4.08E-01
+SMYD1	4.08E-01
+LASP1	4.08E-01
+ERCC2	4.08E-01
+IFITM5	4.08E-01
+NUAK1	4.09E-01
+MARCKSL1	4.09E-01
+HDC	4.09E-01
+C13orf35	4.09E-01
+BRSK1	4.09E-01
+ARHGEF18	4.09E-01
+TMEM52	4.09E-01
+METTL1	4.09E-01
+SLC35E4	4.09E-01
+PRICKLE4	4.09E-01
+MAN1B1	4.09E-01
+HERC4	4.09E-01
+SLC30A2	4.09E-01
+C1QTNF6	4.09E-01
+SEC61G	4.10E-01
+C7orf49	4.10E-01
+TNKS	4.10E-01
+INTS7	4.10E-01
+RCBTB2	4.10E-01
+ALG14	4.10E-01
+C11orf54	4.10E-01
+SUZ12	4.10E-01
+TFEC	4.10E-01
+INTS4	4.10E-01
+BIRC2	4.10E-01
+ABCG1	4.10E-01
+WNT5B	4.10E-01
+KLHL9	4.10E-01
+YWHAZ	4.10E-01
+GINS4	4.11E-01
+OSBPL9	4.11E-01
+PRDM5	4.11E-01
+CDKN2AIPNL	4.11E-01
+BEND6	4.11E-01
+TDRD1	4.11E-01
+RASL10B	4.11E-01
+CD19	4.11E-01
+ZP2	4.11E-01
+TBC1D14	4.11E-01
+FSHR	4.11E-01
+THAP6	4.11E-01
+PPP2R1A	4.11E-01
+NIPSNAP1	4.11E-01
+GALNT11	4.12E-01
+NAPA	4.12E-01
+RAD23B	4.12E-01
+MED23	4.12E-01
+RNFT2	4.12E-01
+CHST12	4.12E-01
+SEPSECS	4.12E-01
+FNDC7	4.12E-01
+DNAJC30	4.12E-01
+ZSWIM4	4.12E-01
+RBBP4	4.12E-01
+CCDC151	4.12E-01
+ARHGEF17	4.12E-01
+UBE2E3	4.12E-01
+ARL4D	4.12E-01
+CKLF	4.13E-01
+SYT13	4.13E-01
+KCTD14	4.13E-01
+INCENP	4.13E-01
+LSAMP	4.13E-01
+SMG7	4.13E-01
+B4GALT7	4.13E-01
+SRRM1	4.13E-01
+SEPT5	4.13E-01
+C10orf107	4.13E-01
+SH2D1A	4.13E-01
+ZNF462	4.13E-01
+UBLCP1	4.13E-01
+ANKIB1	4.13E-01
+NGFRAP1	4.14E-01
+USP26	4.14E-01
+WDR91	4.14E-01
+ZNF70	4.14E-01
+PTPN18	4.14E-01
+LRRC32	4.14E-01
+PTGFR	4.14E-01
+ELOVL1	4.14E-01
+MINPP1	4.14E-01
+SDC2	4.14E-01
+ZFYVE21	4.14E-01
+KDM4D	4.14E-01
+GLTP	4.14E-01
+EFHD2	4.14E-01
+GCLM	4.14E-01
+PHC2	4.15E-01
+C11orf70	4.15E-01
+MED29	4.15E-01
+UBXN1	4.15E-01
+IL12RB1	4.15E-01
+TGM7	4.15E-01
+MRPL14	4.15E-01
+C10orf53	4.15E-01
+GZMB	4.15E-01
+ENDOU	4.15E-01
+KALRN	4.15E-01
+TIGIT	4.15E-01
+KCNMB2	4.15E-01
+C11orf85	4.15E-01
+ERP44	4.16E-01
+HTRA2	4.16E-01
+SETD3	4.16E-01
+IFT81	4.16E-01
+HTR3B	4.16E-01
+IAPP	4.16E-01
+BCHE	4.16E-01
+CALML5	4.16E-01
+C15orf52	4.16E-01
+CUL3	4.16E-01
+ITGA1	4.16E-01
+TRIM36	4.16E-01
+SDF2	4.16E-01
+RAD21	4.16E-01
+GIP	4.16E-01
+GPC6	4.17E-01
+PTPRG	4.17E-01
+COBL	4.17E-01
+UBE2N	4.17E-01
+DYRK1B	4.17E-01
+MAGEA3	4.17E-01
+PDE4C	4.17E-01
+FGD3	4.17E-01
+LARGE	4.17E-01
+SLC9A5	4.17E-01
+ACBD7	4.17E-01
+KLHL1	4.17E-01
+SLC16A10	4.17E-01
+MRPL19	4.17E-01
+ZFP36L1	4.17E-01
+CPNE4	4.18E-01
+RIMBP2	4.18E-01
+N4BP2L2	4.18E-01
+SSBP1	4.18E-01
+GAS7	4.18E-01
+DEFA4	4.18E-01
+UBA5	4.18E-01
+CCNB3	4.18E-01
+PCBP3	4.18E-01
+WDR61	4.18E-01
+IL34	4.18E-01
+OR8B4	4.18E-01
+NGB	4.18E-01
+MKRN2	4.18E-01
+FBXO24	4.19E-01
+RIPPLY2	4.19E-01
+POP5	4.19E-01
+HSPD1	4.19E-01
+TECTB	4.19E-01
+EML1	4.19E-01
+ALLC	4.19E-01
+FGF11	4.19E-01
+CELF1	4.19E-01
+EID1	4.19E-01
+CNOT8	4.19E-01
+HDX	4.19E-01
+ELOVL6	4.19E-01
+ABHD2	4.19E-01
+CENPM	4.19E-01
+ALG12	4.20E-01
+RSPO2	4.20E-01
+MTCP1	4.20E-01
+ELP3	4.20E-01
+EID2B	4.20E-01
+TUBB1	4.20E-01
+RAB3GAP2	4.20E-01
+ZFP64	4.20E-01
+NDFIP2	4.20E-01
+TMEFF2	4.20E-01
+CSTF2T	4.20E-01
+STAC3	4.20E-01
+SH3BP1	4.20E-01
+CCDC127	4.20E-01
+AGRN	4.21E-01
+HIST1H1E	4.21E-01
+ZFHX4	4.21E-01
+ASAH1	4.21E-01
+EPHA8	4.21E-01
+SMPX	4.21E-01
+TIAM1	4.21E-01
+TNFAIP8	4.21E-01
+PTPRM	4.21E-01
+E2F5	4.21E-01
+CLPTM1L	4.21E-01
+TGIF2	4.21E-01
+KRTAP17-1	4.21E-01
+ERGIC2	4.21E-01
+MRPL20	4.21E-01
+TMEM95	4.22E-01
+PDE4A	4.22E-01
+NPC2	4.22E-01
+TRPM5	4.22E-01
+PGGT1B	4.22E-01
+STARD7	4.22E-01
+SGIP1	4.22E-01
+CXCL14	4.22E-01
+SPAG7	4.22E-01
+ST3GAL4	4.22E-01
+DEFB114	4.22E-01
+DNAJC11	4.22E-01
+CALU	4.22E-01
+ITLN1	4.22E-01
+LY6H	4.23E-01
+TMEM88	4.23E-01
+FUBP3	4.23E-01
+CD164	4.23E-01
+DEF8	4.23E-01
+MRPL32	4.23E-01
+RBMXL1	4.23E-01
+ARL2	4.23E-01
+RSPO1	4.23E-01
+HSPA9	4.23E-01
+PAQR8	4.23E-01
+SPTY2D1	4.23E-01
+TEX9	4.23E-01
+BAIAP2	4.23E-01
+LDHAL6A	4.23E-01
+CRELD1	4.24E-01
+IMPA2	4.24E-01
+DLG4	4.24E-01
+PLXNA2	4.24E-01
+GPATCH8	4.24E-01
+CYTH3	4.24E-01
+RUSC1	4.24E-01
+MRPS14	4.24E-01
+B4GALT6	4.24E-01
+EXOSC1	4.24E-01
+SLC25A33	4.24E-01
+MRPL24	4.24E-01
+ZNF664	4.24E-01
+PPM1B	4.24E-01
+TRIM44	4.25E-01
+TNMD	4.25E-01
+TSN	4.25E-01
+SLC1A3	4.25E-01
+MOGAT2	4.25E-01
+HIST1H2BM	4.25E-01
+WARS	4.25E-01
+FXR1	4.25E-01
+MFAP3	4.25E-01
+SHROOM3	4.25E-01
+CCL3	4.25E-01
+GRPEL2	4.25E-01
+MBL2	4.25E-01
+DCD	4.25E-01
+CDK8	4.25E-01
+METTL7B	4.26E-01
+HDAC5	4.26E-01
+TOMM20	4.26E-01
+KLHL34	4.26E-01
+OR8D2	4.26E-01
+STRA8	4.26E-01
+TMEM182	4.26E-01
+VDAC2	4.26E-01
+HEY1	4.26E-01
+AVPR1B	4.26E-01
+TUBB2A	4.26E-01
+ARHGAP11A	4.26E-01
+TRIM10	4.26E-01
+OSTF1	4.26E-01
+C1orf35	4.27E-01
+FUK	4.27E-01
+MIS12	4.27E-01
+PRDX2	4.27E-01
+ECM1	4.27E-01
+PRSS45	4.27E-01
+PRSS37	4.27E-01
+NHP2L1	4.27E-01
+ADK	4.27E-01
+POLR3F	4.27E-01
+RNF31	4.27E-01
+PNPT1	4.27E-01
+PDE7B	4.27E-01
+DCLK1	4.27E-01
+MLXIPL	4.27E-01
+C14orf79	4.28E-01
+EIF2S2	4.28E-01
+TMEM123	4.28E-01
+ACO2	4.28E-01
+PTPRR	4.28E-01
+CYP39A1	4.28E-01
+GCHFR	4.28E-01
+CCL25	4.28E-01
+ICOS	4.28E-01
+ZNF449	4.28E-01
+PDE7A	4.28E-01
+SLC25A42	4.28E-01
+RIC8A	4.28E-01
+PIPOX	4.28E-01
+C6orf48	4.29E-01
+ATP11B	4.29E-01
+KIAA1522	4.29E-01
+HSPB9	4.29E-01
+C12orf23	4.29E-01
+MLST8	4.29E-01
+TRAF4	4.29E-01
+SLC22A23	4.29E-01
+ERAS	4.29E-01
+MCM2	4.29E-01
+SNAPC1	4.29E-01
+LUZP1	4.29E-01
+STX3	4.29E-01
+GHSR	4.29E-01
+DLD	4.29E-01
+TEX19	4.30E-01
+CYB561D2	4.30E-01
+DVL1	4.30E-01
+GPT	4.30E-01
+CDX4	4.30E-01
+C11orf45	4.30E-01
+SGK1	4.30E-01
+EMR1	4.30E-01
+C10orf32	4.30E-01
+ATP6V1G1	4.30E-01
+FBXO3	4.30E-01
+FAM160A2	4.30E-01
+TSEN34	4.30E-01
+CGB1	4.30E-01
+GNAT3	4.31E-01
+ZNF581	4.31E-01
+FCRLB	4.31E-01
+TOMM40L	4.31E-01
+C8B	4.31E-01
+PRDM14	4.31E-01
+GTF2H3	4.31E-01
+DIRAS2	4.31E-01
+LPIN3	4.31E-01
+CSRNP2	4.31E-01
+ASB13	4.31E-01
+KRTAP19-1	4.31E-01
+MORN4	4.31E-01
+FNIP1	4.31E-01
+SERPINI2	4.31E-01
+GC	4.32E-01
+DIRC2	4.32E-01
+RALGPS1	4.32E-01
+FAHD2A	4.32E-01
+CCL16	4.32E-01
+OR9I1	4.32E-01
+GALNT13	4.32E-01
+HOXD12	4.32E-01
+SLC2A12	4.32E-01
+SDHA	4.32E-01
+C3orf79	4.32E-01
+MTCH2	4.32E-01
+CBFA2T2	4.32E-01
+SRP14	4.32E-01
+SP7	4.33E-01
+SDK1	4.33E-01
+ZBTB17	4.33E-01
+OTUD7B	4.33E-01
+COX6B1	4.33E-01
+C8orf76	4.33E-01
+MED25	4.33E-01
+C16orf13	4.33E-01
+GABRP	4.33E-01
+SLC2A9	4.33E-01
+UNC5D	4.33E-01
+ALCAM	4.33E-01
+DHRS7B	4.33E-01
+HIF1A	4.33E-01
+NUPR1	4.33E-01
+PRKACB	4.34E-01
+EAF2	4.34E-01
+EIF3L	4.34E-01
+CLLU1OS	4.34E-01
+TAGLN2	4.34E-01
+KCTD5	4.34E-01
+MAEA	4.34E-01
+FCN1	4.34E-01
+C9orf37	4.34E-01
+C1QTNF3	4.34E-01
+CDC34	4.34E-01
+TRIM21	4.34E-01
+RNASEH1	4.34E-01
+CABP2	4.34E-01
+AP1B1	4.35E-01
+LAPTM4A	4.35E-01
+EIF3F	4.35E-01
+RGS10	4.35E-01
+RRAS	4.35E-01
+ODF1	4.35E-01
+DGKE	4.35E-01
+B3GNT1	4.35E-01
+CCIN	4.35E-01
+MPEG1	4.35E-01
+B3GNT3	4.35E-01
+TTBK2	4.35E-01
+ZBTB9	4.35E-01
+SET	4.35E-01
+RAB4A	4.35E-01
+SGMS1	4.36E-01
+HUNK	4.36E-01
+C16orf86	4.36E-01
+C5orf48	4.36E-01
+CRTAC1	4.36E-01
+FAM49A	4.36E-01
+ATG12	4.36E-01
+BAMBI	4.36E-01
+CCDC115	4.36E-01
+CD59	4.36E-01
+WNT8A	4.36E-01
+MARK2	4.36E-01
+SFTA2	4.36E-01
+NFAM1	4.36E-01
+RHAG	4.37E-01
+IFITM2	4.37E-01
+TMEM2	4.37E-01
+SEC11A	4.37E-01
+DPH5	4.37E-01
+NIT2	4.37E-01
+TRIM26	4.37E-01
+DCP2	4.37E-01
+CNN3	4.37E-01
+PCDHGA5	4.37E-01
+HOPX	4.37E-01
+LIMD2	4.37E-01
+DBF4	4.37E-01
+TMEM5	4.37E-01
+GPATCH4	4.37E-01
+PSME3	4.38E-01
+AP1S3	4.38E-01
+PTPN21	4.38E-01
+YIF1B	4.38E-01
+TRDMT1	4.38E-01
+DNAJB4	4.38E-01
+STX11	4.38E-01
+ZNF324	4.38E-01
+HAMP	4.38E-01
+NAA15	4.38E-01
+LRRTM4	4.38E-01
+GOLGA2	4.38E-01
+C10orf35	4.38E-01
+KIF1A	4.38E-01
+TXNDC8	4.39E-01
+HIST1H4I	4.39E-01
+RBM46	4.39E-01
+GTF2A1L	4.39E-01
+TMEM26	4.39E-01
+WDR36	4.39E-01
+GPR3	4.39E-01
+FAM96A	4.39E-01
+ZNF638	4.39E-01
+NFAT5	4.39E-01
+C3orf70	4.39E-01
+TMEM62	4.39E-01
+CLEC14A	4.39E-01
+DDX24	4.39E-01
+MED20	4.39E-01
+UPF3B	4.40E-01
+LEMD3	4.40E-01
+PVRL4	4.40E-01
+STOM	4.40E-01
+ADAMTS19	4.40E-01
+FRS3	4.40E-01
+ATP5S	4.40E-01
+DHRS12	4.40E-01
+SERAC1	4.40E-01
+CD8A	4.40E-01
+EPHA6	4.40E-01
+PKP1	4.40E-01
+SCGB2A2	4.40E-01
+KCNIP1	4.40E-01
+CXCL5	4.41E-01
+IFIT5	4.41E-01
+DHX36	4.41E-01
+USP12	4.41E-01
+PLXNB3	4.41E-01
+CENPL	4.41E-01
+AQP10	4.41E-01
+CCNE1	4.41E-01
+ATAD3C	4.41E-01
+PRTFDC1	4.41E-01
+KHDRBS3	4.41E-01
+MED6	4.41E-01
+KPTN	4.41E-01
+AFF3	4.41E-01
+ITGAX	4.41E-01
+IL6ST	4.42E-01
+EPN1	4.42E-01
+KLHL38	4.42E-01
+MET	4.42E-01
+PDZK1IP1	4.42E-01
+POLR2I	4.42E-01
+CCL21	4.42E-01
+PLEKHB2	4.42E-01
+ZP1	4.42E-01
+FBXO9	4.42E-01
+TK1	4.42E-01
+PTS	4.42E-01
+CYP4F12	4.42E-01
+WDR77	4.42E-01
+ZMYND10	4.43E-01
+DEXI	4.43E-01
+NPY5R	4.43E-01
+NETO1	4.43E-01
+SNRPB	4.43E-01
+NINJ2	4.43E-01
+KLHL20	4.43E-01
+LMAN1	4.43E-01
+SEC24D	4.43E-01
+PCDHGC3	4.43E-01
+TUBA3D	4.43E-01
+DPM1	4.43E-01
+WLS	4.43E-01
+EGLN2	4.43E-01
+DUSP26	4.43E-01
+PRR23B	4.44E-01
+ARHGEF7	4.44E-01
+PACS2	4.44E-01
+ARFGEF1	4.44E-01
+PHIP	4.44E-01
+TCEA2	4.44E-01
+ARID4B	4.44E-01
+WDR83	4.44E-01
+BEND2	4.44E-01
+AKAP11	4.44E-01
+GIT2	4.44E-01
+PEA15	4.44E-01
+C9orf153	4.44E-01
+C5orf38	4.44E-01
+HIST1H3J	4.45E-01
+STXBP5L	4.45E-01
+HGS	4.45E-01
+C17orf80	4.45E-01
+CRYBB2	4.45E-01
+P2RY4	4.45E-01
+ZEB1	4.45E-01
+ARMCX3	4.45E-01
+DDX23	4.45E-01
+UTP18	4.45E-01
+ARL5A	4.45E-01
+C1orf100	4.45E-01
+BZRAP1	4.45E-01
+PRKCSH	4.45E-01
+TMEM186	4.45E-01
+GIGYF2	4.46E-01
+RIN3	4.46E-01
+ZFP82	4.46E-01
+C10orf99	4.46E-01
+ZCCHC10	4.46E-01
+TICAM2	4.46E-01
+RALGAPA2	4.46E-01
+N4BP2L1	4.46E-01
+KLF10	4.46E-01
+DYNLT3	4.46E-01
+SHROOM2	4.46E-01
+EBPL	4.46E-01
+MAGEA1	4.46E-01
+FAM133A	4.46E-01
+DPF3	4.47E-01
+CCT7	4.47E-01
+ADAMTS4	4.47E-01
+IDI1	4.47E-01
+TXNL4A	4.47E-01
+MTHFD2	4.47E-01
+AGGF1	4.47E-01
+C2orf50	4.47E-01
+CCL1	4.47E-01
+PRR22	4.47E-01
+POFUT1	4.47E-01
+TPRG1L	4.47E-01
+RBM24	4.47E-01
+AASDHPPT	4.47E-01
+COL20A1	4.47E-01
+TAF4B	4.48E-01
+C8orf37	4.48E-01
+CTSH	4.48E-01
+FAM81A	4.48E-01
+NTF3	4.48E-01
+UBE2J1	4.48E-01
+EIF3K	4.48E-01
+MID1	4.48E-01
+PFKFB1	4.48E-01
+ABHD6	4.48E-01
+MTPAP	4.48E-01
+IRGQ	4.48E-01
+SUPT4H1	4.48E-01
+OLA1	4.48E-01
+GOLT1B	4.49E-01
+GNAI3	4.49E-01
+TTC18	4.49E-01
+RAB3D	4.49E-01
+SAE1	4.49E-01
+HDAC1	4.49E-01
+PLEKHM2	4.49E-01
+PYCR1	4.49E-01
+MYL6B	4.49E-01
+SLC24A2	4.49E-01
+XCR1	4.49E-01
+STARD3NL	4.49E-01
+PRM1	4.49E-01
+ST7	4.49E-01
+DUSP11	4.49E-01
+RD3	4.50E-01
+CCDC71	4.50E-01
+CCDC142	4.50E-01
+S100A12	4.50E-01
+PDPR	4.50E-01
+GRHL3	4.50E-01
+C4orf3	4.50E-01
+HBS1L	4.50E-01
+YIPF3	4.50E-01
+PSME4	4.50E-01
+UNC93A	4.50E-01
+SPRR1B	4.50E-01
+C2ORF15	4.50E-01
+GABRQ	4.50E-01
+ADAMTS3	4.50E-01
+ZP4	4.51E-01
+PUS10	4.51E-01
+PPP1CA	4.51E-01
+APBA2	4.51E-01
+LSM5	4.51E-01
+MT1B	4.51E-01
+YBX1	4.51E-01
+GINS2	4.51E-01
+CCND3	4.51E-01
+MPP5	4.51E-01
+GK5	4.51E-01
+YES1	4.51E-01
+GRAP2	4.51E-01
+RASD1	4.51E-01
+EPT1	4.52E-01
+ZNF618	4.52E-01
+TSPYL2	4.52E-01
+HMHA1	4.52E-01
+C1orf172	4.52E-01
+SRR	4.52E-01
+SIRPA	4.52E-01
+CARTPT	4.52E-01
+SS18L1	4.52E-01
+BLOC1S1	4.52E-01
+ADAM19	4.52E-01
+IGF2BP2	4.52E-01
+ARHGAP26	4.52E-01
+NKAIN1	4.52E-01
+SLC2A5	4.52E-01
+ZC3H12A	4.53E-01
+GRHL1	4.53E-01
+RAB22A	4.53E-01
+NEK9	4.53E-01
+PLEK	4.53E-01
+HHLA3	4.53E-01
+MT1E	4.53E-01
+NAF1	4.53E-01
+TMCC1	4.53E-01
+PCP4L1	4.53E-01
+LNP1	4.53E-01
+DDX59	4.53E-01
+RBM12B	4.53E-01
+KRTAP21-2	4.53E-01
+CA10	4.54E-01
+METTL3	4.54E-01
+GMPR2	4.54E-01
+CHN2	4.54E-01
+LYZL4	4.54E-01
+ZFYVE1	4.54E-01
+ABCG2	4.54E-01
+TIAF1	4.54E-01
+SFRP2	4.54E-01
+ARMC5	4.54E-01
+OR10G4	4.54E-01
+CASP10	4.54E-01
+MARCH2	4.54E-01
+LEPROTL1	4.54E-01
+OR8B12	4.54E-01
+OR10G8	4.55E-01
+GORASP2	4.55E-01
+PPDPF	4.55E-01
+CYP17A1	4.55E-01
+PCDH11X	4.55E-01
+RANBP6	4.55E-01
+PFN4	4.55E-01
+NKAIN3	4.55E-01
+CYP4B1	4.55E-01
+NUDT17	4.55E-01
+ANP32A	4.55E-01
+CHORDC1	4.55E-01
+MLKL	4.55E-01
+PIK3C2B	4.55E-01
+HSD17B14	4.56E-01
+HOXA6	4.56E-01
+HIST1H1D	4.56E-01
+HOXA7	4.56E-01
+APAF1	4.56E-01
+DTX1	4.56E-01
+TSPAN12	4.56E-01
+TCOF1	4.56E-01
+SPARCL1	4.56E-01
+GCLC	4.56E-01
+OTOL1	4.56E-01
+CYP27B1	4.56E-01
+DARS	4.56E-01
+PSMD7	4.56E-01
+PWP2	4.56E-01
+RNF40	4.57E-01
+ZBTB5	4.57E-01
+PEMT	4.57E-01
+CKB	4.57E-01
+RCOR2	4.57E-01
+CSNK1G1	4.57E-01
+RCOR3	4.57E-01
+DIP2A	4.57E-01
+PECR	4.57E-01
+HINT3	4.57E-01
+CHMP1B	4.57E-01
+PDE5A	4.57E-01
+LYG2	4.57E-01
+ZNF436	4.57E-01
+FRK	4.58E-01
+PDCD1	4.58E-01
+WIF1	4.58E-01
+SLC16A9	4.58E-01
+RAB3B	4.58E-01
+SAR1B	4.58E-01
+MRPS25	4.58E-01
+KIF3B	4.58E-01
+MACF1	4.58E-01
+BAG2	4.58E-01
+STARD10	4.58E-01
+ADAM9	4.58E-01
+RAB23	4.58E-01
+TMOD4	4.58E-01
+KAT2B	4.58E-01
+POMGNT1	4.59E-01
+BICC1	4.59E-01
+WNT9B	4.59E-01
+CTNNBIP1	4.59E-01
+RGP1	4.59E-01
+CSNK1G3	4.59E-01
+MAPK3	4.59E-01
+ORMDL1	4.59E-01
+ZBTB22	4.59E-01
+FBXW4	4.59E-01
+OR4C12	4.59E-01
+GPR34	4.59E-01
+ENOPH1	4.59E-01
+PGM5	4.59E-01
+SNX17	4.60E-01
+USP37	4.60E-01
+ZNF821	4.60E-01
+FBP1	4.60E-01
+ZNF34	4.60E-01
+KCTD17	4.60E-01
+FBXL19	4.60E-01
+TMEM136	4.60E-01
+TSHB	4.60E-01
+SLC38A2	4.60E-01
+OR2A25	4.60E-01
+C1QTNF9	4.60E-01
+GPR171	4.60E-01
+ZNF804A	4.60E-01
+CIDEA	4.60E-01
+SAP30BP	4.61E-01
+GPR68	4.61E-01
+PRPF6	4.61E-01
+TMEM183A	4.61E-01
+GPR31	4.61E-01
+TLL1	4.61E-01
+GDF9	4.61E-01
+KIAA0247	4.61E-01
+BCL2A1	4.61E-01
+NLRP10	4.61E-01
+KIAA1211	4.61E-01
+HDLBP	4.61E-01
+MFSD9	4.61E-01
+UGDH	4.61E-01
+NGEF	4.62E-01
+LDLRAD2	4.62E-01
+GOLGA3	4.62E-01
+MDP1	4.62E-01
+BDKRB2	4.62E-01
+BRWD1	4.62E-01
+YIPF1	4.62E-01
+REEP6	4.62E-01
+RCBTB1	4.62E-01
+TERF2IP	4.62E-01
+RAB43	4.62E-01
+REPS1	4.62E-01
+FBP2	4.62E-01
+CYP26B1	4.62E-01
+LPPR4	4.62E-01
+RNF139	4.63E-01
+GPR64	4.63E-01
+SYT6	4.63E-01
+DDX19A	4.63E-01
+GUCY1B3	4.63E-01
+ZNF174	4.63E-01
+FLT1	4.63E-01
+EFHD1	4.63E-01
+SLC25A43	4.63E-01
+ZBTB41	4.63E-01
+DHRS7	4.63E-01
+HSPA2	4.63E-01
+ADAMTS16	4.63E-01
+RWDD2B	4.63E-01
+ZNF365	4.64E-01
+FGD2	4.64E-01
+CTDSP2	4.64E-01
+ACIN1	4.64E-01
+RSPO3	4.64E-01
+SRPX2	4.64E-01
+MED21	4.64E-01
+MFSD2B	4.64E-01
+LACTB	4.64E-01
+PGLYRP1	4.64E-01
+ZNF22	4.64E-01
+ARHGAP21	4.64E-01
+RAD23A	4.64E-01
+APOC2	4.64E-01
+SPI1	4.64E-01
+FYTTD1	4.65E-01
+OR2A2	4.65E-01
+DUPD1	4.65E-01
+PRELP	4.65E-01
+ZFP42	4.65E-01
+ZNRF4	4.65E-01
+ZBTB32	4.65E-01
+RANGRF	4.65E-01
+CRYGC	4.65E-01
+MRPL12	4.65E-01
+FLVCR1	4.65E-01
+YEATS4	4.65E-01
+DPP9	4.65E-01
+BMP5	4.65E-01
+STYK1	4.66E-01
+MYF6	4.66E-01
+C7orf43	4.66E-01
+PTPN7	4.66E-01
+CAMK2G	4.66E-01
+CTSF	4.66E-01
+WDR24	4.66E-01
+PRCP	4.66E-01
+PRSS8	4.66E-01
+CA2	4.66E-01
+C11orf63	4.66E-01
+KIAA0513	4.66E-01
+LSM14B	4.66E-01
+DOK2	4.66E-01
+ZDHHC22	4.66E-01
+NHLRC2	4.67E-01
+HMGA1	4.67E-01
+AP1M1	4.67E-01
+C2orf68	4.67E-01
+NCOR1	4.67E-01
+ATF1	4.67E-01
+AMOTL2	4.67E-01
+HIST2H2AB	4.67E-01
+TNIK	4.67E-01
+ATP6V1D	4.67E-01
+ARHGAP30	4.67E-01
+PCSK9	4.67E-01
+ZNF182	4.67E-01
+MFSD8	4.67E-01
+PGAM2	4.68E-01
+BICD2	4.68E-01
+SLC46A2	4.68E-01
+DHDDS	4.68E-01
+RAB40AL	4.68E-01
+LRRN3	4.68E-01
+FARP1	4.68E-01
+TRAF7	4.68E-01
+IWS1	4.68E-01
+SV2B	4.68E-01
+PLAA	4.68E-01
+DSTN	4.68E-01
+TXNIP	4.68E-01
+GSR	4.68E-01
+HOMEZ	4.68E-01
+C20orf141	4.69E-01
+CD226	4.69E-01
+ABHD5	4.69E-01
+SPTBN2	4.69E-01
+POLR2D	4.69E-01
+PTPRN	4.69E-01
+FAM181A	4.69E-01
+TESC	4.69E-01
+TRAM1L1	4.69E-01
+ARNTL	4.69E-01
+SLC4A7	4.69E-01
+CRISPLD1	4.69E-01
+LY6G5C	4.69E-01
+WBSCR17	4.69E-01
+ZDHHC16	4.70E-01
+CPLX4	4.70E-01
+RCN1	4.70E-01
+UBR7	4.70E-01
+HESX1	4.70E-01
+C18orf54	4.70E-01
+ZNF639	4.70E-01
+ELMOD2	4.70E-01
+U2AF1L4	4.70E-01
+CYP4F22	4.70E-01
+CAPSL	4.70E-01
+ST8SIA5	4.70E-01
+UBR2	4.70E-01
+NANOS3	4.70E-01
+ARL11	4.70E-01
+TXNDC9	4.71E-01
+ACAP3	4.71E-01
+PAPPA	4.71E-01
+FAP	4.71E-01
+YIPF6	4.71E-01
+AGRP	4.71E-01
+FERMT1	4.71E-01
+SLC2A2	4.71E-01
+TAGLN3	4.71E-01
+SNX33	4.71E-01
+KRTAP4-12	4.71E-01
+GREB1	4.71E-01
+GIMAP6	4.71E-01
+KRCC1	4.71E-01
+GFRA3	4.72E-01
+WDR54	4.72E-01
+PPP2CB	4.72E-01
+RACGAP1	4.72E-01
+MARCH7	4.72E-01
+SH3BP4	4.72E-01
+MAP7D1	4.72E-01
+IRGC	4.72E-01
+COX6C	4.72E-01
+MMP24	4.72E-01
+SOCS5	4.72E-01
+PELO	4.72E-01
+FAM159A	4.72E-01
+ZNF304	4.72E-01
+JRKL	4.72E-01
+EPHA2	4.73E-01
+SLC6A7	4.73E-01
+C7orf34	4.73E-01
+TOR1B	4.73E-01
+DCDC2	4.73E-01
+PITPNM1	4.73E-01
+STX17	4.73E-01
+HERC6	4.73E-01
+PREP	4.73E-01
+UBE3C	4.73E-01
+TMEM125	4.73E-01
+AFAP1	4.73E-01
+LYSMD1	4.73E-01
+APOM	4.73E-01
+TOMM7	4.74E-01
+INSM2	4.74E-01
+GLRA4	4.74E-01
+EGLN3	4.74E-01
+TIMM17A	4.74E-01
+HSDL2	4.74E-01
+NAPEPLD	4.74E-01
+C6orf226	4.74E-01
+SKP2	4.74E-01
+GNG4	4.74E-01
+MAGEB1	4.74E-01
+ITM2B	4.74E-01
+WIPF2	4.74E-01
+OSTC	4.74E-01
+KLHL31	4.74E-01
+PTH	4.75E-01
+CXCR2	4.75E-01
+RNF122	4.75E-01
+LPCAT2	4.75E-01
+PER2	4.75E-01
+CAMK1G	4.75E-01
+CIT	4.75E-01
+ENO3	4.75E-01
+SRPK2	4.75E-01
+CALM3	4.75E-01
+TRIM48	4.75E-01
+JMJD7	4.75E-01
+PRRT2	4.75E-01
+THAP10	4.75E-01
+TSPYL1	4.76E-01
+MAG	4.76E-01
+HSPB11	4.76E-01
+DLST	4.76E-01
+PCDHGA10	4.76E-01
+KLHDC8B	4.76E-01
+ABTB1	4.76E-01
+ZBTB1	4.76E-01
+MEGF10	4.76E-01
+NCBP2	4.76E-01
+WFDC3	4.76E-01
+KPNA3	4.76E-01
+ADAMTS10	4.76E-01
+IFNGR1	4.76E-01
+PHF20L1	4.76E-01
+FAM13B	4.77E-01
+SEMA3A	4.77E-01
+TNIP3	4.77E-01
+MED16	4.77E-01
+NDUFB4	4.77E-01
+OSR2	4.77E-01
+DNAJB6	4.77E-01
+RSAD2	4.77E-01
+EHF	4.77E-01
+CMA1	4.77E-01
+C20orf196	4.77E-01
+KLC4	4.77E-01
+REXO2	4.77E-01
+SH3TC2	4.77E-01
+LRRK1	4.78E-01
+HERC3	4.78E-01
+CHN1	4.78E-01
+TTPA	4.78E-01
+SLAMF1	4.78E-01
+DNAJB11	4.78E-01
+SLC39A9	4.78E-01
+RBP3	4.78E-01
+HSPB3	4.78E-01
+CLRN3	4.78E-01
+HECTD2	4.78E-01
+SESTD1	4.78E-01
+ORAOV1	4.78E-01
+HSD17B7	4.78E-01
+LYZL1	4.78E-01
+OR10H1	4.79E-01
+HIST1H3E	4.79E-01
+DEPDC1B	4.79E-01
+ANKRD10	4.79E-01
+RUNDC3A	4.79E-01
+CCL20	4.79E-01
+CCR6	4.79E-01
+TUBG2	4.79E-01
+BCAS3	4.79E-01
+SLFN5	4.79E-01
+KRTAP9-8	4.79E-01
+CD58	4.79E-01
+BTBD9	4.79E-01
+CTDSP1	4.79E-01
+SPSB3	4.80E-01
+CYP7B1	4.80E-01
+FAIM2	4.80E-01
+C1orf146	4.80E-01
+IL3RA	4.80E-01
+CIITA	4.80E-01
+CMTM8	4.80E-01
+GPBP1	4.80E-01
+LRTOMT	4.80E-01
+NDUFB1	4.80E-01
+CD37	4.80E-01
+GMPR	4.80E-01
+TMED9	4.80E-01
+MCM6	4.80E-01
+KCNK2	4.80E-01
+SLC22A18	4.81E-01
+ARHGAP29	4.81E-01
+C4orf51	4.81E-01
+PIK3C3	4.81E-01
+PLEKHA6	4.81E-01
+SPG21	4.81E-01
+CCR10	4.81E-01
+FAM9B	4.81E-01
+RANBP2	4.81E-01
+INTS12	4.81E-01
+RAB37	4.81E-01
+PLXNB1	4.81E-01
+DDX53	4.81E-01
+LENEP	4.81E-01
+TMTC4	4.82E-01
+NUPL1	4.82E-01
+SRP72	4.82E-01
+UVRAG	4.82E-01
+ZNF2	4.82E-01
+SNTB1	4.82E-01
+CA5A	4.82E-01
+NPBWR2	4.82E-01
+REPIN1	4.82E-01
+UNC5C	4.82E-01
+GTF3C2	4.82E-01
+LAMA5	4.82E-01
+VSIG1	4.82E-01
+USP15	4.82E-01
+NLRP13	4.82E-01
+IL19	4.83E-01
+FAM26D	4.83E-01
+LRIG1	4.83E-01
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+TRIM50	4.83E-01
+HNMT	4.83E-01
+THAP2	4.83E-01
+OSGIN2	4.83E-01
+HIST1H2AG	4.83E-01
+REST	4.83E-01
+SPOPL	4.83E-01
+HIST1H1C	4.83E-01
+ARHGEF3	4.83E-01
+GAD1	4.83E-01
+TFDP2	4.83E-01
+ZDHHC21	4.84E-01
+GIF	4.84E-01
+OSBPL11	4.84E-01
+ADCYAP1	4.84E-01
+F3	4.84E-01
+PCP2	4.84E-01
+SNX1	4.84E-01
+C4orf29	4.84E-01
+HIST1H2BI	4.84E-01
+SULT1E1	4.84E-01
+SYT1	4.84E-01
+VAV3	4.84E-01
+NFATC4	4.84E-01
+TAS2R13	4.84E-01
+ALS2CR11	4.85E-01
+OSTN	4.85E-01
+HIGD1A	4.85E-01
+TMEM218	4.85E-01
+ZC3H3	4.85E-01
+TMF1	4.85E-01
+NCK1	4.85E-01
+PIK3R3	4.85E-01
+PRR3	4.85E-01
+CBR4	4.85E-01
+RSL1D1	4.85E-01
+SNRPA	4.85E-01
+RASL12	4.85E-01
+SUSD1	4.85E-01
+RPIA	4.85E-01
+ESAM	4.86E-01
+ZNF320	4.86E-01
+NDNL2	4.86E-01
+OMP	4.86E-01
+ADD2	4.86E-01
+RAPGEFL1	4.86E-01
+MC3R	4.86E-01
+ORAI1	4.86E-01
+C18orf32	4.86E-01
+MYOZ1	4.86E-01
+ZNF143	4.86E-01
+ATP6V1G2	4.86E-01
+HNRNPH3	4.86E-01
+OTOR	4.86E-01
+STX12	4.87E-01
+NLGN1	4.87E-01
+ADIG	4.87E-01
+GPRIN1	4.87E-01
+CCDC88A	4.87E-01
+FNBP1L	4.87E-01
+DAD1	4.87E-01
+ACAP2	4.87E-01
+RAB40B	4.87E-01
+IL13RA2	4.87E-01
+JKAMP	4.87E-01
+HDAC8	4.87E-01
+TRMT61A	4.87E-01
+SH3GLB2	4.87E-01
+HTR3C	4.87E-01
+CCNF	4.88E-01
+INO80B	4.88E-01
+GPN1	4.88E-01
+TMEM120B	4.88E-01
+SCG5	4.88E-01
+ADPGK	4.88E-01
+GHRH	4.88E-01
+RBP7	4.88E-01
+NOP16	4.88E-01
+MRPL27	4.88E-01
+PLCB3	4.88E-01
+S100A14	4.88E-01
+BANF1	4.88E-01
+THAP3	4.88E-01
+TMEM179B	4.89E-01
+LCE2D	4.89E-01
+TXK	4.89E-01
+OR1A1	4.89E-01
+GRAMD3	4.89E-01
+STK38	4.89E-01
+COX16	4.89E-01
+RCHY1	4.89E-01
+UTP11L	4.89E-01
+PJA2	4.89E-01
+B4GALNT1	4.89E-01
+TNFAIP1	4.89E-01
+OR51L1	4.89E-01
+PPARGC1B	4.89E-01
+RIF1	4.89E-01
+TGDS	4.90E-01
+PSD2	4.90E-01
+P2RY13	4.90E-01
+ZSCAN10	4.90E-01
+IFRD1	4.90E-01
+RGS1	4.90E-01
+PIK3CG	4.90E-01
+RIPK2	4.90E-01
+CHRNB3	4.90E-01
+MAS1	4.90E-01
+CD200	4.90E-01
+C16orf87	4.90E-01
+CKS1B	4.90E-01
+ITGAE	4.90E-01
+TOR2A	4.91E-01
+ARFIP1	4.91E-01
+USP30	4.91E-01
+CCL27	4.91E-01
+GNGT2	4.91E-01
+FAM98A	4.91E-01
+PSAPL1	4.91E-01
+AICDA	4.91E-01
+ANKFY1	4.91E-01
+PEX12	4.91E-01
+TRAPPC1	4.91E-01
+HPCAL4	4.91E-01
+PPP2R1B	4.91E-01
+RASAL3	4.91E-01
+GNPNAT1	4.91E-01
+GNRHR	4.92E-01
+TFAM	4.92E-01
+TXNDC15	4.92E-01
+ITFG2	4.92E-01
+C10orf62	4.92E-01
+LPAR3	4.92E-01
+LRRC8B	4.92E-01
+PLA2G12B	4.92E-01
+SEL1L	4.92E-01
+OSTM1	4.92E-01
+MALT1	4.92E-01
+GPSM3	4.92E-01
+IQGAP2	4.92E-01
+KIF23	4.92E-01
+MOGAT3	4.93E-01
+SEC13	4.93E-01
+NDUFC2	4.93E-01
+ZCCHC2	4.93E-01
+NARS	4.93E-01
+NKTR	4.93E-01
+TMIE	4.93E-01
+CDH13	4.93E-01
+KY	4.93E-01
+IL2RA	4.93E-01
+TMEM98	4.93E-01
+TBC1D22A	4.93E-01
+ANKRD50	4.93E-01
+DRG2	4.93E-01
+RAP1B	4.93E-01
+GZMA	4.94E-01
+SP100	4.94E-01
+TMEM196	4.94E-01
+PAK1	4.94E-01
+KIAA1549	4.94E-01
+AGAP2	4.94E-01
+ELAC1	4.94E-01
+WSCD2	4.94E-01
+RWDD1	4.94E-01
+DEPDC5	4.94E-01
+ALDH6A1	4.94E-01
+SLC25A15	4.94E-01
+FATE1	4.94E-01
+GTF3C4	4.94E-01
+PTPLAD2	4.95E-01
+C3orf72	4.95E-01
+SPCS1	4.95E-01
+CYP19A1	4.95E-01
+ERRFI1	4.95E-01
+ABHD14B	4.95E-01
+RNF115	4.95E-01
+XYLT2	4.95E-01
+TSPAN15	4.95E-01
+MED10	4.95E-01
+FDXR	4.95E-01
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+HIST1H4L	4.96E-01
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+ASF1A	4.96E-01
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+ZNF346	5.37E-01
+C17orf58	5.37E-01
+CCNC	5.37E-01
+ACAT2	5.37E-01
+CLPS	5.37E-01
+ZMAT1	5.37E-01
+PLCXD1	5.37E-01
+SLC25A10	5.37E-01
+ZC3HAV1	5.37E-01
+TSEN15	5.37E-01
+C2orf66	5.37E-01
+INHBE	5.38E-01
+RAB38	5.38E-01
+CTNND1	5.38E-01
+SLC6A2	5.38E-01
+MIF4GD	5.38E-01
+IL10	5.38E-01
+CALML6	5.38E-01
+RBPJL	5.38E-01
+MCAT	5.38E-01
+LEFTY1	5.38E-01
+INHBC	5.38E-01
+IL20RA	5.38E-01
+RTP2	5.38E-01
+SIRT7	5.38E-01
+SLC22A4	5.38E-01
+OR7C1	5.39E-01
+KYNU	5.39E-01
+RAB15	5.39E-01
+TMPRSS7	5.39E-01
+TMCO2	5.39E-01
+CCL28	5.39E-01
+C12orf49	5.39E-01
+TAS2R38	5.39E-01
+DEFB136	5.39E-01
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+LCE1B	5.39E-01
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+EIF5A2	5.40E-01
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+ANGPTL7	5.40E-01
+HIST1H2BH	5.40E-01
+VOPP1	5.40E-01
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+PROL1	5.40E-01
+WNK1	5.40E-01
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+LCE2B	5.41E-01
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+UBE2G2	5.41E-01
+CCL8	5.41E-01
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+USP33	5.41E-01
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+IL6	5.41E-01
+RLN1	5.41E-01
+MUM1	5.42E-01
+SPOCK1	5.42E-01
+HERC5	5.42E-01
+PATE2	5.42E-01
+SPINK1	5.42E-01
+ZNF8	5.42E-01
+MMD	5.42E-01
+ELK4	5.42E-01
+CTTN	5.42E-01
+ZNF12	5.42E-01
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+FPR3	5.42E-01
+IGFALS	5.42E-01
+MAP4K1	5.42E-01
+ZNF507	5.42E-01
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+CYTH4	5.43E-01
+CNST	5.43E-01
+ITGAM	5.43E-01
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+SDR39U1	5.43E-01
+NDUFB2	5.43E-01
+ZNF485	5.43E-01
+POLN	5.43E-01
+DGAT2L6	5.43E-01
+POLR3E	5.44E-01
+REV1	5.44E-01
+SLC39A14	5.44E-01
+TCEAL8	5.44E-01
+ANKRD40	5.44E-01
+EMP3	5.44E-01
+ALDH18A1	5.44E-01
+GRAMD1A	5.44E-01
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+DEFB119	5.44E-01
+SCGB1C1	5.44E-01
+PVRL3	5.44E-01
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+IPCEF1	5.44E-01
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+MGP	5.45E-01
+CCK	5.45E-01
+TLR9	5.45E-01
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+ZNHIT1	5.45E-01
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+ZBTB3	5.45E-01
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+ELOVL4	5.45E-01
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+GDPD1	5.46E-01
+TARS	5.46E-01
+COMMD4	5.46E-01
+SS18L2	5.46E-01
+RFX6	5.46E-01
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+SYPL2	5.46E-01
+CIAPIN1	5.46E-01
+DBN1	5.46E-01
+SYT9	5.46E-01
+C11orf71	5.46E-01
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+PDLIM1	5.47E-01
+LIG1	5.47E-01
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+CD274	5.47E-01
+GLT1D1	5.47E-01
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+TOM1L2	5.47E-01
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+DHRS7C	5.48E-01
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+IL13	5.48E-01
+ACOT7	5.48E-01
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+MRGPRE	5.48E-01
+BTRC	5.48E-01
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+GRK6	5.49E-01
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+NOS2	5.49E-01
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+CORO2B	5.49E-01
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+IDI2	5.50E-01
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+HIST1H4H	5.50E-01
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+CDIPT	5.50E-01
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+TIFA	5.50E-01
+RPA2	5.50E-01
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+GGCT	5.51E-01
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+MUCL1	5.51E-01
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+GPR110	5.52E-01
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+SCNN1B	5.52E-01
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+KHK	5.53E-01
+DST	5.54E-01
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+RAB8B	5.56E-01
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+OSM	5.57E-01
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+FGL2	5.59E-01
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+KLHL32	5.64E-01
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+AMBP	5.64E-01
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+RFFL	5.67E-01
+TSPAN6	5.68E-01
+MYOZ2	5.68E-01
+DCDC1	5.68E-01
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+STARD8	5.69E-01
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+FPR1	5.70E-01
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+LGALS1	5.70E-01
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+PLD5	5.70E-01
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+LCT	5.71E-01
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+C16orf92	5.78E-01
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+MYPN	5.78E-01
+OR4D10	5.78E-01
+FXYD3	5.78E-01
+OR14A16	5.78E-01
+SPNS1	5.79E-01
+SLC39A1	5.79E-01
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+LRAT	5.79E-01
+CDK9	5.79E-01
+MAP3K4	5.79E-01
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+DMRT3	5.79E-01
+SNX10	5.79E-01
+CST9	5.79E-01
+OR2F2	5.79E-01
+HIST1H3A	5.79E-01
+JMJD8	5.79E-01
+C11orf80	5.79E-01
+POMZP3	5.79E-01
+MAP1LC3A	5.80E-01
+SSX3	5.80E-01
+RAB31	5.80E-01
+RTL1	5.80E-01
+HTR1E	5.80E-01
+PCOLCE	5.80E-01
+ZNF74	5.80E-01
+C16orf80	5.80E-01
+SYNPO2	5.80E-01
+POF1B	5.80E-01
+ANP32E	5.80E-01
+NRG3	5.80E-01
+PODXL	5.80E-01
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+TRIM62	5.81E-01
+PLCB1	5.81E-01
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+TMEM50A	5.81E-01
+CLK4	5.81E-01
+CHDH	5.81E-01
+MMP26	5.81E-01
+DEFB118	5.81E-01
+TECR	5.81E-01
+APITD1	5.81E-01
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+GPAM	5.81E-01
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+GPX4	5.82E-01
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+FAM63B	5.82E-01
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+PIH1D1	5.82E-01
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+DCTN5	5.83E-01
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+RAPGEF4	5.83E-01
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+ATL3	5.84E-01
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+CSMD3	5.85E-01
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+LEPROT	5.85E-01
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+C1orf186	5.85E-01
+CDKAL1	5.85E-01
+TRO	5.85E-01
+MYLK3	5.85E-01
+GPR179	5.85E-01
+SRD5A3	5.86E-01
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+SLC35B4	5.86E-01
+OR51A7	5.86E-01
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+TTLL7	5.87E-01
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+TSPAN17	5.89E-01
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+ST3GAL3	5.89E-01
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+CTNNBL1	5.89E-01
+OXNAD1	5.89E-01
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+ANKRD12	5.90E-01
+KDELC1	5.90E-01
+OR10J5	5.90E-01
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+C10orf113	5.90E-01
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+ZNF260	5.90E-01
+HIST1H2AL	5.91E-01
+MEF2A	5.91E-01
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+GLTSCR2	5.91E-01
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+RUFY3	5.91E-01
+KRTAP6-2	5.91E-01
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+DOCK11	6.20E-01
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+NNMT	6.20E-01
+RBM45	6.20E-01
+UPK1B	6.20E-01
+IFNA2	6.20E-01
+OR2C1	6.20E-01
+LCN8	6.21E-01
+PARVA	6.21E-01
+AHRR	6.21E-01
+SP140L	6.21E-01
+C19orf48	6.21E-01
+ZFAND2A	6.21E-01
+CTTNBP2NL	6.21E-01
+DLG1	6.21E-01
+NFU1	6.21E-01
+EPYC	6.21E-01
+IFI27	6.21E-01
+PTGES2	6.21E-01
+IL1RAP	6.21E-01
+KRTAP12-1	6.21E-01
+MOGAT1	6.21E-01
+NDUFB7	6.22E-01
+ANKDD1A	6.22E-01
+ACSF2	6.22E-01
+MGEA5	6.22E-01
+ARL13A	6.22E-01
+BEX5	6.22E-01
+GOPC	6.22E-01
+DGCR14	6.22E-01
+TCF12	6.22E-01
+COPS7B	6.22E-01
+CEBPG	6.22E-01
+CD83	6.22E-01
+RNF7	6.22E-01
+C1orf53	6.22E-01
+SELM	6.23E-01
+SPOCK3	6.23E-01
+RAB11FIP2	6.23E-01
+HPDL	6.23E-01
+TNK1	6.23E-01
+CIB2	6.23E-01
+KIDINS220	6.23E-01
+DTL	6.23E-01
+C15orf43	6.23E-01
+ICT1	6.23E-01
+ADAMTS7	6.23E-01
+MAP1LC3C	6.23E-01
+G6PC2	6.23E-01
+OR1F1	6.23E-01
+CCDC58	6.23E-01
+CD101	6.24E-01
+CD5L	6.24E-01
+IL18RAP	6.24E-01
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+RP9	6.24E-01
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+NKAIN2	6.24E-01
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+GIN1	6.24E-01
+OR5AP2	6.24E-01
+IL17RA	6.24E-01
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+RHCE	6.24E-01
+ZNF383	6.25E-01
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+PBK	6.25E-01
+VPREB1	6.25E-01
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+MT3	6.25E-01
+PCDHGA12	6.25E-01
+AGR2	6.25E-01
+TNC	6.25E-01
+ZNF335	6.25E-01
+C7orf25	6.25E-01
+MYL9	6.26E-01
+NSMCE4A	6.26E-01
+DEFB121	6.26E-01
+SCGB3A2	6.26E-01
+IMMP1L	6.26E-01
+MAP7	6.26E-01
+CISD1	6.26E-01
+MEP1A	6.26E-01
+GFI1B	6.26E-01
+EHMT2	6.26E-01
+TAF1A	6.26E-01
+VARS	6.26E-01
+PTPLA	6.26E-01
+B4GALT3	6.26E-01
+CRYL1	6.27E-01
+ZNF623	6.27E-01
+ASB17	6.27E-01
+STX5	6.27E-01
+CYP1A1	6.27E-01
+HDGF	6.27E-01
+GAL3ST4	6.27E-01
+PCDHGA8	6.27E-01
+ACOT13	6.27E-01
+CST5	6.27E-01
+ZNF500	6.27E-01
+REEP5	6.27E-01
+ZNF585A	6.27E-01
+SYPL1	6.27E-01
+ATP5F1	6.27E-01
+TRIM63	6.28E-01
+ADRBK2	6.28E-01
+ANGPTL5	6.28E-01
+ZDHHC19	6.28E-01
+FABP1	6.28E-01
+MTG1	6.28E-01
+FUT3	6.28E-01
+TRIM13	6.28E-01
+HLA-DQA1	6.28E-01
+CASP3	6.28E-01
+TRIM29	6.28E-01
+SH3PXD2B	6.28E-01
+PF4	6.28E-01
+KDM2B	6.28E-01
+ZNF253	6.29E-01
+CIB1	6.29E-01
+LRIG3	6.29E-01
+FN3K	6.29E-01
+USP14	6.29E-01
+CHST8	6.29E-01
+PNPLA4	6.29E-01
+OR1K1	6.29E-01
+TRMT12	6.29E-01
+LNX2	6.29E-01
+SH2D4A	6.29E-01
+C9orf16	6.29E-01
+LAT2	6.29E-01
+PGBD2	6.29E-01
+KRTAP19-8	6.29E-01
+OR6B3	6.30E-01
+OR51T1	6.30E-01
+ZNF517	6.30E-01
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+DOCK8	6.30E-01
+MDC1	6.30E-01
+GP1BA	6.30E-01
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+ARFGAP1	6.30E-01
+RNASE8	6.30E-01
+PSTPIP2	6.30E-01
+TXNDC11	6.30E-01
+GPR146	6.30E-01
+HIST1H4A	6.31E-01
+IL22RA1	6.31E-01
+PLEKHG1	6.31E-01
+NDUFS6	6.31E-01
+PDP1	6.31E-01
+UNC5CL	6.31E-01
+LIPF	6.31E-01
+IQCH	6.31E-01
+HINT2	6.31E-01
+PTAFR	6.31E-01
+LAMB1	6.31E-01
+CCDC23	6.31E-01
+SPHAR	6.31E-01
+NARFL	6.31E-01
+CCDC66	6.31E-01
+RNF43	6.32E-01
+SEMA5A	6.32E-01
+RASGEF1C	6.32E-01
+C11orf65	6.32E-01
+NUCB1	6.32E-01
+FAM131C	6.32E-01
+STX16	6.32E-01
+BLVRA	6.32E-01
+SIM2	6.32E-01
+DEFB128	6.32E-01
+TCTEX1D1	6.32E-01
+CXorf36	6.32E-01
+KRTAP12-2	6.32E-01
+PKD2L1	6.32E-01
+FLVCR2	6.33E-01
+KBTBD8	6.33E-01
+HARS2	6.33E-01
+TM4SF19	6.33E-01
+TAS2R10	6.33E-01
+ARL16	6.33E-01
+NAT8	6.33E-01
+DBR1	6.33E-01
+FKBP11	6.33E-01
+RHBDL3	6.33E-01
+SPPL2A	6.33E-01
+C1orf162	6.33E-01
+PRLHR	6.33E-01
+HCRTR1	6.33E-01
+ARL6IP1	6.33E-01
+ADORA2A	6.34E-01
+CCNL2	6.34E-01
+DEPDC7	6.34E-01
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+RAD18	6.34E-01
+NDST4	6.34E-01
+EIF5B	6.34E-01
+KIAA1429	6.34E-01
+HIST1H3G	6.34E-01
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+CD300LB	6.34E-01
+CDYL	6.34E-01
+OXTR	6.34E-01
+AANAT	6.35E-01
+PPAPDC1B	6.35E-01
+RHOF	6.35E-01
+FAM135A	6.35E-01
+TUSC3	6.35E-01
+AURKB	6.35E-01
+NMBR	6.35E-01
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+CCR9	6.35E-01
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+SAT2	6.35E-01
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+OR7D2	6.39E-01
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+FAM71B	6.41E-01
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+OR1N2	6.45E-01
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+SLC22A13	6.61E-01
+FGF5	6.62E-01
+CSTB	6.62E-01
+S100A5	6.62E-01
+ZNF575	6.62E-01
+SLC33A1	6.62E-01
+CMC1	6.62E-01
+FHDC1	6.62E-01
+IFNA7	6.62E-01
+ZNF529	6.62E-01
+TRPA1	6.62E-01
+WDR12	6.62E-01
+TRA2A	6.62E-01
+FBXL4	6.62E-01
+MAP4K3	6.62E-01
+OR52W1	6.62E-01
+MSMB	6.63E-01
+PRMT7	6.63E-01
+BCL7C	6.63E-01
+TFPI2	6.63E-01
+LCNL1	6.63E-01
+POPDC2	6.63E-01
+CT62	6.63E-01
+RNF32	6.63E-01
+CIRH1A	6.63E-01
+XKR9	6.63E-01
+DDX56	6.63E-01
+UBC	6.63E-01
+CDH15	6.63E-01
+CAMLG	6.63E-01
+OR5B21	6.64E-01
+EIF2AK2	6.64E-01
+NCKAP1L	6.64E-01
+SLCO6A1	6.64E-01
+SPINT2	6.64E-01
+PCBD2	6.64E-01
+SCRN1	6.64E-01
+BCKDK	6.64E-01
+C9orf114	6.64E-01
+C15orf53	6.64E-01
+SMPD2	6.64E-01
+OR10C1	6.64E-01
+ZNF491	6.64E-01
+KRTAP10-1	6.64E-01
+CABP5	6.64E-01
+RBM18	6.65E-01
+NAA38	6.65E-01
+TMCO6	6.65E-01
+ZNF621	6.65E-01
+OR52B6	6.65E-01
+DEFB129	6.65E-01
+FAM107B	6.65E-01
+NUP37	6.65E-01
+ICK	6.65E-01
+PTPRK	6.65E-01
+NMUR2	6.65E-01
+PPIB	6.65E-01
+ZNF682	6.65E-01
+KIF2C	6.65E-01
+CRYGN	6.66E-01
+OR4E2	6.66E-01
+GEMIN6	6.66E-01
+ZNF786	6.66E-01
+PIP	6.66E-01
+OCM2	6.66E-01
+AGFG2	6.66E-01
+SLC23A3	6.66E-01
+RGS17	6.66E-01
+S100A1	6.66E-01
+TEDDM1	6.66E-01
+GLT6D1	6.66E-01
+TAB1	6.66E-01
+IAH1	6.66E-01
+IGDCC4	6.66E-01
+SLC27A1	6.67E-01
+VIP	6.67E-01
+OR13H1	6.67E-01
+TMC7	6.67E-01
+LYNX1	6.67E-01
+ZNF48	6.67E-01
+ARHGAP12	6.67E-01
+HIST1H2AM	6.67E-01
+ZKSCAN3	6.67E-01
+TOX2	6.67E-01
+EPS15	6.67E-01
+SH2B1	6.67E-01
+MS4A6E	6.67E-01
+MFSD10	6.67E-01
+PLD3	6.68E-01
+RASGRP4	6.68E-01
+SPIRE1	6.68E-01
+SEMA5B	6.68E-01
+CPSF1	6.68E-01
+KDELC2	6.68E-01
+SOD2	6.68E-01
+OXR1	6.68E-01
+REG4	6.68E-01
+OR10H3	6.68E-01
+OR6T1	6.68E-01
+LCE2C	6.68E-01
+CDK3	6.68E-01
+OR5M10	6.68E-01
+TUFT1	6.68E-01
+TMEM208	6.69E-01
+GALR1	6.69E-01
+MRPS27	6.69E-01
+TMEM150B	6.69E-01
+CMTM4	6.69E-01
+CHGA	6.69E-01
+SMCP	6.69E-01
+ACSS1	6.69E-01
+CYP2R1	6.69E-01
+RABL2A	6.69E-01
+C14orf28	6.69E-01
+TM4SF1	6.69E-01
+ADD1	6.69E-01
+NIPSNAP3B	6.69E-01
+PARP12	6.70E-01
+NKIRAS2	6.70E-01
+PRSS35	6.70E-01
+PPIL1	6.70E-01
+SNCAIP	6.70E-01
+CEP68	6.70E-01
+ANKS4B	6.70E-01
+ZNF502	6.70E-01
+CXorf66	6.70E-01
+OR8B8	6.70E-01
+CORO6	6.70E-01
+C15orf32	6.70E-01
+HEBP1	6.70E-01
+MYBPHL	6.70E-01
+SEPHS2	6.70E-01
+PARP11	6.71E-01
+B3GNT8	6.71E-01
+SEL1L3	6.71E-01
+SLC22A16	6.71E-01
+AMOTL1	6.71E-01
+CC2D2B	6.71E-01
+C19orf70	6.71E-01
+NUDT2	6.71E-01
+NDUFS4	6.71E-01
+HYAL3	6.71E-01
+GSTT1	6.71E-01
+TIMM10	6.71E-01
+NT5M	6.71E-01
+XRCC3	6.71E-01
+GALNT12	6.72E-01
+SNAPIN	6.72E-01
+C2CD2	6.72E-01
+FARSA	6.72E-01
+WFDC9	6.72E-01
+LARP4	6.72E-01
+RRP1B	6.72E-01
+OR6N1	6.72E-01
+HAL	6.72E-01
+RPUSD1	6.72E-01
+ZNF280D	6.72E-01
+DNAJC19	6.72E-01
+NOP14	6.72E-01
+OR2H2	6.72E-01
+SYT16	6.72E-01
+VSIG2	6.73E-01
+CDCA5	6.73E-01
+DGCR6L	6.73E-01
+FAM24B	6.73E-01
+FASTK	6.73E-01
+ADAMTSL1	6.73E-01
+SUSD4	6.73E-01
+ITIH3	6.73E-01
+GPR32	6.73E-01
+RNASE3	6.73E-01
+TMEM135	6.73E-01
+PALMD	6.73E-01
+CXorf38	6.73E-01
+LSM3	6.73E-01
+EARS2	6.74E-01
+LIN7A	6.74E-01
+NRSN1	6.74E-01
+AURKA	6.74E-01
+MRPS24	6.74E-01
+PNCK	6.74E-01
+CLEC4E	6.74E-01
+HEPN1	6.74E-01
+YARS	6.74E-01
+ARRDC5	6.74E-01
+BCAM	6.74E-01
+PNMT	6.74E-01
+OR1E2	6.74E-01
+CCDC8	6.74E-01
+S100A2	6.74E-01
+SASS6	6.75E-01
+XRN1	6.75E-01
+NUBP2	6.75E-01
+PIGM	6.75E-01
+OR7G1	6.75E-01
+PLA2G16	6.75E-01
+RAB3IL1	6.75E-01
+POLE4	6.75E-01
+ZNF708	6.75E-01
+PRTG	6.75E-01
+GKN1	6.75E-01
+ELOVL3	6.75E-01
+SMTN	6.75E-01
+HMCN1	6.75E-01
+MT1F	6.76E-01
+GALNT3	6.76E-01
+TMEM147	6.76E-01
+OR52A1	6.76E-01
+SIGLEC5	6.76E-01
+SSSCA1	6.76E-01
+THOC5	6.76E-01
+PLN	6.76E-01
+OR10T2	6.76E-01
+PNMAL1	6.76E-01
+IFNW1	6.76E-01
+CCNE2	6.76E-01
+ZADH2	6.76E-01
+RBP5	6.76E-01
+DNAJC5B	6.76E-01
+C5orf58	6.77E-01
+RUFY2	6.77E-01
+LSM2	6.77E-01
+MYL10	6.77E-01
+DDI1	6.77E-01
+TACC3	6.77E-01
+GTSF1L	6.77E-01
+EEA1	6.77E-01
+IPO8	6.77E-01
+GPR123	6.77E-01
+DOPEY1	6.77E-01
+DIRC1	6.77E-01
+SCAMP4	6.77E-01
+MYL5	6.77E-01
+ZSCAN4	6.78E-01
+NUP93	6.78E-01
+CARKD	6.78E-01
+SENP7	6.78E-01
+MMRN2	6.78E-01
+PEX16	6.78E-01
+SIDT2	6.78E-01
+SCYL1	6.78E-01
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+ANKS6	6.78E-01
+ARHGAP33	6.78E-01
+NDUFA13	6.78E-01
+MCEE	6.78E-01
+OR5AU1	6.79E-01
+ZIM2	6.79E-01
+DPPA4	6.79E-01
+SLC44A5	6.79E-01
+S100A16	6.79E-01
+ART4	6.79E-01
+TMEM145	6.79E-01
+PLCB4	6.79E-01
+ZXDC	6.79E-01
+SGK223	6.79E-01
+RNF175	6.79E-01
+TEAD2	6.79E-01
+MT2A	6.79E-01
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+OR10K1	6.80E-01
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+HACE1	6.80E-01
+OR4N2	6.80E-01
+CYTIP	6.80E-01
+NTAN1	6.80E-01
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+OR1J4	6.80E-01
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+OR4A5	6.80E-01
+MANSC1	6.80E-01
+ICOSLG	6.80E-01
+ABL2	6.80E-01
+SVIP	6.80E-01
+IKBKE	6.80E-01
+C22orf24	6.81E-01
+GLRX2	6.81E-01
+NKAIN4	6.81E-01
+VAT1L	6.81E-01
+UQCRC2	6.81E-01
+SEC14L1	6.81E-01
+PVRIG	6.81E-01
+OR5F1	6.81E-01
+SARS2	6.81E-01
+CCDC112	6.81E-01
+SLC4A9	6.81E-01
+TBL3	6.81E-01
+RADIL	6.81E-01
+PDLIM5	6.81E-01
+GPR124	6.82E-01
+ISLR	6.82E-01
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+STX7	6.82E-01
+SLC22A3	6.82E-01
+GIMAP4	6.82E-01
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+CLK3	6.82E-01
+C11orf52	6.82E-01
+OR13G1	6.82E-01
+DYTN	6.82E-01
+PDCD11	6.82E-01
+RCVRN	6.82E-01
+TM4SF5	6.82E-01
+PLCL1	6.83E-01
+MRGPRX4	6.83E-01
+UCHL5	6.83E-01
+OR52I2	6.83E-01
+C4orf36	6.83E-01
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+TTC30A	6.83E-01
+TRAK1	6.83E-01
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+IFNA6	6.84E-01
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+PI4KA	6.84E-01
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+IFNA5	6.84E-01
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+TFF3	6.84E-01
+ZNF234	6.84E-01
+CDC27	6.84E-01
+PUS1	6.84E-01
+OR13C5	6.84E-01
+RASGRP3	6.85E-01
+MZF1	6.85E-01
+OR6C2	6.85E-01
+RIT2	6.85E-01
+ZNF624	6.85E-01
+TFF1	6.85E-01
+MCM3AP	6.85E-01
+USP38	6.85E-01
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+KBTBD7	6.85E-01
+RNASEL	6.85E-01
+CNPY1	6.85E-01
+GPD1	6.85E-01
+PIP5K1B	6.85E-01
+CYP26A1	6.86E-01
+ST6GALNAC3	6.86E-01
+PABPN1L	6.86E-01
+OR2G3	6.86E-01
+WBP2NL	6.86E-01
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+GPR75	6.86E-01
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+ZNF550	6.86E-01
+GSTM1	6.86E-01
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+BMP1	6.87E-01
+ASB2	6.87E-01
+SCGB1D2	6.87E-01
+NUP62CL	6.87E-01
+ZSWIM5	6.87E-01
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+ROBO1	6.87E-01
+EMR3	6.87E-01
+CFHR2	6.87E-01
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+CD300C	6.87E-01
+OR10X1	6.87E-01
+LRRC66	6.88E-01
+PPP3R2	6.88E-01
+RBMS2	6.88E-01
+FMO1	6.88E-01
+ZNF585B	6.88E-01
+GALNT4	6.88E-01
+CRIPT	6.88E-01
+OR4K2	6.88E-01
+USP43	6.88E-01
+CNIH4	6.88E-01
+NDUFB3	6.88E-01
+OR10Q1	6.88E-01
+NYNRIN	6.88E-01
+HIGD1B	6.88E-01
+IGFL3	6.89E-01
+MRPS16	6.89E-01
+ZNF474	6.89E-01
+SMC5	6.89E-01
+TIGD2	6.89E-01
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+ZNF133	6.89E-01
+WDFY1	6.89E-01
+TOP2A	6.89E-01
+TNFRSF17	6.89E-01
+C11orf31	6.89E-01
+MSRB3	6.89E-01
+ZNF259	6.89E-01
+TBC1D21	6.89E-01
+DHFR	6.89E-01
+IL17RD	6.90E-01
+DEFB132	6.90E-01
+ZNF318	6.90E-01
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+KLC1	6.90E-01
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+MBOAT7	6.90E-01
+MRPL50	6.90E-01
+MC5R	6.90E-01
+TDGF1	6.90E-01
+UBE2V2	6.90E-01
+IL12B	6.90E-01
+GXYLT2	6.90E-01
+FAM166B	6.91E-01
+CST3	6.91E-01
+PPP2R3B	6.91E-01
+TAS2R7	6.91E-01
+QRFP	6.91E-01
+MYRIP	6.91E-01
+C7orf10	6.91E-01
+CCNDBP1	6.91E-01
+SDPR	6.91E-01
+JAKMIP3	6.91E-01
+VAPA	6.91E-01
+JAM3	6.91E-01
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+RAI14	6.92E-01
+ANKZF1	6.92E-01
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+GRWD1	6.92E-01
+P2RY2	6.92E-01
+TSPAN32	6.92E-01
+AMIGO3	6.92E-01
+OR5AR1	6.92E-01
+SLC6A5	6.92E-01
+METTL10	6.92E-01
+CRYGA	6.92E-01
+PMPCA	6.92E-01
+RHOBTB3	6.93E-01
+PYCARD	6.93E-01
+MPP4	6.93E-01
+CCDC114	6.93E-01
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+CD3E	6.93E-01
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+SORCS2	6.93E-01
+KRTAP11-1	6.94E-01
+ZNF441	6.94E-01
+TIMM22	6.94E-01
+SLC25A40	6.94E-01
+STARD4	6.94E-01
+OR5AS1	6.94E-01
+SPINK9	6.94E-01
+OR4C3	6.94E-01
+TFF2	6.94E-01
+MS4A1	6.94E-01
+METTL2A	6.94E-01
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+OR52L1	6.94E-01
+WFDC13	6.94E-01
+FTSJ3	6.95E-01
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+MDN1	6.95E-01
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+GPR133	6.95E-01
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+PTCD2	6.95E-01
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+HR	6.95E-01
+KRTAP1-5	6.96E-01
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+TMEM70	6.96E-01
+ZNF354B	6.96E-01
+POM121L12	6.96E-01
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+SMOC2	6.96E-01
+PEG3	6.96E-01
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+ZNF534	6.97E-01
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+CD200R1L	6.98E-01
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+SEPT10	6.98E-01
+KL	6.98E-01
+ZNF561	6.98E-01
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+CHRDL1	6.98E-01
+IKBKB	6.98E-01
+RGAG4	6.98E-01
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+SP140	6.99E-01
+CIDEB	6.99E-01
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+CGREF1	7.00E-01
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+ABHD10	7.02E-01
+USH1G	7.02E-01
+C8orf86	7.02E-01
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+IQCF2	7.03E-01
+TRHR	7.03E-01
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+FFAR1	7.03E-01
+CRYGB	7.03E-01
+ROPN1	7.03E-01
+CPM	7.03E-01
+CSGALNACT2	7.03E-01
+OR1B1	7.03E-01
+GCA	7.03E-01
+ZNF165	7.03E-01
+TPMT	7.03E-01
+MRPL51	7.03E-01
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+SEMA4D	7.87E-01
+PON1	7.87E-01
+MRPS28	7.87E-01
+MYOZ3	7.87E-01
+LCE3E	7.87E-01
+RBM11	7.87E-01
+SEC31A	7.87E-01
+AADACL4	7.87E-01
+CWF19L2	7.87E-01
+OR4D5	7.87E-01
+ZNF157	7.87E-01
+RMI1	7.87E-01
+HS1BP3	7.87E-01
+TM6SF2	7.88E-01
+OR8D4	7.88E-01
+TNIP2	7.88E-01
+TRIM16L	7.88E-01
+ITGA10	7.88E-01
+RSPH1	7.88E-01
+AP4M1	7.88E-01
+NMS	7.88E-01
+AURKAIP1	7.88E-01
+UBE2U	7.88E-01
+MORN1	7.88E-01
+BANF2	7.88E-01
+PINK1	7.88E-01
+VIPR1	7.88E-01
+KRR1	7.88E-01
+RAB28	7.89E-01
+C2orf61	7.89E-01
+SPNS3	7.89E-01
+NDC80	7.89E-01
+HORMAD1	7.89E-01
+C2orf44	7.89E-01
+OTUD3	7.89E-01
+IARS2	7.89E-01
+OR4M2	7.89E-01
+CMTM5	7.89E-01
+OR5V1	7.89E-01
+ENAM	7.89E-01
+CCDC153	7.89E-01
+PIWIL4	7.89E-01
+C12orf50	7.90E-01
+GNB5	7.90E-01
+HCLS1	7.90E-01
+PGM2	7.90E-01
+C11orf49	7.90E-01
+TYW3	7.90E-01
+PDIA5	7.90E-01
+SNX7	7.90E-01
+COMMD7	7.90E-01
+MTHFD1	7.90E-01
+SYT5	7.90E-01
+LRRC49	7.90E-01
+SMUG1	7.90E-01
+HSPBAP1	7.90E-01
+NME7	7.90E-01
+SHKBP1	7.91E-01
+C15orf60	7.91E-01
+MCCD1	7.91E-01
+CHRDL2	7.91E-01
+LCN6	7.91E-01
+IFNA13	7.91E-01
+CDKL1	7.91E-01
+ZNF429	7.91E-01
+CNTF	7.91E-01
+FTL	7.91E-01
+TM7SF3	7.91E-01
+LRTM1	7.91E-01
+TACR3	7.91E-01
+PCDH12	7.91E-01
+FBXO4	7.92E-01
+LRPPRC	7.92E-01
+C2orf40	7.92E-01
+GPX8	7.92E-01
+C20orf85	7.92E-01
+CD68	7.92E-01
+MRPL35	7.92E-01
+TRMT5	7.92E-01
+LY86	7.92E-01
+SGSM3	7.92E-01
+APOBEC3D	7.92E-01
+CSN3	7.92E-01
+TFCP2	7.92E-01
+NOL11	7.92E-01
+NMRAL1	7.92E-01
+NUP210	7.93E-01
+PHOSPHO2	7.93E-01
+GRB7	7.93E-01
+SLCO1B3	7.93E-01
+AMDHD1	7.93E-01
+NFX1	7.93E-01
+C3orf33	7.93E-01
+ANKFN1	7.93E-01
+TMEM79	7.93E-01
+SLC38A11	7.93E-01
+RAB5C	7.93E-01
+ATRIP	7.93E-01
+FAM83C	7.93E-01
+MS4A2	7.93E-01
+ARHGAP15	7.94E-01
+SYNPO2L	7.94E-01
+SCFD2	7.94E-01
+ACOT12	7.94E-01
+DTX3L	7.94E-01
+LIFR	7.94E-01
+IFNA17	7.94E-01
+ACOT6	7.94E-01
+IP6K2	7.94E-01
+CARS	7.94E-01
+PSTPIP1	7.94E-01
+PGM3	7.94E-01
+DMP1	7.94E-01
+SNX25	7.94E-01
+DDC	7.94E-01
+C3orf62	7.95E-01
+FABP5	7.95E-01
+ST6GAL2	7.95E-01
+SPHK2	7.95E-01
+ZNF420	7.95E-01
+C1orf111	7.95E-01
+CA1	7.95E-01
+GPR141	7.95E-01
+OR1E1	7.95E-01
+TMX4	7.95E-01
+C1orf210	7.95E-01
+TAS2R3	7.95E-01
+FRZB	7.95E-01
+ACPP	7.95E-01
+NIF3L1	7.96E-01
+NBR1	7.96E-01
+FNDC8	7.96E-01
+TREML4	7.96E-01
+FBXO47	7.96E-01
+FUZ	7.96E-01
+LRRC31	7.96E-01
+TAS2R4	7.96E-01
+LYPD3	7.96E-01
+VIL1	7.96E-01
+EIF2AK1	7.96E-01
+C4orf22	7.96E-01
+OR51G1	7.96E-01
+KRTAP27-1	7.96E-01
+ULBP1	7.96E-01
+MVP	7.97E-01
+IDE	7.97E-01
+TBC1D23	7.97E-01
+OR2H1	7.97E-01
+PPIC	7.97E-01
+CYP4Z1	7.97E-01
+FAM118B	7.97E-01
+C11orf1	7.97E-01
+PLEKHH1	7.97E-01
+QRSL1	7.97E-01
+ROPN1L	7.97E-01
+TRPM7	7.97E-01
+ZNF175	7.97E-01
+TRPM2	7.97E-01
+SIGLEC9	7.98E-01
+ZNF14	7.98E-01
+LMBR1	7.98E-01
+KHNYN	7.98E-01
+C16orf3	7.98E-01
+RNF25	7.98E-01
+LY6G6F	7.98E-01
+NAA20	7.98E-01
+ZNF132	7.98E-01
+TMEM209	7.98E-01
+SHISA3	7.98E-01
+CDH19	7.98E-01
+LSS	7.98E-01
+PDK1	7.98E-01
+SLC30A9	7.98E-01
+CSGALNACT1	7.99E-01
+LIPK	7.99E-01
+ARHGEF10	7.99E-01
+CDHR2	7.99E-01
+TBCD	7.99E-01
+KIF18A	7.99E-01
+KRTAP5-1	7.99E-01
+PNPLA5	7.99E-01
+PTTG2	7.99E-01
+OR2B3	7.99E-01
+OPTC	7.99E-01
+THEM5	7.99E-01
+ME3	7.99E-01
+OR14J1	7.99E-01
+MRPS30	8.00E-01
+PADI2	8.00E-01
+KIF22	8.00E-01
+OR6X1	8.00E-01
+SLMO1	8.00E-01
+TIPIN	8.00E-01
+C9orf129	8.00E-01
+KRTAP1-1	8.00E-01
+TMEM175	8.00E-01
+CTAG2	8.00E-01
+TOR1AIP1	8.00E-01
+C12orf52	8.00E-01
+DYDC2	8.00E-01
+GYS1	8.00E-01
+LSP1	8.00E-01
+PI15	8.01E-01
+PLCD4	8.01E-01
+KLRK1	8.01E-01
+AUH	8.01E-01
+ATXN3L	8.01E-01
+CENPE	8.01E-01
+LYPD5	8.01E-01
+DEPDC4	8.01E-01
+STRADA	8.01E-01
+ZKSCAN5	8.01E-01
+FBXO40	8.01E-01
+OR13D1	8.01E-01
+PDK4	8.01E-01
+PHLDB2	8.01E-01
+TRIM40	8.02E-01
+ETV7	8.02E-01
+CRTAM	8.02E-01
+ODF4	8.02E-01
+DDIT4L	8.02E-01
+DBH	8.02E-01
+LIMCH1	8.02E-01
+SLC38A10	8.02E-01
+PLCE1	8.02E-01
+SUSD5	8.02E-01
+KIAA1324L	8.02E-01
+ZNF584	8.02E-01
+LUZP4	8.02E-01
+REG1B	8.02E-01
+PNMA5	8.02E-01
+HIP1R	8.03E-01
+RHOT2	8.03E-01
+PRAMEF12	8.03E-01
+DFNB59	8.03E-01
+CDC20	8.03E-01
+PLEKHG5	8.03E-01
+CST7	8.03E-01
+KLRB1	8.03E-01
+ACSL6	8.03E-01
+TRUB1	8.03E-01
+EDEM3	8.03E-01
+PGM1	8.03E-01
+WDR6	8.03E-01
+ZNF782	8.03E-01
+FAM133B	8.04E-01
+LPO	8.04E-01
+PCDHA5	8.04E-01
+TTLL1	8.04E-01
+OR2B2	8.04E-01
+UBASH3A	8.04E-01
+IFNA10	8.04E-01
+PSTK	8.04E-01
+MFSD1	8.04E-01
+CLPB	8.04E-01
+SYF2	8.04E-01
+OR6C4	8.04E-01
+ZNF667	8.04E-01
+C15orf57	8.04E-01
+OR7D4	8.04E-01
+PIGZ	8.05E-01
+OR5P2	8.05E-01
+OR51I1	8.05E-01
+PCDHA6	8.05E-01
+LMBR1L	8.05E-01
+SEPT12	8.05E-01
+ZNF92	8.05E-01
+ANKLE2	8.05E-01
+ETV2	8.05E-01
+OR8B3	8.05E-01
+TMEM177	8.05E-01
+CYSLTR2	8.05E-01
+RTN4	8.05E-01
+ALPK3	8.05E-01
+BEND7	8.06E-01
+TAAR2	8.06E-01
+COMMD10	8.06E-01
+WDFY2	8.06E-01
+FRAS1	8.06E-01
+DNAJC9	8.06E-01
+RILPL1	8.06E-01
+NUMB	8.06E-01
+OCEL1	8.06E-01
+ERI1	8.06E-01
+OR8D1	8.06E-01
+OR6C76	8.06E-01
+ARMC6	8.06E-01
+PLIN3	8.06E-01
+SPTA1	8.06E-01
+MMP17	8.07E-01
+OR5T2	8.07E-01
+COX4I2	8.07E-01
+CCDC122	8.07E-01
+TIAM2	8.07E-01
+CCR5	8.07E-01
+OR4A47	8.07E-01
+ZNF446	8.07E-01
+IL1A	8.07E-01
+TMEM8A	8.07E-01
+OR5K3	8.07E-01
+FAM173B	8.07E-01
+TAS2R60	8.07E-01
+OR8H2	8.07E-01
+MEA1	8.08E-01
+TIGD3	8.08E-01
+ARHGEF16	8.08E-01
+TCN2	8.08E-01
+TMED1	8.08E-01
+MLPH	8.08E-01
+DAND5	8.08E-01
+CMTM2	8.08E-01
+SLC22A15	8.08E-01
+DSCC1	8.08E-01
+RSPH3	8.08E-01
+C12orf29	8.08E-01
+CCR3	8.08E-01
+SGMS2	8.08E-01
+CRYBB3	8.08E-01
+OCIAD2	8.09E-01
+DYNC2LI1	8.09E-01
+IFNA8	8.09E-01
+UIMC1	8.09E-01
+CLECL1	8.09E-01
+SORBS1	8.09E-01
+SFT2D2	8.09E-01
+MYCBPAP	8.09E-01
+LGALS14	8.09E-01
+AIFM2	8.09E-01
+EHBP1L1	8.09E-01
+LRSAM1	8.09E-01
+OR2L2	8.09E-01
+ECHDC2	8.09E-01
+CPSF3L	8.10E-01
+TMEM99	8.10E-01
+RIPK3	8.10E-01
+UROC1	8.10E-01
+GLYCTK	8.10E-01
+ZNF674	8.10E-01
+KANK1	8.10E-01
+OR51D1	8.10E-01
+OR6C65	8.10E-01
+OR5L2	8.10E-01
+DPY19L3	8.10E-01
+GPRASP1	8.10E-01
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+RTN4IP1	8.11E-01
+HOOK1	8.11E-01
+ESD	8.11E-01
+MRPL22	8.11E-01
+NBN	8.11E-01
+CEACAM3	8.11E-01
+HUS1	8.11E-01
+KIAA1033	8.11E-01
+SLC9A8	8.11E-01
+ANO4	8.11E-01
+NCOA7	8.11E-01
+TDG	8.11E-01
+DHX29	8.11E-01
+CDHR5	8.11E-01
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+SPANXN2	8.12E-01
+RNASE6	8.12E-01
+ASGR1	8.12E-01
+KRTAP5-9	8.12E-01
+PDCD1LG2	8.12E-01
+DGAT1	8.12E-01
+PCDHB6	8.12E-01
+ZNF79	8.12E-01
+ATP1B4	8.12E-01
+FAAH	8.12E-01
+RHBDL2	8.12E-01
+SLC22A14	8.12E-01
+GLOD4	8.12E-01
+CDKN3	8.12E-01
+PLA2G4F	8.13E-01
+KLHDC7A	8.13E-01
+C5orf20	8.13E-01
+SLC1A7	8.13E-01
+MCM4	8.13E-01
+OR3A3	8.13E-01
+FAM151B	8.13E-01
+UBXN6	8.13E-01
+CHP2	8.13E-01
+C17orf47	8.13E-01
+LXN	8.13E-01
+MRPL46	8.13E-01
+RTP4	8.13E-01
+HPS1	8.13E-01
+NDUFV2	8.14E-01
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+SPP2	8.14E-01
+SLC22A8	8.14E-01
+PAAF1	8.14E-01
+ZNF836	8.14E-01
+SNX20	8.14E-01
+LTA4H	8.14E-01
+TACR2	8.14E-01
+ESF1	8.14E-01
+AARS2	8.14E-01
+C22orf43	8.14E-01
+QSOX1	8.14E-01
+UGGT1	8.14E-01
+NEDD1	8.14E-01
+METTL4	8.15E-01
+WFDC1	8.15E-01
+MTERFD2	8.15E-01
+MRPL44	8.15E-01
+LRWD1	8.15E-01
+DNAJC15	8.15E-01
+MTHFD1L	8.15E-01
+OR9Q2	8.15E-01
+ELN	8.15E-01
+NPM2	8.15E-01
+DNAJA4	8.15E-01
+DYNC1I1	8.15E-01
+WDR3	8.15E-01
+KLF11	8.15E-01
+ZNF454	8.16E-01
+ACSM5	8.16E-01
+NAPSA	8.16E-01
+EPN3	8.16E-01
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+NECAB2	8.16E-01
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+NAT2	8.16E-01
+TIRAP	8.16E-01
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+PDE6C	8.16E-01
+PRG3	8.16E-01
+IMP4	8.16E-01
+SYT12	8.16E-01
+RRP8	8.16E-01
+MOXD1	8.17E-01
+VPS16	8.17E-01
+ADAM30	8.17E-01
+PTGR2	8.17E-01
+PIWIL2	8.17E-01
+NOS3	8.17E-01
+S100A4	8.17E-01
+CENPQ	8.17E-01
+NQO2	8.17E-01
+S100A13	8.17E-01
+ZNF23	8.17E-01
+MTFMT	8.17E-01
+REP15	8.17E-01
+TBPL2	8.17E-01
+DAK	8.17E-01
+DNAJB2	8.18E-01
+MR1	8.18E-01
+ZNF416	8.18E-01
+RHPN1	8.18E-01
+TMEM144	8.18E-01
+UFSP2	8.18E-01
+DPH1	8.18E-01
+CALCOCO2	8.18E-01
+FANCE	8.18E-01
+OR12D3	8.18E-01
+HAO1	8.18E-01
+ATP4B	8.18E-01
+ZNF138	8.18E-01
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+KANK4	8.19E-01
+TMC1	8.19E-01
+RIMS1	8.19E-01
+PCM1	8.19E-01
+AADAC	8.19E-01
+CLEC12A	8.19E-01
+BTBD1	8.19E-01
+NAGK	8.19E-01
+C19orf18	8.19E-01
+FBXO39	8.19E-01
+NME6	8.19E-01
+ELOVL2	8.19E-01
+GPR142	8.19E-01
+OR4L1	8.19E-01
+GTF3C3	8.19E-01
+TTLL9	8.20E-01
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+WDR4	8.20E-01
+APOA1BP	8.20E-01
+LMAN2L	8.20E-01
+GABPB2	8.20E-01
+C16orf78	8.20E-01
+RSPH6A	8.20E-01
+TOP2B	8.20E-01
+LCN1	8.20E-01
+SYT8	8.20E-01
+NCR3	8.20E-01
+CST11	8.20E-01
+SLITRK6	8.20E-01
+TTC39A	8.21E-01
+PDCL3	8.21E-01
+GYPC	8.21E-01
+NUFIP1	8.21E-01
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+ANKRD1	8.21E-01
+CDK5RAP3	8.21E-01
+FAM109B	8.21E-01
+ELF5	8.21E-01
+GLO1	8.21E-01
+SPHK1	8.21E-01
+CR1L	8.21E-01
+AGTR1	8.21E-01
+NT5DC1	8.21E-01
+P4HA3	8.21E-01
+HAPLN3	8.22E-01
+ACP6	8.22E-01
+SHMT2	8.22E-01
+GGT5	8.22E-01
+LRRC48	8.22E-01
+PNPLA6	8.22E-01
+ACE	8.22E-01
+VPS33B	8.22E-01
+SLC43A1	8.22E-01
+DHX34	8.22E-01
+C1orf127	8.22E-01
+ULK2	8.22E-01
+ACBD4	8.22E-01
+PIWIL1	8.22E-01
+CD3G	8.23E-01
+VWCE	8.23E-01
+GART	8.23E-01
+OTOP2	8.23E-01
+C8G	8.23E-01
+ZNF562	8.23E-01
+OR1S2	8.23E-01
+PIGK	8.23E-01
+DISC1	8.23E-01
+MGMT	8.23E-01
+ICAM4	8.23E-01
+ZNF765	8.23E-01
+SLC4A1AP	8.23E-01
+PON2	8.23E-01
+SKA3	8.23E-01
+GYLTL1B	8.24E-01
+ALDH8A1	8.24E-01
+TM4SF20	8.24E-01
+CYP2F1	8.24E-01
+GHRHR	8.24E-01
+OR52K1	8.24E-01
+OR7E24	8.24E-01
+ZNF136	8.24E-01
+GLP2R	8.24E-01
+SHISA5	8.24E-01
+OR8K5	8.24E-01
+PROM2	8.24E-01
+SLC35D2	8.24E-01
+RBKS	8.24E-01
+CHID1	8.25E-01
+OR9A2	8.25E-01
+ZNF616	8.25E-01
+NDUFA6	8.25E-01
+CPA1	8.25E-01
+CASP14	8.25E-01
+RAP1GDS1	8.25E-01
+PCSK5	8.25E-01
+TAS2R41	8.25E-01
+GGT6	8.25E-01
+CNPY4	8.25E-01
+SIGLEC8	8.25E-01
+ADAMTS18	8.25E-01
+OR2D3	8.25E-01
+OR5T1	8.25E-01
+CWH43	8.26E-01
+MYBPH	8.26E-01
+DDX43	8.26E-01
+PENK	8.26E-01
+TXNDC2	8.26E-01
+ANXA1	8.26E-01
+GMCL1	8.26E-01
+TNFAIP6	8.26E-01
+ADH5	8.26E-01
+PGPEP1L	8.26E-01
+ZNF776	8.26E-01
+HIST1H1T	8.26E-01
+GALM	8.26E-01
+C12orf42	8.26E-01
+CARD9	8.27E-01
+FAM83D	8.27E-01
+GSTM3	8.27E-01
+CLCA1	8.27E-01
+LRRFIP1	8.27E-01
+PPIL4	8.27E-01
+TAF6	8.27E-01
+UPK2	8.27E-01
+EXOSC7	8.27E-01
+ZNF230	8.27E-01
+LNX1	8.27E-01
+ZNF714	8.27E-01
+TAS2R9	8.27E-01
+COG4	8.27E-01
+FAM3C	8.27E-01
+CFHR1	8.28E-01
+OR8K3	8.28E-01
+SLC39A7	8.28E-01
+RGS13	8.28E-01
+APOBEC1	8.28E-01
+UGT2A3	8.28E-01
+DEFB126	8.28E-01
+SYNGR4	8.28E-01
+RFPL3	8.28E-01
+C9orf117	8.28E-01
+HAAO	8.28E-01
+ZNF665	8.28E-01
+WDR73	8.28E-01
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+CIB4	8.30E-01
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+CEP120	9.54E-01
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+CES1	9.54E-01
+TMEM63A	9.54E-01
+TCP11L2	9.54E-01
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+BVES	9.55E-01
+ZNF559	9.55E-01
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+PTGR1	9.55E-01
+ALPK1	9.55E-01
+TCN1	9.55E-01
+HIBCH	9.55E-01
+PLTP	9.55E-01
+C5orf34	9.55E-01
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+OGFOD1	9.55E-01
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+TRIB3	9.56E-01
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+HRG	9.56E-01
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+KIAA1377	9.58E-01
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+C1orf27	9.63E-01
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+TC2N	9.96E-01
+ANO6	9.96E-01
+SCEL	9.96E-01
+PMFBP1	9.96E-01
+CASP5	9.96E-01
+NAT1	9.96E-01
+SLC44A3	9.96E-01
+LGALS8	9.96E-01
+DNAH7	9.96E-01
+HLA-B	9.96E-01
+ODF2L	9.96E-01
+LRRIQ1	9.97E-01
+MCM8	9.97E-01
+ZDHHC4	9.97E-01
+TCHP	9.97E-01
+NUDT1	9.97E-01
+EFCAB5	9.97E-01
+UGGT2	9.97E-01
+CD55	9.97E-01
+CRYZ	9.97E-01
+SPINK5	9.97E-01
+IGSF10	9.97E-01
+C9orf84	9.97E-01
+DNAH14	9.97E-01
+FMO3	9.97E-01
+KNTC1	9.98E-01
+DYNC2H1	9.98E-01
+ECD	9.98E-01
+KCNMB3	9.98E-01
+HAP1	9.98E-01
+DENND4A	9.98E-01
+LY75	9.98E-01
+ZNF83	9.98E-01
+HMMR	9.98E-01
+MPDZ	9.98E-01
+AHI1	9.98E-01
+TET2	9.98E-01
+SLC30A8	9.98E-01
+BANK1	9.98E-01
+MUC16	9.98E-01
+ERAP1	9.99E-01
+DMBT1	9.99E-01
+PCK2	9.99E-01
+SEC16A	9.99E-01
+FAM198B	9.99E-01
+CMYA5	9.99E-01
+PLA2R1	9.99E-01
+ELMOD3	9.99E-01
+MCTP2	9.99E-01
+IL32	9.99E-01
+HLA-DRB5	9.99E-01
+CCDC77	9.99E-01
+VRK2	9.99E-01
+CRIPAK	9.99E-01
+PLA2G7	1.00E+00
+GPR113	1.00E+00
+CD109	1.00E+00
+PLB1	1.00E+00
+CEP63	1.00E+00
+THADA	1.00E+00
+CLTCL1	1.00E+00
+HLA-DRB1	1.00E+00

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/LocalID.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,344 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ LocalID
+
+=head1 SYNOPSIS
+
+ mv LocalID.pm ~/.vep/Plugins
+
+ ## first run create database
+
+ # EITHER create from Ensembl variation database
+ # VERY slow but includes variant synonyms, if not required see next command
+ ./vep -i variant_ids.txt --plugin LocalID,create_db=1 -safe
+
+ # OR create from cache directory
+ # faster but does not include synonyms
+ # parameter passed to from_cache may be full path to cache e.g. $HOME/.vep/homo_sapiens/88_GRCh38
+ # cache may be tabix converted or in default state (http://www.ensembl.org/info/docs/tools/vep/script/vep_cache.html#convert)
+ ./vep -i variant_ids.txt --plugin LocalID,create_db=1,from_cache=1 -safe
+
+ # subsequent runs
+ ./vep -i variant_ids.txt --plugin LocalID
+
+ # db file can be specified with db=[file]
+ # default file name is $HOME/.vep/[species]_[version]_[assembly].variant_ids.sqlite3
+ ./vep -i variant_ids.txt --plugin LocalID,db=my_db_file.txt
+
+=head1 DESCRIPTION
+
+ The LocalID plugin allows you to use variant IDs as input without making a database connection.
+
+ Requires sqlite3.
+ 
+ A local sqlite3 database is used to look up variant IDs; this is generated either from Ensembl's
+ public database (very slow, but includes synonyms), or from a VEP cache file (faster, excludes
+ synonyms).
+
+ NB this plugin is NOT compatible with the ensembl-tools variant_effect_predictor.pl version of VEP.
+
+=cut
+
+package LocalID;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+use Bio::EnsEMBL::VEP::Parser::ID;
+use Bio::EnsEMBL::VEP::Constants;
+use Bio::EnsEMBL::VEP::Utils qw(get_compressed_filehandle);
+
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+
+  my $param_hash = $self->params_to_hash();
+  my $config     = $self->{config};
+  my $species    = $config->{species} || 'homo_sapiens';
+  my $db;
+
+  unless($db = $param_hash->{db}) {
+    my $version =
+      $config->{db_version} ||
+      $config->{cache_version} ||
+      $Bio::EnsEMBL::VEP::Constants::VEP_VERSION ||
+      'Bio::EnsEMBL::Registry'->software_version ||
+      undef;
+    my $assembly = $config->{assembly};
+    my $dir = $param_hash->{dir} || $config->{dir};
+
+    die("ERROR: Unable to determine software version - if using --offline, add --cache_version [version] or add the ID database name to your --plugin string as \"db=[file]\"\n") unless $version;
+    die("ERROR: Unable to determine assembly version - if using --offline, add --assembly [version] or add the ID database name to your --plugin string as \"db=[file]\"\n") unless $assembly;
+    $db = sprintf("%s/%s_%i_%s.variant_ids.sqlite3", $dir, $species, $version, $assembly);
+  }  
+
+  # create DB?
+  $self->create_db($db, $species, $param_hash) if $param_hash->{create_db};
+
+  die("ERROR: DB file $db not found - you need to download or create it first, see documentation in plugin file\n") unless -e $db;
+
+  $self->config->{_localid_db_file} = $db;
+
+  return $self;
+}
+
+sub create_db {
+  my ($self, $db, $species, $param_hash) = @_;
+
+  # requites sqlite3 command line tool
+  die("ERROR: sqlite3 command not found in path\n") unless `which sqlite3` =~ /\/sqlite3/;
+
+  my $config = $self->{config};
+
+  die("ERROR: DB file $db already exists - remove and re-run to overwrite\n") if -e $db;
+
+  print STDERR "## LocalID plugin\n # Creating database of variant IDs - this may take some time\n" unless $config->{quiet};
+
+  my $tmpfile = "$db.tmp$$";
+  open my $tmp_handle, ">$tmpfile" or die "ERROR: Unable to write to $tmpfile\n";
+
+  if(my $cache_dir = $param_hash->{from_cache}) {
+
+    # attempt to interpret cache dir from command line opts
+    if($cache_dir eq '1') {
+      my $version =
+        $config->{cache_version} ||
+        $config->{db_version} ||
+        $Bio::EnsEMBL::VEP::Constants::VEP_VERSION ||
+        ($config->{reg} ? $config->{reg}->software_version : undef);
+      my $assembly = $config->{assembly};
+      my $dir = $config->{dir_cache} || $config->{dir};
+
+      $cache_dir = "$dir\/$species\/$version\_$assembly";
+    }
+
+    print STDERR " # attempting to create from $cache_dir\n" unless $config->{quiet};
+    $self->_tmp_file_from_cache($cache_dir, $tmp_handle);
+  }
+  else {
+    print STDERR " # attempting to create from variation database for $species\n" unless $config->{quiet};
+    $self->_tmp_file_from_var_db($species, $tmp_handle);
+  }
+
+  close $tmp_handle;
+
+  # create database
+  my $dbh = DBI->connect("dbi:SQLite:dbname=$db","","");
+  $dbh->do("CREATE TABLE ids(id, chr, start, end, alleles, strand)");
+
+  # load tmp file into table
+  print STDERR " # loading database\n" unless $config->{quiet};
+  my $cmd = qq{sqlite3 $db '.import $tmpfile ids'};
+  `$cmd 2>&1` and die("ERROR: Failed to import $tmpfile to $db\n");
+  unlink($tmpfile);
+
+  # index
+  print STDERR " # indexing database\n" unless $config->{quiet};
+  $dbh->do("CREATE INDEX id_idx ON ids(id)");
+
+  print STDERR " # successfully built database $db\n" unless $config->{quiet};
+}
+
+sub _tmp_file_from_cache {
+  my ($self, $cache_dir, $tmp_handle) = @_;
+  my $config = $self->{config};
+
+  die("ERROR: Cache dir $cache_dir not found or not a directory\n") unless -d $cache_dir;
+
+  # read info
+  open INFO, $cache_dir.'/info.txt' or die("ERROR: No info.txt file found in $cache_dir\n");
+
+  my %cols;
+  while(<INFO>) {
+    next unless /^variation_cols/;
+    chomp;
+    my @tmp_cols = split(',', (split("\t", $_))[1]);
+    $cols{$tmp_cols[$_]} = $_ for 0..$#tmp_cols;
+    last;
+  }
+  close INFO;
+
+  # get all chromosome dirs
+  opendir DIR, $cache_dir or die("ERROR: Could not read dir $cache_dir\n");
+  my @chrs = grep {-d $cache_dir.'/'.$_ && !/^\./} readdir DIR;
+  closedir DIR;
+
+  foreach my $chr(@chrs) {
+    opendir CHR, $cache_dir.'/'.$chr;
+    my @all_files = grep {/var/ && !/\.(tb|cs)i$/} readdir CHR;
+    closedir CHR;
+
+    my @files = grep {/all_vars/} @all_files;
+    @files = @all_files unless @files;
+
+    foreach my $file(@files) {
+      my $fh = get_compressed_filehandle($cache_dir.'/'.$chr.'/'.$file, 1);
+
+      my $delim;
+
+      while(<$fh>) {
+        unless($delim) {
+          $delim = /\t/ ? "\t" : " ";
+        }
+
+        chomp;
+        my @split = map {($_ || '') eq '.' ? undef : $_} split($delim);
+
+        # id, chr, start, end, alleles, strand
+        print $tmp_handle join("|",
+          $split[$cols{variation_name}],
+          $chr,
+          $split[$cols{start}],
+          $split[$cols{end}] || $split[$cols{start}],
+          $split[$cols{allele_string}] || '',
+          $split[$cols{strand}] || 1,
+        )."\n";
+      }
+
+      close $fh;
+    }
+  }
+}
+
+sub _tmp_file_from_var_db {
+  my ($self, $species, $tmp_handle) = @_;
+  my $config = $self->{config};
+
+  my $var_dbc = Bio::EnsEMBL::Registry->get_adaptor($species, 'variation', 'variation')->db->dbc;
+
+  my $mysql = $var_dbc->prepare(qq{
+    SELECT v.name, s.name, vf.seq_region_start, vf.seq_region_end, vf.allele_string, vf.seq_region_strand
+    FROM variation v, variation_feature vf, seq_region s
+    WHERE v.variation_id = vf.variation_id
+    AND vf.seq_region_id = s.seq_region_id
+  }, {mysql_use_result => 1});
+
+  my ($i, $c, $s, $e, $a, $d);
+  $mysql->execute();
+  $mysql->bind_columns(\$i, \$c, \$s, \$e, \$a, \$d);
+  print $tmp_handle join("|", ($i, $c, $s, $e, $a, $d))."\n" while $mysql->fetch();
+  $mysql->finish();
+
+  # do synonyms
+  print STDERR "Processing synonyms\n" unless $config->{quiet};
+  $mysql = $var_dbc->prepare(qq{
+    SELECT v.name, s.name, vf.seq_region_start, vf.seq_region_end, vf.allele_string, vf.seq_region_strand
+    FROM variation_synonym v, variation_feature vf, seq_region s
+    WHERE v.variation_id = vf.variation_id
+    AND vf.seq_region_id = s.seq_region_id
+  }, {mysql_use_result => 1});
+
+  $mysql->execute();
+  $mysql->bind_columns(\$i, \$c, \$s, \$e, \$a, \$d);
+  print $tmp_handle join("|", ($i, $c, $s, $e, $a, $d))."\n" while $mysql->fetch();
+  $mysql->finish();
+}
+
+sub run {
+  return {};
+}
+
+1;
+
+
+
+
+###########################################
+### Redefine methods in existing module ###
+###########################################
+
+package Bio::EnsEMBL::VEP::Parser::ID;
+
+no warnings qw(redefine);
+sub new {
+  my $caller = shift;
+  my $class = ref($caller) || $caller;
+  
+  my $self = $class->SUPER::new(@_);
+
+  return $self;
+}
+
+sub create_VariationFeatures {
+  my $self = shift;
+
+  my $parser = $self->parser;
+  $parser->next();
+
+  $self->skip_empty_lines();
+
+  return [] unless $parser->{record};
+
+  $self->line_number($self->line_number + 1);
+
+  my $id = $parser->get_value;
+
+  # remove whitespace
+  $id =~ s/\s+//g;
+
+  my $db  = $self->id_db;
+  my $sth = $self->{_id_sth} ||= $db->prepare("SELECT chr, start, end, alleles, strand FROM ids WHERE id = ?");
+  my $ad  = $self->{_var_ad} ||= $self->get_adaptor('variation', 'VariationFeature');
+
+  my @vfs;
+  my ($c, $s, $e, $a, $d);
+  $sth->execute($id);
+  $sth->bind_columns(\$c, \$s, \$e, \$a, \$d);
+
+  push @vfs, Bio::EnsEMBL::Variation::VariationFeature->new_fast({
+    start          => $s,
+    end            => $e,
+    allele_string  => $a,
+    strand         => $d,
+    map_weight     => 1,
+    adaptor        => $ad,
+    variation_name => $id,
+    chr            => $c,
+  }) while $sth->fetch;
+
+  $sth->finish();
+
+  return $self->post_process_vfs(\@vfs);
+}
+
+sub id_db {
+  my $self = shift;
+
+  unless(exists($self->{_id_db})) {
+    throw("ERROR: ID database not defined or detected - possible plugin compile failure\n") unless my $db = $self->config->{_params}->{_localid_db_file};
+    throw("ERROR: ID database file $db not found - you need to download or create it first, see documentation in plugin file\n") unless -e $db;
+    $self->{_id_db} = DBI->connect("dbi:SQLite:dbname=$db","","");
+  }
+
+  return $self->{_id_db};
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/MPC.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,135 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ MPC
+
+=head1 SYNOPSIS
+
+ mv MPC.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin MPC,fordist_constraint_official_mpc_values.txt.gz
+
+=head1 DESCRIPTION
+
+ A VEP plugin that retrieves MPC scores for variants from a tabix-indexed MPC data file.
+
+ MPC is a missense deleteriousness metric based on the analysis of genic regions
+ depleted of missense mutations in the Exome Agggregation Consortium (ExAC) data.
+
+ The MPC score is the product of work by Kaitlin Samocha ([e-mail]).
+ Publication currently in pre-print: Samocha et al bioRxiv 2017 (TBD)
+ 
+ The MPC score file is available to download from:
+
+ ftp://ftp.broadinstitute.org/pub/ExAC_release/release1/regional_missense_constraint/
+
+ The data are currently mapped to GRCh37 only. Not all transcripts are included; see
+ README in the above directory for exclusion criteria.
+ 
+=cut
+
+package MPC;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin);
+
+my %INCLUDE_SO = map {$_ => 1} qw(missense_variant stop_lost stop_gained start_lost);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+
+  $self->expand_left(0);
+  $self->expand_right(0);
+
+  $self->get_user_params();
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  return { MPC => 'MPC score' };
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  # only for missense variants
+  return {} unless grep {$INCLUDE_SO{$_->SO_term}} @{$tva->get_all_OverlapConsequences};
+  
+  my $vf = $tva->variation_feature;
+  
+  return {} unless $vf->{start} eq $vf->{end};
+  
+  # get allele, reverse comp if needed
+  my $allele = $tva->variation_feature_seq;
+  reverse_comp(\$allele) if $vf->{strand} < 0;
+  
+  return {} unless $allele =~ /^[ACGT]$/;
+  
+  # get transcript stable ID
+  my $tr_id = $tva->transcript->stable_id;
+
+  my ($res) = grep {
+    $_->{pos} == $vf->{start} &&
+    $_->{alt} eq $allele &&
+    $_->{tr}  eq $tr_id
+  } @{$self->get_data($vf->{chr}, $vf->{start}, $vf->{end})};
+
+  return $res ? { MPC => $res->{MPC} } : {};
+}
+
+sub parse_data {
+  my ($self, $line) = @_;
+
+  my @split = split /\t/, $line;
+
+  return {
+    pos => $split[1],
+    alt => $split[3],
+    tr  => $split[5],
+    MPC => $split[-1],
+  };
+}
+
+sub get_start {
+  return $_[1]->{pos};
+}
+
+sub get_end {
+  return $_[1]->{pos};
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/MTR.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,153 @@
+=head1 CONTACT
+
+  Slave Petrovski <[e-mail]>
+  Michael Silk <[e-mail]>
+
+=cut
+
+=head1 NAME
+
+  MTR (Missense Tolerance Ratio)
+
+=head1 SYNOPSIS
+
+  mv MTR.pm ~/.vep/Plugins
+  curl -O ftp://mtr-viewer.mdhs.unimelb.edu.au/pub/mtrflatfile_1.0.txt.gz
+  curl -O ftp://mtr-viewer.mdhs.unimelb.edu.au/pub/mtrflatfile_1.0.txt.gz.tbi
+  perl variant_effect_predictor.pl -i variations.vcf --plugin MTR,mtrflatfile_1.0.txt.gz
+
+=head1 DESCRIPTION
+
+A VEP plugin that retrieves Missense Tolerance Ratio (MTR) scores for
+variants from a tabix-indexed flat file.
+
+MTR scores quantify the amount of purifying selection acting
+specifically on missense variants in a given window of protein-coding
+sequence. It is estimated across a sliding window of 31 codons and uses
+observed standing variation data from the WES component of the Exome
+Aggregation Consortium Database (ExAC), version 2.0
+(http://gnomad.broadinstitute.org).
+
+Please cite the MTR publication alongside the VEP if you use this resource:
+http://genome.cshlp.org/content/27/10/1715
+
+The Bio::DB::HTS perl library or tabix utility must be installed in your path
+to use this plugin. MTR flat files can be downloaded from:
+ftp://mtr-viewer.mdhs.unimelb.edu.au/pub
+
+NB: Data are available for GRCh37 only
+
+=cut
+
+package MTR;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin);
+
+sub new {
+  my $class = shift;
+  my $self = $class->SUPER::new(@_);
+
+  # test tabix
+  die "ERROR: tabix does not seem to be in your path\n" unless `which tabix 2>&1` =~ /tabix$/;
+
+  # get MTR file
+  my $file = $self->params->[0];
+  $self->add_file($file);
+
+  # remote files?
+  if($file =~ /tp\:\/\//) {
+    my $remote_test = `tabix -f $file 1:1-1 2>&1`;
+    if($remote_test && $remote_test !~ /get_local_version/) {
+      die "$remote_test\nERROR: Could not find file or index file for remote annotation file $file\n";
+    }
+  }
+
+  # check files exist
+  else {
+    die "ERROR: MTR file $file not found\n" unless -e $file;
+    die "ERROR: Tabix index file $file\.tbi not found - perhaps you need to create it first?\n" unless -e $file.'.tbi';
+  }
+
+  # get headers and store on self
+  open HEAD, "tabix -fh $file 1:1-1 2>&1 | ";
+  while(<HEAD>) {
+    next unless /^\#/;
+    chomp;
+    $self->{headers} = [split];
+  }
+  close HEAD;
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub variation_feature_types {
+  return ['VariationFeature'];
+}
+
+sub get_header_info {
+  my $self = shift;
+  return {
+	  MTR         => 'MTR score',
+	  FDR         => 'MTR false discovery rate adjusted binomial exact test.',
+	  MTR_centile => 'MTR gene-specific percentile'
+	 }
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  my $vf = $tva->variation_feature;
+
+  # get allele, reverse comp if needed
+  my $allele = $tva->variation_feature_seq;
+  reverse_comp(\$allele) if $vf->{strand} < 0;
+
+  return {} unless $allele =~ /^[ACGT]$/;
+
+  my $tr_id = $tva->transcript->stable_id;
+
+  # data is written by pos, allele, transcript ID (feature)
+  # grep lines read in matched on position so that they also are matched on allele and transcript ID
+  my ($res) = grep {
+    $_->{Genomic_position} eq $vf->{start} &&
+    $_->{Genomic_position} eq $vf->{end} &&
+    $_->{alt}              eq $allele &&
+    $_->{Feature}          eq $tr_id
+  } @{$self->get_data($vf->{chr}, $vf->{start}, $vf->{end})};
+
+  # return only the keys defined by get_header_info()
+  return $res ? { map {$_ => $res->{$_}} grep {defined($res->{$_}) && $res->{$_} ne '.'} keys %{$self->get_header_info} } : {};
+}
+
+sub parse_data {
+  my ($self, $line) = @_;
+
+  $line =~ s/\r$//g;
+
+  my @split = split /\t/, $line;
+  
+  # parse data into hash of col names and values
+  my %data = map {$self->{headers}->[$_] => $split[$_]} (0..(scalar @{$self->{headers}} - 1));
+
+  return \%data;
+}
+
+sub get_start {  
+  return $_[1]->{'Genomic_position'};
+}
+
+sub get_end {
+  return $_[1]->{'Genomic_position'};
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/MaxEntScan.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,895 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ MaxEntScan
+
+=head1 SYNOPSIS
+
+ mv MaxEntScan.pm ~/.vep/Plugins
+ ./vep -i variants.vcf --plugin MaxEntScan,/path/to/maxentscan/fordownload
+ ./vep -i variants.vcf --plugin MaxEntScan,/path/to/maxentscan/fordownload,SWA,NCSS
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+ runs MaxEntScan (http://genes.mit.edu/burgelab/maxent/Xmaxentscan_scoreseq.html)
+ to get splice site predictions.
+
+ The plugin copies most of the code verbatim from the score5.pl and score3.pl
+ scripts provided in the MaxEntScan download. To run the plugin you must get and
+ unpack the archive from http://genes.mit.edu/burgelab/maxent/download/; the path
+ to this unpacked directory is then the param you pass to the --plugin flag.
+
+ The plugin executes the logic from one of the scripts depending on which
+ splice region the variant overlaps:
+
+ score5.pl : last 3 bases of exon    --> first 6 bases of intron
+ score3.pl : last 20 bases of intron --> first 3 bases of exon
+
+ The plugin reports the reference, alternate and difference (REF - ALT) maximum
+ entropy scores.
+
+ If 'SWA' is specified as a command-line argument, a sliding window algorithm
+ is applied to subsequences containing the reference and alternate alleles to
+ identify k-mers with the highest donor and acceptor splice site scores. To assess
+ the impact of variants, reference comparison scores are also provided. For SNVs,
+ the comparison scores are derived from sequence in the same frame as the highest
+ scoring k-mers containing the alternate allele. For all other variants, the
+ comparison scores are derived from the highest scoring k-mers containing the
+ reference allele. The difference between the reference comparison and alternate
+ scores (SWA_REF_COMP - SWA_ALT) are also provided.
+
+ If 'NCSS' is specified as a command-line argument, scores for the nearest
+ upstream and downstream canonical splice sites are also included.
+
+ By default, only scores are reported. Add 'verbose' to the list of command-
+ line arguments to include the sequence output associated with those scores.
+
+=cut
+
+package MaxEntScan;
+
+use strict;
+use warnings;
+
+use Digest::MD5 qw(md5_hex);
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+use Bio::EnsEMBL::Variation::Utils::VariationEffect qw(overlap);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+# how many seq/score pairs to cache in memory
+our $CACHE_SIZE = 50;
+
+sub new {
+  my $class = shift;
+
+  my $self = $class->SUPER::new(@_);
+  
+  # we need sequence, so no offline mode unless we have FASTA
+  die("ERROR: cannot function in offline mode without a FASTA file\n") if $self->{config}->{offline} && !$self->{config}->{fasta};
+
+  my $params = $self->params;
+
+  my $dir = shift @$params;
+  die("ERROR: MaxEntScan directory not specified\n") unless $dir;
+  die("ERROR: MaxEntScan directory not found\n") unless -d $dir;
+  $self->{_dir} = $dir;
+
+  ## setup from score5.pl
+  $self->{'score5_me2x5'} = $self->score5_makescorematrix($dir.'/me2x5');
+  $self->{'score5_seq'}   = $self->score5_makesequencematrix($dir.'/splicemodels/splice5sequences');
+
+  ## setup from score3.pl
+  $self->{'score3_metables'} = $self->score3_makemaxentscores;
+
+  my %opts = map { $_ => undef } @$params;
+
+  $self->{'run_SWA'} = 1 if exists $opts{'SWA'};
+  $self->{'run_NCSS'} = 1 if exists $opts{'NCSS'};
+
+  $self->{'verbose'} = 1 if exists $opts{'verbose'};
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  my $self = shift;
+
+  my $v = $self->{'verbose'};
+  my $headers = $self->get_MES_header_info($v);
+
+  if ($self->{'run_SWA'}) {
+    my $swa_headers = $self->get_SWA_header_info($v);
+    $headers = {%$headers, %$swa_headers};
+  }
+
+  if ($self->{'run_NCSS'}) {
+    my $ncss_headers = $self->get_NCSS_header_info($v);
+    $headers = {%$headers, %$ncss_headers};
+  }
+
+  return $headers;
+}
+
+sub get_MES_header_info {
+  my ($self, $verbose) = @_;
+
+  my $headers = {
+    MaxEntScan_ref => "MaxEntScan reference sequence score",
+    MaxEntScan_alt => "MaxEntScan alternate sequence score",
+    MaxEntScan_diff => "MaxEntScan score difference",
+  };
+
+  if ($verbose) {
+
+    $headers->{'MaxEntScan_ref_seq'} = "MaxEntScan reference sequence";
+    $headers->{'MaxEntScan_alt_seq'} = "MaxEntScan alternate sequence";
+  }
+
+  return $headers;
+}
+
+sub get_SWA_header_info {
+  my ($self, $verbose) = @_;
+
+  my $headers = {
+    "MES-SWA_donor_ref" => "Highest splice donor reference sequence score",
+    "MES-SWA_donor_alt" => "Highest splice donor alternate sequence score",
+    "MES-SWA_donor_ref_comp" => "Donor reference comparison sequence score",
+    "MES-SWA_donor_diff" => "Difference between the donor reference comparison and alternate sequence scores",
+
+    "MES-SWA_acceptor_ref" => "Highest splice acceptor reference sequence score",
+    "MES-SWA_acceptor_alt" => "Highest splice acceptor alternate sequence score",
+    "MES-SWA_acceptor_ref_comp" => "Acceptor reference comparison sequence score",
+    "MES-SWA_acceptor_diff" => "Difference between the acceptor reference comparison and alternate sequence scores",
+  };
+
+  if ($verbose) {
+
+    $headers->{'MES-SWA_donor_ref_seq'} = "Highest splice donor reference sequence";
+    $headers->{'MES-SWA_donor_ref_frame'} = "Position of the highest splice donor reference sequence";
+    $headers->{'MES-SWA_donor_ref_context'} = "Selected donor sequence context containing the reference allele";
+    $headers->{'MES-SWA_donor_alt_seq'} = "Highest splice donor alternate sequence";
+    $headers->{'MES-SWA_donor_alt_frame'} = "Position of the highest splice donor alternate sequence";
+    $headers->{'MES-SWA_donor_alt_context'} = "Selected donor sequence context containing the alternate allele";
+    $headers->{'MES-SWA_donor_ref_comp_seq'} = "Donor reference comparison sequence";
+
+    $headers->{'MES-SWA_acceptor_ref_seq'} = "Highest splice acceptor reference sequence";
+    $headers->{'MES-SWA_acceptor_ref_frame'} = "Position of the highest splice acceptor reference sequence";
+    $headers->{'MES-SWA_acceptor_ref_context'} = "Selected acceptor sequence context containing the reference allele";
+    $headers->{'MES-SWA_acceptor_alt_seq'} = "Highest splice acceptor alternate sequence";
+    $headers->{'MES-SWA_acceptor_alt_frame'} = "Position of the highest splice acceptor alternate sequence";
+    $headers->{'MES-SWA_acceptor_alt_context'} = "Selected acceptor sequence context containing the alternate allele";
+    $headers->{'MES-SWA_acceptor_ref_comp_seq'} = "Acceptor reference comparison sequence";
+  }
+
+  return $headers;
+}
+
+sub get_NCSS_header_info {
+  my ($self, $verbose) = @_;
+
+  my $headers = {
+    "MES-NCSS_upstream_acceptor" => "Nearest upstream canonical splice acceptor sequence score",
+    "MES-NCSS_upstream_donor" => "Nearest upstream canonical splice donor sequence score",
+
+    "MES-NCSS_downstream_acceptor" => "Nearest downstream canonical splice acceptor sequence score",
+    "MES-NCSS_downstream_donor" => "Nearest downstream canonical splice donor sequence score",
+  };
+
+  if ($verbose) {
+
+    $headers->{'MES-NCSS_upstream_acceptor_seq'} = "Nearest upstream canonical splice acceptor sequence";
+    $headers->{'MES-NCSS_upstream_donor_seq'} = "Nearest upstream canonical splice donor sequence";
+
+    $headers->{'MES-NCSS_downstream_acceptor_seq'} = "Nearest downstream canonical splice acceptor sequence";
+    $headers->{'MES-NCSS_downstream_donor_seq'} = "Nearest downstream canonical splice donor sequence";
+  }
+
+  return $headers;
+}
+
+sub run {
+  my ($self, $tva) = @_;
+
+  my $seq_headers = $self->get_MES_header_info();
+  my $results = $self->run_MES($tva);
+
+  if ($self->{'run_SWA'}) {
+    my $swa_seq_headers = $self->get_SWA_header_info();
+    $seq_headers = {%$seq_headers, %$swa_seq_headers};
+    my $swa_results = $self->run_SWA($tva);
+    $results = {%$results, %$swa_results};
+  }
+
+  if ($self->{'run_NCSS'}) {
+    my $ncss_seq_headers = $self->get_NCSS_header_info();
+    $seq_headers = {%$seq_headers, %$ncss_seq_headers};
+    my $ncss_results = $self->run_NCSS($tva);
+    $results = {%$results, %$ncss_results};
+  }
+
+  my %data;
+
+  # add the scores
+  my @scores = grep { exists $results->{$_} } keys %$seq_headers;
+  @data{@scores} = map { sprintf('%.3f', $_) } @{$results}{@scores};
+
+  if ($self->{'verbose'}) {
+    # add any remaining results
+    my @non_scores = grep { ! exists $data{$_} } keys %$results;
+    @data{@non_scores} = @{$results}{@non_scores};
+  }
+
+  return \%data;
+}
+
+sub run_MES {
+  my ($self, $tva) = @_;
+
+  my $vf = $tva->variation_feature;
+  return {} unless $vf->{start} == $vf->{end} && $tva->feature_seq =~ /^[ACGT]$/;
+
+  my $tv = $tva->transcript_variation;
+  my $tr = $tva->transcript;
+  my $tr_strand = $tr->strand;
+  my ($vf_start, $vf_end) = ($vf->start, $vf->end);
+
+  # use _overlapped_introns() method from BaseTranscriptVariation
+  # this will use an interval tree if available for superfast lookup of overlapping introns
+  # we have to expand the search space around $vf because we're looking for the splice region not the intron per se
+  foreach my $intron(@{$tv->_overlapped_introns($vf_start - 21, $vf_end + 21)}) {
+    
+    # get coords depending on strand
+    # MaxEntScan does different predictions for 5 and 3 prime
+    # and we need to feed it different bits of sequence for each
+    #
+    # 5prime, 3 bases of exon, 6 bases of intron:
+    # ===------
+    #
+    # 3prime, 20 bases of intron, 3 bases of exon
+    # --------------------===
+
+    my ($five_start, $five_end, $three_start, $three_end);
+
+    if($tr_strand > 0) {
+      ($five_start, $five_end)   = ($intron->start - 3, $intron->start + 5);
+      ($three_start, $three_end) = ($intron->end - 19, $intron->end + 3);
+    }
+
+    else {
+      ($five_start, $five_end)   = ($intron->end - 5, $intron->end + 3);
+      ($three_start, $three_end) = ($intron->start - 3, $intron->start + 19);
+    }
+
+    if(overlap($vf->start, $vf->end, $five_start, $five_end)) {
+      my ($ref_seq, $alt_seq) = @{$self->get_seqs($tva, $five_start, $five_end)};
+
+      return {} unless defined($ref_seq) && $ref_seq =~ /^[ACGT]+$/;
+      return {} unless defined($alt_seq) && $alt_seq =~ /^[ACGT]+$/;
+
+      my $ref_score = $self->score5($ref_seq);
+      my $alt_score = $self->score5($alt_seq);
+
+      return {
+        MaxEntScan_ref => $ref_score,
+        MaxEntScan_ref_seq => $ref_seq,
+        MaxEntScan_alt => $alt_score,
+        MaxEntScan_alt_seq => $alt_seq,
+        MaxEntScan_diff => $ref_score - $alt_score,
+      }
+    }
+
+    if(overlap($vf->start, $vf->end, $three_start, $three_end)) {
+      my ($ref_seq, $alt_seq) = @{$self->get_seqs($tva, $three_start, $three_end)};
+
+      return {} unless defined($ref_seq) && $ref_seq =~ /^[ACGT]+$/;
+      return {} unless defined($alt_seq) && $alt_seq =~ /^[ACGT]+$/;
+
+      my $ref_score = $self->score3($ref_seq);
+      my $alt_score = $self->score3($alt_seq);
+
+      return {
+        MaxEntScan_ref => $ref_score,
+        MaxEntScan_ref_seq => $ref_seq,
+        MaxEntScan_alt => $alt_score,
+        MaxEntScan_alt_seq => $alt_seq,
+        MaxEntScan_diff => $ref_score - $alt_score,
+      }
+    }
+  }
+
+  return {};
+}
+
+sub run_SWA {
+  my ($self, $tva) = @_;
+
+  my $vf = $tva->variation_feature;
+
+  my %results;
+
+  # get the donor reference and alternate sequence contexts
+  my ($donor_ref_context, $donor_alt_context) = @{$self->get_seqs($tva, $vf->start - 8, $vf->end + 8)};
+
+  if (defined($donor_ref_context)) {
+    $results{'MES-SWA_donor_ref_context'} = $donor_ref_context;
+
+    if ($donor_ref_context  =~ /^[ACGT]+$/) {
+      my ($seq, $frame, $score) = @{$self->get_max_donor($donor_ref_context)};
+      $results{'MES-SWA_donor_ref_seq'} = $seq;
+      $results{'MES-SWA_donor_ref_frame'} = $frame;
+      $results{'MES-SWA_donor_ref'} = $score;
+    }
+  }
+
+  if (defined($donor_alt_context)) {
+    $results{'MES-SWA_donor_alt_context'} = $donor_alt_context;
+
+    if ($donor_alt_context  =~ /^[ACGT]+$/) {
+      my ($seq, $frame, $score) = @{$self->get_max_donor($donor_alt_context)};
+      $results{'MES-SWA_donor_alt_seq'} = $seq;
+      $results{'MES-SWA_donor_alt_frame'} = $frame;
+      $results{'MES-SWA_donor_alt'} = $score;
+
+      if (defined(my $ref_comp_seq = $results{'MES-SWA_donor_ref_seq'})) {
+
+        if ($vf->{start} == $vf->{end} && $tva->feature_seq =~ /^[ACGT]$/) {
+          # for SNVs, compare to the same frame as the highest scoring ALT k-mer
+          $ref_comp_seq = substr($donor_ref_context, $frame - 1, 9);
+        }
+
+        $results{'MES-SWA_donor_ref_comp_seq'} = $ref_comp_seq;
+        $results{'MES-SWA_donor_ref_comp'} = $self->score5($ref_comp_seq);
+
+        $results{'MES-SWA_donor_diff'} = $results{'MES-SWA_donor_ref_comp'} - $score;
+      }
+    }
+  }
+
+  # get the acceptor reference and alternate sequence contexts
+  my ($acceptor_ref_context, $acceptor_alt_context) = @{$self->get_seqs($tva, $vf->start - 22, $vf->end + 22)};
+
+  if (defined($acceptor_ref_context)) {
+    $results{'MES-SWA_acceptor_ref_context'} = $acceptor_ref_context;
+
+    if ($acceptor_ref_context  =~ /^[ACGT]+$/) {
+      my ($seq, $frame, $score) = @{$self->get_max_acceptor($acceptor_ref_context)};
+      $results{'MES-SWA_acceptor_ref_seq'} = $seq;
+      $results{'MES-SWA_acceptor_ref_frame'} = $frame;
+      $results{'MES-SWA_acceptor_ref'} = $score;
+    }
+  }
+
+  if (defined($acceptor_alt_context)) {
+    $results{'MES-SWA_acceptor_alt_context'} = $acceptor_alt_context;
+
+    if ($acceptor_alt_context  =~ /^[ACGT]+$/) {
+      my ($seq, $frame, $score) = @{$self->get_max_acceptor($acceptor_alt_context)};
+      $results{'MES-SWA_acceptor_alt_seq'} = $seq;
+      $results{'MES-SWA_acceptor_alt_frame'} = $frame;
+      $results{'MES-SWA_acceptor_alt'} = $score;
+
+      if (defined(my $ref_comp_seq = $results{'MES-SWA_acceptor_ref_seq'})) {
+
+        if ($vf->{start} == $vf->{end} && $tva->feature_seq =~ /^[ACGT]$/) {
+          # for SNVs, compare to the same frame as the highest scoring ALT k-mer
+          $ref_comp_seq = substr($acceptor_ref_context, $frame - 1, 23);
+        }
+
+        $results{'MES-SWA_acceptor_ref_comp_seq'} = $ref_comp_seq;
+        $results{'MES-SWA_acceptor_ref_comp'} = $self->score3($ref_comp_seq);
+
+        $results{'MES-SWA_acceptor_diff'} = $results{'MES-SWA_acceptor_ref_comp'} - $score;
+      }
+    }
+  }
+
+  return \%results;
+}
+
+sub run_NCSS {
+  my ($self, $tva) = @_;
+
+  my $tv = $tva->transcript_variation;
+  my $tr = $tva->transcript;
+
+  my %results;
+
+  if ($tv->intron_number) {
+
+    my ($intron_numbers, $total_introns) = split(/\//, $tv->intron_number);
+    my $intron_number = (split(/-/, $intron_numbers))[0];
+
+    my $introns = $tr->get_all_Introns;
+
+    my $intron_idx = $intron_number - 1;
+    my $intron = $introns->[$intron_idx];
+
+    if (defined(my $seq = $self->get_donor_seq_from_intron($intron))) {
+      $results{'MES-NCSS_upstream_donor_seq'} = $seq;
+      $results{'MES-NCSS_upstream_donor'} = $self->score5($seq) if $seq =~ /^[ACGT]+$/;
+    }
+
+    if (defined(my $seq = $self->get_acceptor_seq_from_intron($intron))) {
+      $results{'MES-NCSS_downstream_acceptor_seq'} = $seq;
+      $results{'MES-NCSS_downstream_acceptor'} = $self->score3($seq) if $seq =~ /^[ACGT]+$/;
+    }
+
+    # don't calculate an upstream acceptor score if the intron is the first in the transcript
+    unless ($intron_number == 1) {
+      my $upstream_intron = $introns->[$intron_idx - 1];
+
+      if (defined(my $seq = $self->get_acceptor_seq_from_intron($upstream_intron))) {
+        $results{'MES-NCSS_upstream_acceptor_seq'} = $seq;
+        $results{'MES-NCSS_upstream_acceptor'} = $self->score3($seq) if $seq =~ /^[ACGT]+$/;
+      }
+    }
+
+    # don't calculate a downstream donor score if the intron is the last in the transcript
+    unless ($intron_number == $total_introns) {
+      my $downstream_intron = $introns->[$intron_idx + 1];
+
+      if (defined(my $seq = $self->get_donor_seq_from_intron($downstream_intron))) {
+        $results{'MES-NCSS_downstream_donor_seq'} = $seq;
+        $results{'MES-NCSS_downstream_donor'} = $self->score5($seq) if $seq =~ /^[ACGT]+$/;
+      }
+    }
+  }
+
+  elsif ($tv->exon_number) {
+
+    my ($exon_numbers, $total_exons) = split(/\//, $tv->exon_number);
+    my $exon_number = (split(/-/, $exon_numbers))[0];
+
+    my $exons = $tr->get_all_Exons;
+
+    my $exon_idx = $exon_number - 1;
+    my $exon = $exons->[$exon_idx];
+
+    # don't calculate upstream scores if the exon is the first in the transcript
+    unless ($exon_number == 1) {
+      my $upstream_exon = $exons->[$exon_idx - 1];
+
+      if (defined(my $seq = $self->get_donor_seq_from_exon($upstream_exon))) {
+        $results{'MES-NCSS_upstream_donor_seq'} = $seq;
+        $results{'MES-NCSS_upstream_donor'} = $self->score5($seq) if $seq =~ /^[ACGT]+$/;
+      }
+
+      if (defined(my $seq = $self->get_acceptor_seq_from_exon($exon))) {
+        $results{'MES-NCSS_upstream_acceptor_seq'} = $seq;
+        $results{'MES-NCSS_upstream_acceptor'} = $self->score3($seq) if $seq =~ /^[ACGT]+$/;
+      }
+    }
+
+    # don't calculate downstream scores if the exon is the last exon in the transcript
+    unless ($exon_number == $total_exons) {
+      my $downstream_exon = $exons->[$exon_idx + 1];
+
+      if (defined(my $seq = $self->get_donor_seq_from_exon($exon))) {
+        $results{'MES-NCSS_downstream_donor_seq'} = $seq;
+        $results{'MES-NCSS_downstream_donor'} = $self->score5($seq) if $seq =~ /^[ACGT]+$/;
+      }
+
+      if (defined(my $seq = $self->get_acceptor_seq_from_exon($downstream_exon))) {
+        $results{'MES-NCSS_downstream_acceptor_seq'} = $seq;
+        $results{'MES-NCSS_downstream_acceptor'} = $self->score3($seq) if $seq =~ /^[ACGT]+$/;
+      }
+    }
+  }
+
+  return \%results;
+}
+
+
+## Sliding window approach methods
+##################################
+
+sub get_max_donor {
+  my ($self, $sequence) = @_;
+
+  my ($seq, $frame, $max);
+  my @kmers = @{$self->sliding_window($sequence, 9)};
+
+  for my $i (0 .. $#kmers) {
+    my $kmer = $kmers[$i];
+    my $score = $self->score5($kmer);
+    if(!$max || $score > $max) {
+      $seq = $kmer;
+      $frame = $i + 1;
+      $max = $score;
+    }
+  }
+  return [$seq, $frame, $max];
+}
+
+sub get_max_acceptor {
+  my ($self, $sequence) = @_;
+
+  my ($seq, $frame, $max);
+  my @kmers = @{$self->sliding_window($sequence, 23)};
+
+  for my $i (0 .. $#kmers) {
+    my $kmer = $kmers[$i];
+    my $score = $self->score3($kmer);
+    if(!$max || $score > $max) {
+      $seq = $kmer;
+      $frame = $i + 1;
+      $max = $score;
+    }
+  }
+  return [$seq, $frame, $max];
+}
+
+sub sliding_window {
+  my ($self, $sequence, $winsize) = @_;
+  my @seqs;
+  for (my $i = 1; $i <= length($sequence) - $winsize + 1; $i++) {
+    push @seqs, substr($sequence, $i - 1, $winsize);
+  }
+  return \@seqs;
+}
+
+
+## Nearest canonical splice site methods
+########################################
+
+sub get_donor_seq_from_exon {
+  my ($self, $exon) = @_;
+
+  my ($start, $end);
+
+  if ($exon->strand > 0) {
+    ($start, $end) = ($exon->end - 2, $exon->end + 6);
+  }
+  else {
+    ($start, $end) = ($exon->start - 6, $exon->start + 2);
+  }
+
+  my $slice = $exon->slice()->sub_Slice($start, $end, $exon->strand);
+  my $seq = $slice->seq() if defined($slice);
+
+  return $seq;
+}
+
+sub get_acceptor_seq_from_exon {
+  my ($self, $exon) = @_;
+
+  my ($start, $end);
+
+  if ($exon->strand > 0) {
+    ($start, $end) = ($exon->start - 20, $exon->start + 2);
+  }
+  else {
+    ($start, $end) = ($exon->end - 2, $exon->end + 20);
+  }
+
+  my $slice = $exon->slice()->sub_Slice($start, $end, $exon->strand);
+  my $seq = $slice->seq() if defined($slice);
+
+  return $seq;
+}
+
+sub get_donor_seq_from_intron {
+  my ($self, $intron) = @_;
+
+  my ($start, $end);
+
+  if ($intron->strand > 0) {
+    ($start, $end) = ($intron->start - 3, $intron->start + 5);
+  }
+  else {
+    ($start, $end) = ($intron->end - 5, $intron->end + 3);
+  }
+
+  my $slice = $intron->slice()->sub_Slice($start, $end, $intron->strand);
+  my $seq = $slice->seq() if defined($slice);
+
+  return $seq;
+}
+
+sub get_acceptor_seq_from_intron {
+  my ($self, $intron) = @_;
+
+  my ($start, $end);
+
+  if ($intron->strand > 0) {
+    ($start, $end) = ($intron->end - 19, $intron->end + 3);
+  }
+  else {
+    ($start, $end) = ($intron->start - 3, $intron->start + 19);
+  }
+
+  my $slice = $intron->slice()->sub_Slice($start, $end, $intron->strand);
+  my $seq = $slice->seq() if defined($slice);
+
+  return $seq;
+}
+
+
+## Common methods
+#################
+
+sub get_seqs {
+  my ($self, $tva, $start, $end) = @_;
+  my $vf = $tva->variation_feature;
+
+  my $tr_strand = $tva->transcript->strand;
+
+  my $ref_slice = $vf->{slice}->sub_Slice($start, $end, $tr_strand);
+
+  my ($ref_seq, $alt_seq);
+
+  if (defined $ref_slice) {
+
+    $ref_seq = $alt_seq = $ref_slice->seq();
+
+    my $substr_start = $tr_strand > 0 ? $vf->{start} - $start : $end - $vf->{end};
+    my $feature_seq = $tva->seq_length > 0 ? $tva->feature_seq : '';
+
+    substr($alt_seq, $substr_start, ($vf->{end} - $vf->{start}) + 1) = $feature_seq;
+  }
+
+  return [$ref_seq, $alt_seq];
+}
+
+sub score5 {
+  my $self = shift;
+  my $seq = shift;
+  my $hex = md5_hex($seq);
+
+  # check cache
+  if($self->{cache}) {
+    my ($res) = grep {$_->{hex} eq $hex} @{$self->{cache}->{score5}};
+
+    return $res->{score} if $res; 
+  }
+
+  my $a = $self->score5_scoreconsensus($seq);
+  die("ERROR: No score5_scoreconsensus\n") unless defined($a);
+
+  my $b = $self->score5_getrest($seq);
+  die("ERROR: No score5_getrest\n") unless defined($b);
+
+  my $c = $self->{'score5_seq'}->{$b};
+  die("ERROR: No score5_seq for $b\n") unless defined($c);
+
+  my $d = $self->{'score5_me2x5'}->{$c};
+  die("ERROR: No score5_me2x5 for $c\n") unless defined($d);
+
+  my $score = $self->log2($a * $d);
+
+  # cache it
+  push @{$self->{cache}->{score5}}, { hex => $hex, score => $score };
+  shift @{$self->{cache}->{score5}} while scalar @{$self->{cache}->{score5}} > $CACHE_SIZE;
+
+  return $score;
+}
+
+sub score3 {
+  my $self = shift;
+  my $seq = shift;
+  my $hex = md5_hex($seq);
+
+  # check cache
+  if($self->{cache}) {
+    my ($res) = grep {$_->{hex} eq $hex} @{$self->{cache}->{score3}};
+
+    return $res->{score} if $res; 
+  }
+
+  my $a = $self->score3_scoreconsensus($seq);
+  die("ERROR: No score3_scoreconsensus\n") unless defined($a);
+
+  my $b = $self->score3_getrest($seq);
+  die("ERROR: No score3_getrest\n") unless defined($b);
+
+  my $c = $self->score3_maxentscore($b, $self->{'score3_metables'});
+  die("ERROR: No score3_maxentscore for $b\n") unless defined($c);
+
+  my $score = $self->log2($a * $c);
+
+  # cache it
+  push @{$self->{cache}->{score3}}, { hex => $hex, score => $score };
+  shift @{$self->{cache}->{score3}} while scalar @{$self->{cache}->{score3}} > $CACHE_SIZE;
+
+  return $score;
+}
+
+
+## methods copied from score5.pl
+################################
+
+sub score5_makesequencematrix {
+  my $self = shift;
+  my $file = shift;
+  my %matrix;
+  my $n=0;
+  open(SCOREF, $file) || die "Can't open $file!\n";
+  while(<SCOREF>) { 
+    chomp;
+    $_=~ s/\s//;
+    $matrix{$_} = $n;
+    $n++;
+  }
+  close(SCOREF);
+  return \%matrix;
+}
+
+sub score5_makescorematrix {
+  my $self = shift;
+  my $file = shift;
+  my %matrix;
+  my $n=0;
+  open(SCOREF, $file) || die "Can't open $file!\n";
+  while(<SCOREF>) { 
+    chomp;
+    $_=~ s/\s//;
+    $matrix{$n} = $_;
+    $n++;
+  }
+  close(SCOREF);
+  return \%matrix;
+}
+
+sub score5_getrest {
+  my $self = shift;
+  my $seq = shift;
+  my @seqa = split(//,uc($seq));
+  return $seqa[0].$seqa[1].$seqa[2].$seqa[5].$seqa[6].$seqa[7].$seqa[8];
+}
+
+sub score5_scoreconsensus {
+  my $self = shift;
+  my $seq = shift;
+  my @seqa = split(//,uc($seq));
+  my %bgd; 
+  $bgd{'A'} = 0.27; 
+  $bgd{'C'} = 0.23; 
+  $bgd{'G'} = 0.23; 
+  $bgd{'T'} = 0.27;  
+  my %cons1;
+  $cons1{'A'} = 0.004;
+  $cons1{'C'} = 0.0032;
+  $cons1{'G'} = 0.9896;
+  $cons1{'T'} = 0.0032;
+  my %cons2;
+  $cons2{'A'} = 0.0034; 
+  $cons2{'C'} = 0.0039; 
+  $cons2{'G'} = 0.0042; 
+  $cons2{'T'} = 0.9884;
+  my $addscore = $cons1{$seqa[3]}*$cons2{$seqa[4]}/($bgd{$seqa[3]}*$bgd{$seqa[4]}); 
+  return $addscore;
+}
+
+sub log2 {
+  my ($self, $val) = @_;
+  return log($val)/log(2);
+}
+
+
+## methods copied from score3.pl
+################################
+
+sub score3_hashseq {
+  #returns hash of sequence in base 4
+  # $self->score3_hashseq('CAGAAGT') returns 4619
+  my $self = shift;
+  my $seq = shift;
+  $seq = uc($seq);
+  $seq =~ tr/ACGT/0123/;
+  my @seqa = split(//,$seq);
+  my $sum = 0;
+  my $len = length($seq);
+  my @four = (1,4,16,64,256,1024,4096,16384);
+  my $i=0;
+  while ($i<$len) {
+    $sum+= $seqa[$i] * $four[$len - $i -1] ;
+    $i++;
+  }
+  return $sum;
+}
+
+sub score3_makemaxentscores {
+  my $self = shift;
+  my $dir = $self->{'_dir'}."/splicemodels/";
+  my @list = ('me2x3acc1','me2x3acc2','me2x3acc3','me2x3acc4',
+    'me2x3acc5','me2x3acc6','me2x3acc7','me2x3acc8','me2x3acc9');
+  my @metables;
+  my $num = 0 ;
+  foreach my $file (@list) {
+    my $n = 0;
+    open (SCOREF,"<".$dir.$file) || die "Can't open $file!\n";
+    while(<SCOREF>) {
+      chomp;
+      $_=~ s/\s//;
+      $metables[$num]{$n} = $_;
+      $n++;
+    }
+    close(SCOREF);
+    #print STDERR $file."\t".$num."\t".$n."\n";
+    $num++;
+  }
+  return \@metables;
+}
+
+sub score3_maxentscore {
+  my $self = shift;
+  my $seq = shift;
+  my $table_ref = shift;
+  my @metables = @$table_ref;
+  my @sc;
+  $sc[0] = $metables[0]{$self->score3_hashseq(substr($seq,0,7))};
+  $sc[1] = $metables[1]{$self->score3_hashseq(substr($seq,7,7))};
+  $sc[2] = $metables[2]{$self->score3_hashseq(substr($seq,14,7))};
+  $sc[3] = $metables[3]{$self->score3_hashseq(substr($seq,4,7))};
+  $sc[4] = $metables[4]{$self->score3_hashseq(substr($seq,11,7))};
+  $sc[5] = $metables[5]{$self->score3_hashseq(substr($seq,4,3))};
+  $sc[6] = $metables[6]{$self->score3_hashseq(substr($seq,7,4))};
+  $sc[7] = $metables[7]{$self->score3_hashseq(substr($seq,11,3))};
+  $sc[8] = $metables[8]{$self->score3_hashseq(substr($seq,14,4))};
+  my $finalscore = $sc[0] * $sc[1] * $sc[2] * $sc[3] * $sc[4] / ($sc[5] * $sc[6] * $sc[7] * $sc[8]);
+  return $finalscore;
+}
+
+sub score3_getrest {
+  my $self = shift;
+  my $seq = shift;
+  my $seq_noconsensus = substr($seq,0,18).substr($seq,20,3);
+  return $seq_noconsensus;
+}
+
+sub score3_scoreconsensus {
+  my $self = shift;
+  my $seq = shift;
+  my @seqa = split(//,uc($seq));
+  my %bgd; 
+  $bgd{'A'} = 0.27; 
+  $bgd{'C'} = 0.23; 
+  $bgd{'G'} = 0.23; 
+  $bgd{'T'} = 0.27;  
+  my %cons1;
+  $cons1{'A'} = 0.9903;
+  $cons1{'C'} = 0.0032;
+  $cons1{'G'} = 0.0034;
+  $cons1{'T'} = 0.0030;
+  my %cons2;
+  $cons2{'A'} = 0.0027; 
+  $cons2{'C'} = 0.0037; 
+  $cons2{'G'} = 0.9905; 
+  $cons2{'T'} = 0.0030;
+  my $addscore = $cons1{$seqa[18]} * $cons2{$seqa[19]}/ ($bgd{$seqa[18]} * $bgd{$seqa[19]}); 
+  return $addscore;
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/NearestGene.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,122 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ NearestGene
+
+=head1 SYNOPSIS
+
+ mv NearestGene.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --cache --plugin NearestGene
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+ finds the nearest gene(s) to a non-genic variant. More than one gene
+ may be reported if the genes overlap the variant or if genes are
+ equidistant.
+
+ Various parameters can be altered by passing them to the plugin command:
+
+ - limit     : limit the number of genes returned (default: 1)
+ - range     : initial search range in bp (default: 1000)
+ - max_range : maximum search range in bp (default: 10000)
+
+ Parameters are passed e.g.:
+
+ --plugin NearestGene,limit=3,max_range=50000
+
+=cut
+
+package NearestGene;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+my %CONFIG = (
+  limit => 1,
+  range => 1000,
+  max_range => 10000,
+);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+  
+  my $params = $self->params;
+
+  foreach my $param(@$params) {
+    my ($key, $val) = split('=', $param);
+    die("ERROR: Failed to parse parameter $param\n") unless defined($key) && defined($val);
+    $CONFIG{$key} = $val;
+  }
+  
+  return $self;
+}
+
+sub feature_types {
+  return ['Intergenic','MotifFeature','RegulatoryFeature'];
+}
+
+sub variant_feature_types {
+  return ['BaseVariationFeature'];
+}
+
+sub get_header_info {
+  return {
+    NearestGene => "Ensembl identifier of nearest gene"
+  };
+}
+
+sub run {
+  my ($self, $vfoa) = @_;
+  
+  my $vf = $vfoa->base_variation_feature;
+  my $loc_string = sprintf("%s:%i-%i", $vf->{chr} || $vf->seq_region_name, $vf->{start}, $vf->{end});
+  
+  if(!exists($self->{_cache}) || !exists($self->{_cache}->{$loc_string})) {
+    $self->{config}->{ga} = $self->{config}->{reg}->get_adaptor($self->{config}->{species}, $self->{config}->{core_type}, 'gene');
+    $self->{ga} ||= $self->{config}->{ga};
+    die("ERROR: Could not get gene adaptor; this plugin does not work in --offline mode\n") unless $self->{ga};
+
+    my %opts = map {'-'.$_ => $CONFIG{$_}} keys %CONFIG;
+    $opts{-feature} = $vf;
+    
+    my @result = map {$_->[0]->stable_id} @{
+      $self->{ga}->fetch_all_by_outward_search(%opts)
+    };
+    
+    $self->{_cache}->{$loc_string} = scalar @result ? join(",", @result) : undef;
+  }
+  
+  return $self->{_cache}->{$loc_string} ? { NearestGene => $self->{_cache}->{$loc_string} } : {};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/NonSynonymousFilter.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,65 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ NonSynonymousFilter
+
+=head1 SYNOPSIS
+
+ mv NonSynonymousFilter.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin NonSynonymousFilter
+
+=head1 DESCRIPTION
+
+ A simple example VEP filter plugin that limits output to non-synonymous variants
+
+=cut
+
+package NonSynonymousFilter;
+
+use strict;
+use warnings;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepFilterPlugin);
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub include_line {
+    my ($self, $tva) = @_;
+
+    # just check if there are alternative amino acids in the 
+    # pep_allele_string, this means we'll catch stop gained
+    # or lost as well
+
+    if (my $pep_alleles = $tva->pep_allele_string) {
+        return $pep_alleles =~ /\//;
+    }
+
+    return 0;
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/PON_P2.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,107 @@
+=head1 NAME
+ PON_P2
+ 
+=head1 SYNOPSIS
+ mv PON_P2.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin PON_P2,/path/to/python/script/ponp2.py,hg37
+ 
+=head1 DESCRIPTION
+ This plugin for Ensembl Variant Effect Predictor (VEP) computes the predictions of PON-P2
+ for amino acid substitutions in human proteins. PON-P2 is developed and maintained by
+ Protein Structure and Bioinformatics Group at Lund University and is available at 
+ http://structure.bmc.lu.se/PON-P2/.
+ 
+ To run this plugin, you will require a python script and its dependencies (Python,
+ python suds). The python file can be downloaded from http://structure.bmc.lu.se/PON-P2/vep.html/
+ and the complete path to this file must be supplied while using this plugin.
+ 
+=head1 CONTACT
+Abhishek Niroula <[e-mail]>
+Mauno Vihinen <[e-mail]>
+
+=cut
+
+package PON_P2;
+
+
+use strict;
+use warnings;
+
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+use Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+
+sub feature_types {
+	return ['Transcript'];
+}
+
+
+sub get_header_info {
+	return {
+		PON_P2 => "PON-P2 prediction and score for amino acid substitutions"
+	};
+}
+
+
+sub new {
+	my $class = shift;
+	my $self = $class->SUPER::new(@_);
+	# get parameters
+	my $command = $self->params->[0];
+	my $Hg = $self->params->[1];
+	die 'ERROR: Path to python script not specified! Specify path to python script e.g. --plugin PON_P2,/path/to/python/client/for/ponp2.py,[hg37/hg38]\n' unless defined($command);
+	die 'ERROR: Reference genome not specified! Specify the reference genome after the path to python file e.g. --plugin PON_P2,/path/to/python/client/for/ponp2.py,[hg37/hg38]\n' unless defined($command);
+	die "ERROR: Wrong reference genome specified! It should be either 'hg37' or 'hg38'\n" unless ($Hg ~~ ["hg37","hg38"]);
+	die 'ERROR: Incorrect path to ponp2.py\n' unless -e $command;
+	$self->{command} = $command;
+	$self->{Hg} = $Hg;
+	return $self;
+}
+
+
+sub run {
+	my ($self, $tva) = @_;
+
+	# only for missense variants
+	return {} unless grep {$_->SO_term eq 'missense_variant'} @{$tva->get_all_OverlapConsequences};
+
+	## Now get the variation features
+	my $vf=$tva -> variation_feature;
+
+	## If not snp return
+	return {} unless $vf->{start} eq $vf->{end};
+
+	## get allele, reverse comp if needed
+	my $allele = $tva -> variation_feature_seq;
+	my $Variation = $tva -> hgvs_genomic;
+	my ($Chr, $Pos, $Alt) = (split /:g.|>/, $Variation)[0,1,2];
+	my $Position = substr $Pos, 0, -1;
+	my $Ref = substr $Pos, -1;
+	
+	## Check for single nucleotide substitution
+	return {} unless $Ref =~ /^[ACGT]$/;
+	return {} unless $Alt =~ /^[ACGT]$/;
+
+	my $command = $self -> {command};
+	my $Hg = $self -> {Hg};
+	my $V = $Chr."_".$Position."_".$Ref."_".$Alt;;
+
+	## Call pon-p2 python script here
+	my $ponp2Res = `python $command $V $Hg` or return {};
+	$ponp2Res =~ s/\R//g;
+
+	my ($pred, $prob) =split /\t/, $ponp2Res;
+
+	## Can PON-P2 predict?
+	return {} if $pred eq "cannot";
+
+	## Return predictions
+	return $pred && $prob ? {
+		PON_P2 => "$pred($prob)",
+	} : {};
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/Phenotypes.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,331 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ Phenotypes
+
+=head1 SYNOPSIS
+
+ mv Phenotypes.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin Phenotypes
+
+=head1 DESCRIPTION
+
+ A VEP plugin that retrieves overlapping phenotype information.
+
+ On the first run for each new version/species/assembly will
+ download a GFF-format dump to ~/.vep/Plugins/
+
+ Ensembl provides phenotype annotations mapped to a number of genomic
+ feature types, including genes, variants and QTLs.
+
+ This plugin is best used with JSON output format; the output will be
+ more verbose and include all available phenotype annotation data and
+ metadata.
+
+ For other output formats, only a concatenated list of phenotype
+ description strings is returned.
+
+ Several paramters can be set using a key=value system:
+
+ file           : provide a file path, either to create anew from the download
+                  or to point to an existing file
+
+ exclude_sources: exclude sources of phenotype information. By default
+                  HGMD and COSMIC annotations are excluded. See
+                  http://www.ensembl.org/info/genome/variation/sources_phenotype_documentation.html
+                  Separate multiple values with '&'
+
+ include_sources: force include sources, as exclude_sources
+
+ exclude_types  : exclude types of features. By default StructuralVariation
+                  and SupportingStructuralVariation annotations are excluded
+                  due to their size. Separate multiple values with '&'.
+                  Valid types: Gene, Variation, QTL, StructuralVariation,
+                  SupportingStructuralVariation, RegulatoryFeature
+
+ include_types  : force include types, as exclude_types
+
+ expand_right   : sets cache size in bp. By default annotations 100000bp (100kb)
+                  downstream of the initial lookup are cached
+
+ Example:
+
+ --plugin Phenotypes,file=${HOME}/phenotypes.gff.gz,include_types=Gene
+ 
+=cut
+
+package Phenotypes;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin);
+
+# default config
+my %DEFAULTS = (
+  exclude_sources => 'HGMD_PUBLIC&COSMIC',
+  exclude_types => 'StructuralVariation&SupportingStructuralVariation',
+  expand_right => 100000,
+);
+
+my @FIELDS = qw(seq_region_name source type start end score strand frame attributes comments);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+  
+  my $params_hash = $self->params_to_hash();
+  $DEFAULTS{$_} = $params_hash->{$_} for keys %$params_hash;
+
+  unless($DEFAULTS{file}) {
+    my $pkg = __PACKAGE__;
+    $pkg .= '.pm';
+
+    my $config = $self->{config};
+
+    my $species = $config->{species};
+    my $version = $config->{db_version} || 'Bio::EnsEMBL::Registry'->software_version;
+    my $assembly = $config->{assembly};
+
+    $DEFAULTS{file} = sprintf("%s_%s_%i_%s.bed.gz", $INC{$pkg}, $species, $version, $assembly);
+  }
+
+  $self->generate_phenotype_gff($DEFAULTS{file}) if !(-e $DEFAULTS{file}) || (-e $DEFAULTS{file}.'.lock');
+
+  $self->add_file($DEFAULTS{file});
+
+  $self->get_user_params();
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Feature','Intergenic'];
+}
+
+sub get_header_info {
+  my $self = shift;
+  return {
+    PHENOTYPES => 'Phenotypes associated with overlapping genomic features'
+  }
+}
+
+sub generate_phenotype_gff {
+  my ($self, $file) = @_;
+
+  my $config = $self->{config};
+  die("ERROR: Unable to generate GFF file in offline mode\n") if $config->{offline};
+  
+  # test bgzip
+  die "ERROR: bgzip does not seem to be in your path\n" unless `which bgzip 2>&1` =~ /bgzip$/;
+
+  unless($config->{quiet}) {
+    print STDERR "### Phenotypes plugin: Generating GFF file $file from database\n";
+    print STDERR "### Phenotypes plugin: This will take some time but it will only run once per species, assembly and release\n";
+  }
+
+  my $pfa = $self->{config}->{reg}->get_adaptor($config->{species}, 'variation', 'phenotypefeature');
+
+  print STDERR "### Phenotypes plugin: Querying database\n" unless $config->{quiet};
+
+  my $sth = $pfa->dbc->prepare(qq{
+    SELECT
+      sr.name AS seqname,
+      REPLACE(s.name, " ", "_") AS source,
+      pf.type AS feature,
+      pf.seq_region_start AS start,
+      pf.seq_region_end AS end,
+      NULL AS score,
+      IF(pf.seq_region_strand = 1, '+', '-') AS strand,
+      NULL AS frame,
+      CONCAT_WS('; ',
+        CONCAT('id=', pf.object_id),
+        CONCAT('phenotype="', REPLACE(p.description, '"', ''), '"'),
+        GROUP_CONCAT(at.code, "=", concat('"', pfa.value, '"') SEPARATOR '; ')
+      ) AS attribute
+
+      FROM
+        seq_region sr,
+        source s,
+        phenotype p,
+        phenotype_feature pf
+
+      LEFT JOIN (phenotype_feature_attrib pfa, attrib_type `at`)
+      ON (
+        pf.phenotype_feature_id = pfa.phenotype_feature_id
+        AND pfa.attrib_type_id = at.attrib_type_id
+      )
+
+      WHERE sr.seq_region_id = pf.seq_region_id
+      AND s.source_id = pf.source_id
+      AND pf.phenotype_id = p.phenotype_id
+
+      GROUP BY pf.phenotype_feature_id
+      ORDER BY pf.seq_region_id, pf.seq_region_start, pf.seq_region_end
+  }, { mysql_use_result => 1});
+
+  $sth->execute();
+
+  print STDERR "### Phenotypes plugin: Writing to file\n" unless $config->{quiet};
+
+  my $lock = "$file\.lock";
+  open LOCK, ">$lock" or die "ERROR: Unable to write to lock file $lock\n";
+  print LOCK "1\n";
+  close LOCK;
+
+  open OUT, " | bgzip -c > $file" or die "ERROR: Unable to write to file $file\n";
+
+  while(my $row = $sth->fetchrow_arrayref()) {
+    print OUT join("\t", map {defined($_) ? $_ : '.'} @$row)."\n";
+  }
+
+  close OUT;
+
+  unlink($lock);
+
+  $sth->finish();
+
+  print STDERR "### Phenotypes plugin: Indexing file with tabix\n" unless $config->{quiet};
+
+  system("tabix -p gff $file") and die("ERROR: tabix failed\n");
+
+  print STDERR "### Phenotypes plugin: All done!\n" unless $config->{quiet};
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  my $vf = $tva->variation_feature;
+  
+  # adjust coords for tabix
+  my ($s, $e) = ($vf->{start} - 1, $vf->{end});
+  
+  my $data = $self->get_data($vf->{chr}, $s, $e);
+
+  return {} unless $data && scalar @$data;
+
+  return {
+    PHENOTYPES => $self->{config}->{output_format} eq "json" ? $data : join(",", map {$_->{phenotype} =~ tr/ ;/\_\_/; $_->{phenotype}} @$data)
+  };
+}
+
+sub parse_data {
+  my ($self, $line) = @_;
+
+  my @split = split /\t/, $line;
+  
+  my $data;
+  
+  # parse split data into hash
+  for my $i(0..$#split) {
+    $data->{$FIELDS[$i]} = $split[$i];
+  }
+
+  my $inc_sources = $self->include_sources;
+  if(scalar keys %$inc_sources) {
+    return undef if $data->{source} && !$inc_sources->{$data->{source}};
+  }
+  else {
+    return undef if $data->{source} && $self->exclude_sources->{$data->{source}};
+  }
+
+  my $inc_types = $self->include_types;
+  if(scalar keys %$inc_types) {
+    return undef if $data->{type} && !$inc_types->{$data->{type}};
+  }
+  else {
+    return undef if $data->{type} && $self->exclude_types->{$data->{type}};
+  }
+
+  # parse attributes
+  if(defined($data->{attributes})) {
+    $data->{attributes} =~ s/^\s+//g;
+    
+    my %attribs;
+    
+    foreach my $pair(split /;\s*/, $data->{attributes}) {
+      my ($key, $value) = split /\=/, $pair;
+
+      next unless defined($key) and defined($value);
+      
+      # remove quote marks
+      $value =~ s/\"//g;
+
+      # avoid overwriting if an attrib key duplicates a main key
+      $key = 'attrib_'.$key if exists($data->{lc($key)});
+      
+      # lowercase key to reduce chances of mess up!
+      $data->{lc($key)} = $value;
+    }
+    
+    delete $data->{attributes};
+  }
+
+  # delete empty
+  map {delete $data->{$_}} grep {$data->{$_} eq '.' || $data->{$_} eq ''} keys %$data;
+
+  return $data;
+}
+
+sub get_start {
+  return $_[1]->{start};
+}
+
+sub get_end {
+  return $_[1]->{end};
+}
+
+sub exclude_sources {
+  return $_[0]->_generic_inc_exc('exclude_sources');
+}
+
+sub exclude_types {
+  return $_[0]->_generic_inc_exc('exclude_types');
+}
+
+sub include_sources {
+  return $_[0]->_generic_inc_exc('include_sources');
+}
+
+sub include_types {
+  return $_[0]->_generic_inc_exc('include_types');
+}
+
+sub _generic_inc_exc {
+  my ($self, $key) = @_;
+
+  if(!exists($self->{'_'.$key})) {
+    my %exc = map {$_ => 1} split('&', $DEFAULTS{$key} || '');
+    $self->{'_'.$key} = \%exc;
+  }
+
+  return $self->{'_'.$key};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/PolyPhen_SIFT.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,249 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ PolyPhen_SIFT
+
+=head1 SYNOPSIS
+
+ mv PolyPhen_SIFT.pm ~/.vep/Plugins
+ ./vep -i variations.vcf -cache --plugin PolyPhen_SIFT
+
+=head1 DESCRIPTION
+
+ A VEP plugin that retrieves PolyPhen and SIFT predictions from a
+ locally constructed sqlite database. It can be used when your main
+ source of VEP transcript annotation (e.g. a GFF file or GFF-based cache)
+ does not contain these predictions.
+
+ You must either download or create a sqlite database of the predictions.
+ You may point to the file by adding db=[file] as a parameter:
+
+ --plugin PolyPhen_SIFT,db=[file]
+
+ Human predictions (assembly-independent) are available here:
+
+ https://dl.dropboxusercontent.com/u/12936195/homo_sapiens.PolyPhen_SIFT.db
+
+ (Please note the download location of this file may change)
+
+ Place this file in $HOME/.vep to have the plugin find it automatically.
+ You may change this directory by adding dir=[dir] as a parameter:
+
+ --plugin PolyPhen_SIFT,dir=[dir]
+
+ To create the database, you must have an active database connection
+ (i.e. not using --offline) and add create_db=1 as a parameter:
+
+ --plugin PolyPhen_SIFT,create_db=1
+
+ *** NB: this will take some time!!! ***
+
+ By default the file is created as:
+
+ ${HOME}/.vep/[species].PolyPhen_SIFT.db
+ 
+=cut
+
+package PolyPhen_SIFT;
+
+use strict;
+use warnings;
+use DBI;
+use Digest::MD5 qw(md5_hex);
+use Bio::EnsEMBL::Variation::ProteinFunctionPredictionMatrix;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+
+  my $param_hash = $self->params_to_hash();
+
+  my $species = $self->config->{species} || 'homo_sapiens';
+  my $dir = $param_hash->{dir} || $self->{config}->{dir};
+  my $db = $param_hash->{db} || $dir.'/'.$species.'.PolyPhen_SIFT.db';
+
+  # create DB?
+  if($param_hash->{create_db}) {
+    die("ERROR: DB file $db already exists - remove and re-run to overwrite\n") if -e $db;
+
+    $self->{dbh} = DBI->connect("dbi:SQLite:dbname=$db","","");
+    $self->{dbh}->do("CREATE TABLE predictions(md5, analysis, matrix)");
+
+    my $sth = $self->{dbh}->prepare("INSERT INTO predictions VALUES(?, ?, ?)");
+
+    my $mysql = Bio::EnsEMBL::Registry->get_adaptor($species, 'variation', 'variation')->db->dbc->prepare(qq{
+      SELECT m.translation_md5, a.value, p.prediction_matrix
+      FROM translation_md5 m, attrib a, protein_function_predictions p
+      WHERE m.translation_md5_id = p.translation_md5_id
+      AND p.analysis_attrib_id = a.attrib_id
+    }, {mysql_use_result => 1});
+
+    my ($md5, $attrib, $matrix);
+    $mysql->execute();
+    $mysql->bind_columns(\$md5, \$attrib, \$matrix);
+    $sth->execute($md5, $attrib, $matrix) while $mysql->fetch();
+    $sth->finish();
+    $mysql->finish();
+
+    $self->{dbh}->do("CREATE INDEX md5_idx ON predictions(md5)");
+  }
+
+  die("ERROR: DB file $db not found - you need to download or create it first, see documentation in plugin file\n") unless -e $db;
+
+  $self->{initial_pid} = $$;
+  $self->{db_file} = $db;
+
+  $self->{dbh} ||= DBI->connect("dbi:SQLite:dbname=$db","","");
+  $self->{get_sth} = $self->{dbh}->prepare("SELECT md5, analysis, matrix FROM predictions WHERE md5 = ?");
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  return {
+    PolyPhen_humdiv_score => 'PolyPhen humdiv score from PolyPhen_SIFT plugin',
+    PolyPhen_humdiv_pred  => 'PolyPhen humdiv prediction from PolyPhen_SIFT plugin',
+    PolyPhen_humvar_score => 'PolyPhen humvar score from PolyPhen_SIFT plugin',
+    PolyPhen_humvar_pred  => 'PolyPhen humvar prediction from PolyPhen_SIFT plugin',
+    SIFT_score            => 'SIFT score from PolyPhen_SIFT plugin',
+    SIFT_pred             => 'SIFT prediction from PolyPhen_SIFT plugin',
+  };
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  # only for missense variants
+  return {} unless grep {$_->SO_term eq 'missense_variant'} @{$tva->get_all_OverlapConsequences};
+
+  my $tr = $tva->transcript;
+  my $tr_vep_cache = $tr->{_variation_effect_feature_cache} ||= {};
+
+  ## if predictions are not available for both tools in the cache, look in the SQLite database
+  unless(exists($tr_vep_cache->{protein_function_predictions}) &&
+     $tva->sift_prediction() && $tva->polyphen_prediction()
+   ){
+
+    # get peptide
+    unless($tr_vep_cache->{peptide}) {
+      my $translation = $tr->translate;
+      return {} unless $translation;
+      $tr_vep_cache->{peptide} = $translation->seq;
+    }
+
+    # get data, indexed on md5 of peptide sequence
+    my $md5 = md5_hex($tr_vep_cache->{peptide});
+
+    my $data = $self->fetch_from_cache($md5);
+
+    unless($data) {
+
+      # forked, reconnect to DB
+      if($$ != $self->{initial_pid}) {
+        $self->{dbh} = DBI->connect("dbi:SQLite:dbname=".$self->{db_file},"","");
+        $self->{get_sth} = $self->{dbh}->prepare("SELECT md5, analysis, matrix FROM predictions WHERE md5 = ?");
+
+        # set this so only do once per fork
+        $self->{initial_pid} = $$;
+      }
+
+      $self->{get_sth}->execute($md5);
+
+      $data = {};
+
+      while(my $arrayref = $self->{get_sth}->fetchrow_arrayref) {
+        my $analysis = $arrayref->[1];
+        my ($super_analysis, $sub_analysis) = split('_', $arrayref->[1]);
+
+        $data->{$analysis} = Bio::EnsEMBL::Variation::ProteinFunctionPredictionMatrix->new(
+          -translation_md5    => $arrayref->[0],
+          -analysis           => $super_analysis,
+          -sub_analysis       => $sub_analysis,
+          -matrix             => $arrayref->[2]
+        );
+      }
+
+      $self->add_to_cache($md5, $data);
+    }
+
+    $tr_vep_cache->{protein_function_predictions} = $data;
+  }
+
+  my $return = {};
+
+  foreach my $tool_string(qw(SIFT PolyPhen_humdiv PolyPhen_humvar)) {
+    my ($tool, $analysis) = split('_', $tool_string);
+    my $lc_tool = lc($tool);
+
+    my $pred_meth  = $lc_tool.'_prediction';
+    my $score_meth = $lc_tool.'_score';
+
+    my $pred = $tva->$pred_meth($analysis);
+
+    if($pred) {
+      $pred =~ s/\s+/\_/g;
+      $pred =~ s/\_\-\_/\_/g;
+      $return->{$tool_string.'_pred'} = $pred;
+
+      my $score = $tva->$score_meth($analysis);
+      $return->{$tool_string.'_score'} = $score if defined($score);
+    }
+  }
+
+  return $return;
+}
+
+sub fetch_from_cache {
+  my $self = shift;
+  my $md5 = shift;
+
+  my $cache = $self->{_cache} ||= [];
+
+  my ($data) = map {$_->{data}} grep {$_->{md5} eq $md5} @$cache;
+  return $data;
+}
+
+sub add_to_cache {
+  my $self = shift;
+  my $md5 = shift;
+  my $data = shift;
+
+  my $cache = $self->{_cache} ||= [];
+  push @$cache, {md5 => $md5, data => $data};
+
+  shift @$cache while scalar @$cache > 50;
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/ProteinSeqs.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,170 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ ProteinSeqs
+
+=head1 SYNOPSIS
+
+ mv ProteinSeqs.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin ProteinSeqs,reference.fa,mutated.fa
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+ prints out the reference and mutated protein sequences of any
+ proteins found with non-synonymous mutations in the input file. 
+
+ You should supply the name of file where you want to store the
+ reference protein sequences as the first argument, and a file to
+ store the mutated sequences as the second argument.
+
+ Note that, for simplicity, where stop codons are gained the plugin 
+ simply substitutes a '*' into the sequence and does not truncate the 
+ protein. Where a stop codon is lost any new amino acids encoded by the 
+ mutation are appended to the sequence, but the plugin does not attempt 
+ to translate until the next downstream stop codon. Also, the protein
+ sequence resulting from each mutation is printed separately, no attempt
+ is made to apply multiple mutations to the same protein.
+
+=cut
+
+package ProteinSeqs;
+
+use strict;
+use warnings;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub version {
+    return '2.4';
+}
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub new {
+    my $class = shift;
+
+    my $self = $class->SUPER::new(@_);
+
+    if($self->{config}->{fork}) {
+      print STDERR "WARNING: Plugin ProteinSeqs is disabling forking\n" unless $self->{config}->{quiet};
+      delete($self->{config}->{fork});
+    }
+
+    # use some default file names if none are supplied
+
+    my $ref_file = $self->params->[0] || 'reference.fa';
+    my $mut_file = $self->params->[1] || 'mutated.fa';
+
+    open $self->{ref_file}, ">$ref_file" or die "Failed to open $ref_file";
+    open $self->{mut_file}, ">$mut_file" or die "Failed to open $mut_file";
+
+    return $self;
+}
+
+sub run {
+    my ($self, $tva) = @_;
+
+    # check if we have a mutant amino acid, if not there isn't much we can do!
+
+    if (my $mut_aa = $tva->peptide) {
+        
+        # get the peptide coordinates
+
+        my $tl_start = $tva->transcript_variation->translation_start;
+        my $tl_end = $tva->transcript_variation->translation_end;
+
+        # and our reference sequence
+
+        my $ref_seq = $tva->transcript_variation->_peptide;
+
+        # splice the mutant peptide sequence into the reference sequence
+
+        my $mut_seq = $ref_seq;
+
+        substr($mut_seq, $tl_start-1, $tl_end - $tl_start + 1) = $mut_aa;
+
+        # print out our reference and mutant sequences
+
+        my $translation_id = $tva->transcript->translation->stable_id;
+        
+        # only print the reference sequence if we haven't printed it yet
+
+        $self->print_fasta($ref_seq, $translation_id, $self->{ref_file})
+            unless $self->{printed_ref}->{$translation_id}++;
+
+        # we always print the mutated sequence as each mutation may have
+        # a different consequence
+        
+        $self->print_fasta($mut_seq, $tva->hgvs_protein, $self->{mut_file});
+    }
+
+    # return an empty hashref because we don't want to add 
+    # anything to the VEP output file
+
+    return {};
+}
+
+sub print_fasta {
+    my ($self, $peptide, $id, $fh) = @_;
+
+    # break the sequence into 80 characters per line
+    
+    $peptide =~ s/(.{80})/$1\n/g;
+    
+    # get rid of any trailing newline
+    
+    chomp $peptide;
+
+    # print the sequence
+
+    print $fh ">$id\n$peptide\n";
+}
+
+sub STORABLE_freeze {
+    my ($self, $cloning) = @_;
+    return if $cloning;
+    
+    close $self->{ref_file};
+    close $self->{mut_file};
+    
+    delete $self->{ref_file};
+    delete $self->{ref_file};
+}
+
+sub STORABLE_thaw {
+    my ($self, $cloning) = @_;
+    return if $cloning;
+
+    my $ref_file = $self->params->[0] || 'reference.fa';
+    my $mut_file = $self->params->[1] || 'mutated.fa';
+
+    open $self->{ref_file}, ">>$ref_file" or die "Failed to open $ref_file";
+    open $self->{mut_file}, ">>$mut_file" or die "Failed to open $mut_file";
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/README	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,29 @@
+This repository contains several perl plugin modules for the Ensembl
+Variant Effect Predictor (VEP). Please refer to the documentation at 
+the top of each file for details of what each plugin does and how to 
+run it, though for most you will just need to put the module in your
+~/.vep/Plugins directory (or elsewhere on your $PERL5LIB) and then
+run the VEP with the argument --plugin <module name>.
+
+More documentation on VEP plugins, and on the VEP itself, can be 
+found on the Ensembl website:
+
+http://www.ensembl.org/info/docs/tools/vep/script/index.html
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+http://www.ensembl.org/info/about/code_licence.html
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/REVEL.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,125 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+
+=cut
+
+=head1 NAME
+
+ REVEL
+
+=head1 SYNOPSIS
+
+ mv REVEL.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin REVEL,/path/to/revel/data.tsv.gz
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+ adds the REVEL score for missense variants to VEP output.
+
+ Please cite the REVEL publication alongside the VEP if you use this resource:
+ https://www.ncbi.nlm.nih.gov/pubmed/27666373
+ 
+ REVEL scores can be downloaded from: https://sites.google.com/site/revelgenomics/downloads
+ and can be tabix-processed by:
+ 
+ cat revel_all_chromosomes.csv | tr "," "\t" > tabbed_revel.tsv
+ sed '1s/.*/#&/' tabbed_revel.tsv > new_tabbed_revel.tsv
+ bgzip new_tabbed_revel.tsv
+ tabix -f -s 1 -b 2 -e 2 new_tabbed_revel.tsv.gz
+
+ The tabix utility must be installed in your path to use this plugin.
+
+=cut
+package REVEL;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin);
+
+sub new {
+  my $class = shift;
+
+  my $self = $class->SUPER::new(@_);
+
+  $self->expand_left(0);
+  $self->expand_right(0);
+
+  $self->get_user_params();
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  return { REVEL => 'Rare Exome Variant Ensemble Learner '};
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  # only for missense variants
+  return {} unless grep {$_->SO_term eq 'missense_variant'} @{$tva->get_all_OverlapConsequences};
+
+  my $vf = $tva->variation_feature;
+  my $allele = $tva->variation_feature_seq;
+  my ($res) = grep {
+    $_->{alt}   eq $allele &&
+    $_->{start} eq $vf->{start} &&
+    $_->{end}   eq $vf->{end} &&
+    $_->{altaa} eq $tva->peptide
+  } @{$self->get_data($vf->{chr}, $vf->{start}, $vf->{end})};
+
+  return $res ? $res->{result} : {};
+}
+
+sub parse_data {
+  my ($self, $line) = @_;
+
+  my ($c, $s, $ref, $alt, $refaa, $altaa, $revel_value) = split /\t/, $line;
+
+  return {
+    alt => $alt,
+    start => $s,
+    end => $s,
+    altaa => $altaa,
+    result => {
+      REVEL   => $revel_value,
+    }
+  };
+}
+
+sub get_start {
+  return $_[1]->{start};
+}
+
+sub get_end {
+  return $_[1]->{end};
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/RankFilter.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,119 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ RankFilter
+
+=head1 SYNOPSIS
+
+ mv RankFilter.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin RankFilter,splice_region_variant
+
+=head1 DESCRIPTION
+
+ A VEP plugin filter that limits output of predictions to those ranked (by Ensembl)
+ to be more severe (or at least as severe) as a user specified cutoff. The user can 
+ specify either a numerical rank (lower ranks are assumed to be more severe) or an 
+ SO term to use as the (inclusive) cutoff on the VEP command line. If a term is not 
+ specified the default cutoff term used is 'splice_region_variant' (rank = 8). 
+ 
+ For reference, the table of consequence terms at:
+
+  http://www.ensembl.org/info/docs/variation/index.html#consequence_type_table
+
+ is listed in descending order of severity, so you can refer to this table
+ to pick your cutoff.
+
+=cut
+
+package RankFilter;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::Constants qw(%OVERLAP_CONSEQUENCES);
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepFilterPlugin);
+
+sub new {
+    my $class = shift;
+
+    # call the superclass constructor
+
+    my $self = $class->SUPER::new(@_);
+
+    # use splice_region_variant as our default cutoff term
+
+    my $term = $self->params->[0] || 'splice_region_variant';
+
+    my $rank;
+
+    if ($term =~ /^\d+$/) {
+        
+        # we allow the user to specify a numerical rank as 
+        # well as a term
+        
+        $rank = $term;
+    }
+    elsif (my $oc = $OVERLAP_CONSEQUENCES{$term}) {
+        
+        # otherwise we look up the rank from the provided
+        # SO consequence term
+
+        $rank = $oc->rank;
+    }
+    else {
+        die "Unable to find rank for consequence term: '$term'\n";
+    }
+
+    $self->{rank} = $rank;
+
+    return $self;
+}
+
+sub feature_types {
+    return ['Feature', 'Intergenic'];
+}
+
+sub include_line {
+    my ($self, $tva) = @_;
+
+    # check all the consequences in turn
+
+    for my $oc (@{ $tva->get_all_OverlapConsequences }) {
+        
+        # and include this line if the rank of any of the 
+        # consequences for this TVA is less than our cutoff 
+        # (lower rank is assumed to be more deleterious)
+
+        if ($oc->rank <= $self->{rank}) {
+            return 1;
+        }
+    }
+
+    return 0;
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/RefSeqHGVS.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,208 @@
+=head1 NAME
+
+ RefSeqHGVS -- provide RefSeq-based HGVS tags for VEP output
+
+=head1 SYNOPSIS
+
+ cp RefSeqHGVS.pm ~/.vep/Plugins/ (or elsewhere in PERL5LIB)
+ perl variant_effect_predictor.pl -i variations.vcf --plugin RefSeqHGVS
+
+ Output:
+ Variant lines with the following addtiional tags:
+     HGVSc-RefSeq=NM_198156.2:c.403delA;HGVSp-RefSeq=NP_937799.1:p.Arg135GlyfsX26
+
+=head1 DESCRIPTION
+
+ RefSeqHGVS is a plugin for Ensembl's Variant Effect Predictor that
+ provides variant annotatoins in HGVS format [1] using RefSeq accessions
+ (typically NM and NP).  It provides the analog to VEP's HGVSc and HGVSp
+ annotations, which use Ensembl ENST and ENSP accessions.  This module
+ relies RefSeq data in the OtherFeatures database.
+
+ Converting ENST HGVS tags to RefSeq tags is confounded subtle differences
+ between exon structures for the same CDS.  The plugin is intended to be
+ conservative by requiring exact matches of both CDS and exon structure
+ when converting variants.
+
+ [1] http://www.hgvs.org/mutnomen/
+
+=head1 BUGS AND LIMITATIONS
+
+=over
+
+=item * RefSeq transcripts limited to those in the OtherFeatures database. 
+
+Archived RefSeq transcripts are not available.
+
+=item * Discrepancies between RefSeq and GRCh37
+
+ Approximately 20% of RefSeqs differ from the GRCh37 due to substitution
+ (16.2%), insertion/deletion (3.5%), or both (1.2%) differences. [1]
+ Variants are annotated by difference with respect to the genome, not the
+ RefSeq transcript.
+
+ [1] MU2A--reconciling the genome and transcriptome to determine the
+ effects of base substitutions.
+Garla, V., Kong, Y., Szpakowski, S., & Krauthammer, M. (2011). 
+ Bioinformatics, 27(3), 416-8. doi:10.1093/bioinformatics/btq658
+ http://www.ncbi.nlm.nih.gov/pubmed/21149339
+
+=item * Conservative selection of equivalent RefSeq transcripts.
+
+Only NM transcripts which are exactly identical to the ENST transcript in
+both CDS and exon structure are used.  In the future, this might be
+relaxed to exclude only regions of mismatch.  Currently, this implies that
+HGVS tags are not constructued when the RefSeq differs from the reference
+geneome.
+
+=back
+
+=head1 CONTACT
+
+ Reece Hart <[e-mail]>
+
+=head1 LICENSE
+
+ This code and all rights to it are hereby donated to EnsEMBL project by
+ Reece Hart and Locus Development.
+
+ Copyright (c) 1999-2011 The European Bioinformatics Institute and
+ Genome Research Limited.  All rights reserved.
+
+ This software is distributed under a modified Apache license.
+ For license details, please see
+
+   http://www.ensembl.org/info/about/code_licence.html
+
+=cut
+
+
+package RefSeqHGVS;
+
+use strict;
+use warnings;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+use Data::Dumper;
+
+my %mt_cache;								# cache of ENST -> NM mappings
+
+sub version {
+  return '2.3';
+}
+
+sub new {
+  my $class = shift;
+  my $self = $class->SUPER::new(@_);
+  my $reg = 'Bio::EnsEMBL::Registry';
+
+  $self->{ofsa} = $reg->get_adaptor('Human', 'otherfeatures', 'Slice')
+	or die "Failed to create transcript adaptor in human otherfeatures database\n";
+  $self->{ofta} = $reg->get_adaptor('Human', 'otherfeatures', 'Transcript')
+	or die "Failed to create transcript adaptor in human otherfeatures database\n";
+
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub variant_feature_types {
+  return ['VariationFeature'];
+}
+
+sub get_header_info {
+  return {
+	'HGVSc-RefSeq' => "HGVSc using RefSeq transcripts accessions",
+	'HGVSp-RefSeq' => "HGVSp using RefSeq protein accessions",
+  };
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  my $t = $tva->transcript;
+  my %rv;
+
+  my $ofsa = $self->{ofsa};
+  my $ofta = $self->{ofta};
+
+  # mappabale_transcripts have identical CDS and exon structure
+  my @mappable_transcripts = $self->get_mappable_transcripts($t);
+  my @transcript_acs = map { $_->display_id() } @mappable_transcripts;
+  my @protein_acs = grep {defined $_} map { $_->translation()->display_id() } @mappable_transcripts;
+
+  # substitute accessions for those in mappable transcripts/proteins
+  my @hgvsc_rs;
+  if (defined (my $hgvsc = $tva->hgvs_coding())) {
+	@hgvsc_rs = map {__subst_hgvs_ac($hgvsc ,$_)} @transcript_acs;
+  }
+  my @hgvsp_rs;
+  if (defined (my $hgvsp = $tva->hgvs_protein())) {
+	@hgvsp_rs = map {__subst_hgvs_ac($hgvsp,$_)} @protein_acs;
+  }
+
+  $rv{'HGVSc-RefSeq'} = join(';',@hgvsc_rs) if @hgvsc_rs;
+  $rv{'HGVSp-RefSeq'} = join(';',@hgvsp_rs) if @hgvsp_rs;
+  return \%rv;
+}
+
+
+sub get_mappable_transcripts {
+  my ($self,$t) = @_;
+  my $key = $t->display_id();
+  if (not exists $mt_cache{$key}) {
+	@{$mt_cache{$key}} = $self->_get_mappable_transcripts($t);
+  }
+  return @{$mt_cache{$key}};
+}
+
+
+############################################################################
+## internal methods
+sub _get_mappable_transcripts {
+  my ($self,$t) = @_;
+  my $cds_seq = $t->translateable_seq();
+  my $exon_structure = __tx_exon_str($t);
+
+  # cds_seq is empty for pseudogenes; no mapping possible
+  return () if ($cds_seq eq '');
+
+  # get overlapping transcripts from other features
+  my @tx = @{ $self->{ofta}->fetch_all_by_Slice($t->feature_Slice()) };
+
+  # limit to NMs with standard-format
+  @tx = grep { $_->display_id() =~ m/^NM_\d+\.\d+$/ } @tx;
+
+  # limit to transcripts with same CDS
+  @tx = grep { $_->translateable_seq() eq $cds_seq } @tx;
+
+  # limit to transcripts with identical chromosomal exon structure
+  @tx = grep { __tx_exon_str($_->transform('chromosome')) eq $exon_structure } @tx;
+
+  return @tx;
+}
+
+
+############################################################################
+## function (not methods)
+
+sub __tx_exon_str {
+  my $t = shift;
+  return join(',', map {sprintf('[%s,%s]', $_->start(), $_->end())} 
+				@{ $t->get_all_translateable_Exons() } );
+}
+
+sub __subst_hgvs_ac {
+  my ($hgvs,$ac) = @_;
+  $hgvs =~ s/^[^:]+:/$ac:/;
+  return $hgvs;
+}
+
+sub __uniq {
+  return keys %{{ map {$_=>1} @_ }};
+}
+
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/SameCodon.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,117 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ SameCodon
+
+=head1 SYNOPSIS
+
+ mv SameCodon.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin SameCodon
+
+=head1 DESCRIPTION
+
+ A VEP plugin that reports existing variants that fall in the same codon.
+
+=cut
+
+package SameCodon;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub version {
+    return '3.0';
+}
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub get_header_info {
+    return {
+        SameCodon => "Existing variant IDs that fall in the same codon",
+    };
+}
+
+sub run {
+  
+    my ($self, $tva) = @_;
+
+    if ($self->config->{offline}) {
+      die "A connection to the database is required to use the plugin SameCodon\n";
+    }
+    
+    my $tv = $tva->transcript_variation;
+    my $vf = $tv->variation_feature;
+    my ($pep_start, $pep_end) = ($tv->translation_start, $tv->translation_end);
+    my ($vf_start, $vf_end) = ($vf->start, $vf->end);
+    
+    return {} unless defined($pep_start) && defined($pep_end);
+    
+    my $config = $self->{config};
+    
+    # we need to map the TV start and end coords to the genome
+    # needs to be done through the mapper in case the codon spans exons
+    my $mapper = $tv->_mapper();
+    
+    return {} unless defined($mapper);
+    
+    my @coords = $mapper->pep2genomic($pep_start, $pep_end);
+    
+    return {} unless scalar @coords;
+    return {} if grep {!$_->isa('Bio::EnsEMBL::Mapper::Coordinate')} @coords;
+    
+    my @results;
+    # we might get multiple "slices" if the codon that the variant falls in spans exons
+    foreach my $coord(@coords) {
+        
+        my ($slice_start, $slice_end) = ($coord->start, $coord->end);
+        
+        my $sub_slice = $vf->slice->sub_Slice($slice_start, $slice_end);
+        my $vf_adaptor = $vf->slice->_get_VariationFeatureAdaptor();
+        push @results,
+            map {$_->variation_name}
+            grep {
+                $_->variation_name ne $vf->variation_name &&
+                $_->seq_region_start != $vf_start &&
+                $_->seq_region_end != $vf_end &&
+                scalar $mapper->genomic2cds($_->seq_region_start, $_->seq_region_end, 1) >= 1
+            }
+            @{$vf_adaptor->fetch_all_by_Slice_SO_terms($sub_slice)};
+    }
+    
+    return {} unless scalar @results;
+    
+    return {
+        SameCodon => join ",", @results
+    }
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/SpliceRegion.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,184 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+   http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <[e-mail]>
+  
+=cut
+
+=head1 NAME
+
+ SpliceRegion
+
+=head1 SYNOPSIS
+
+ mv SpliceRegion.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin SpliceRegion
+ 
+ To only show the additional consequence extended_intronic_splice_region_variant, use: 
+ ./vep -i variations.vcf --plugin SpliceRegion,Extended
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+ provides more granular predictions of splicing effects.
+
+ Three additional terms may be added:
+
+ # splice_donor_5th_base_variant : variant falls in the 5th base after the splice donor junction (5' end of intron)
+
+             v
+ ...EEEEEIIIIIIIIII...
+
+ (E = exon, I = intron, v = variant location)
+
+ # splice_donor_region_variant : variant falls in region between 3rd and 6th base after splice junction (5' end of intron)
+
+           vv vvv
+ ...EEEEEIIIIIIIIII...
+
+ # splice_polypyrimidine_tract_variant : variant falls in polypyrimidine tract at 3' end of intron, between 17 and 3 bases from the end
+
+      vvvvvvvvvvvvvvv
+ ...IIIIIIIIIIIIIIIIIIIIEEEEE...
+
+
+=cut
+
+package SpliceRegion;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::VariationEffect qw(overlap);
+use Bio::EnsEMBL::Variation::Utils::Constants qw(%OVERLAP_CONSEQUENCES);
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+my %TERM_RANK = (
+  splice_donor_5th_base_variant => 1,
+  splice_donor_region_variant => 2,
+  splice_polypyrimidine_tract_variant => 3,
+  extended_intronic_splice_region_variant_5prime => 4,
+  extended_intronic_splice_region_variant_3prime => 5,
+);
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  return {
+    SpliceRegion => "SpliceRegion predictions",
+  };
+}
+
+sub run {
+  my ($self, $tva) = @_;
+
+  my $vf = $tva->variation_feature;
+  my ($vf_start, $vf_end) = ($vf->{start}, $vf->{end});
+
+  my $is_insertion = 0;
+  if($vf_start > $vf_end) {
+    ($vf_start, $vf_end) = ($vf_end, $vf_start);
+    $is_insertion = 1;
+  }
+
+  my $tv = $tva->transcript_variation;
+  my $tr = $tv->transcript;
+  my $vf_tr_seq = $tva->feature_seq;
+
+  # define some variables depending on transcript strand
+  my ($strand_mod, $donor_coord, $acc_coord);
+  if($tr->strand > 0) {
+    $strand_mod = 1;
+    $donor_coord = 'start';
+    $acc_coord = 'end';
+  }
+  else {
+    $strand_mod = -1;
+    $donor_coord = 'end';
+    $acc_coord = 'start';
+  }
+
+  my %results;
+
+  my @terms;
+  my $extended_flag = lc($self->params->[0] || "") eq 'extended';
+  for my $intron(@{$tv->_overlapped_introns($vf_start, $vf_end)}) {
+
+    # define terms to check for and their regions
+    @terms = (
+      {
+        term => 'splice_donor_5th_base_variant',
+        region => [$intron->{$donor_coord} + (4 * $strand_mod), $intron->{$donor_coord} + (4 * $strand_mod)]
+      },
+      {
+        term => 'splice_donor_region_variant',
+        region => [$intron->{$donor_coord} + (2 * $strand_mod), $intron->{$donor_coord} + (5 * $strand_mod)]
+      },
+      {
+        term => 'splice_polypyrimidine_tract_variant',
+        region => [$intron->{$acc_coord} + (-16 * $strand_mod), $intron->{$acc_coord} + (-2 * $strand_mod)],
+        # allele_specific_mod => {
+        #   A => '_to_purine',
+        #   G => '_to_purine',
+        # }
+      },
+    ) unless $extended_flag;
+    
+    @terms = (
+      {
+        term => 'extended_intronic_splice_region_variant_5prime',
+        region => [$intron->{$donor_coord}, $intron->{$donor_coord} + (9 * $strand_mod)]
+      },
+      {
+        term => 'extended_intronic_splice_region_variant_3prime',
+        region => [$intron->{$acc_coord} + (-9 * $strand_mod), $intron->{$acc_coord} ],
+        # allele_specific_mod => {
+        #   A => '_to_purine',
+        #   G => '_to_purine',
+        # }
+      },
+    ) if $extended_flag;
+    
+
+    foreach my $term_hash(@terms) {
+      my $pass = overlap($vf_start, $vf_end, sort {$a <=> $b} @{$term_hash->{region}});
+      if($pass) {
+        my $term = $term_hash->{term};
+        $term = 'extended_intronic_splice_region_variant' if $extended_flag;
+
+        # if(my $allele_specific_mods = $term_hash->{allele_specific_mod}) {
+        #   $term .= $allele_specific_mods->{$vf_tr_seq} || '';
+        # }
+
+        $results{$term}++;
+        last;
+      }
+    }
+  }
+
+  return {} unless %results;
+
+  return { SpliceRegion => [sort {$TERM_RANK{$a} <=> $TERM_RANK{$b}} keys %results]};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/SubsetVCF.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,226 @@
+=head1 NAME
+
+ SubsetVCF
+
+=head1 DESCRIPTION
+
+ A VEP plugin to retrieve overlapping records from a given VCF file.
+ Values for POS, ID, and ALT, are retrieved as well as values for any requested
+ INFO field. Additionally, the allele number of the matching ALT is returned.
+
+ Though similar to using '--custom', this plugin returns all ALTs for a given
+ POS, as well as all associated INFO values.
+
+ By default, only VCF records with a filter value of "PASS" are returned, 
+ however this behaviour can be changed via the 'filter' option.
+
+ Parameters:
+    name: short name added used as a prefix (required)
+    file: path to tabix-index vcf file (required)
+  filter: only consider variants marked as 'PASS', 1 or 0 (default, 1)
+  fields: info fields to be returned (default, not used)
+            '%' can delimit multiple fields
+            '*' can be used as a wildcard 
+
+ Returns:
+  <name>_POS: POS field from VCF
+  <name>_REF: REF field from VCF (minimised)
+  <name>_ALT: ALT field from VCF (minimised)
+  <name>_alt_index: Index of matching variant (zero-based)
+  <name>_<field>: List of requested info values
+
+=head1 SYNOPSIS
+
+ ./vep -i variations.vcf --plugin SubsetVCF,file=filepath.vcf.gz,name=myvfc,fields=AC*%AN*
+
+=head1 CONTACT
+	
+	Joseph A. Prinz <[e-mail]>
+
+=head1 LICENSE
+
+	Licensed under the Apache License, Version 2.0 (the "License");
+	you may not use this file except in compliance with the License.
+	You may obtain a copy of the License at
+			http://www.apache.org/licenses/LICENSE-2.0
+	Unless required by applicable law or agreed to in writing, software
+	distributed under the License is distributed on an "AS IS" BASIS,
+	WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+	See the License for the specific language governing permissions and
+	limitations under the License.
+
+=cut
+
+package SubsetVCF;
+
+use strict;
+use warnings;
+
+use Storable qw(dclone);
+use Data::Dumper;
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+use Bio::EnsEMBL::Variation::Utils::Sequence qw(get_matched_variant_alleles);
+use Bio::EnsEMBL::Variation::Utils::VEP qw(parse_line get_all_consequences);
+use Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin;
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin);
+
+sub simple_vf {
+  my ($vf, $params) = @_;
+  my @alleles = split /\//, $vf->{allele_string};
+  my $ref = shift @alleles;
+
+  my @line;
+  if (ref $vf->{_line} ne "ARRAY") {
+    @line = split /\t/, $vf->{_line};
+  } else {
+    @line = @{$vf->{_line}};
+  }
+
+  # Use a particular allele if requested
+  @alleles = ($params->{allele}) if $params->{allele};
+  
+  # Reverse comp if needed
+  if ($vf->{strand} < 0) {
+    @alleles = map { reverse_comp($_) } @alleles;
+    $ref = reverse_comp($ref);
+    $vf->{strand} = 1;
+  }
+
+  # Return values
+  my $ret = {
+      chr    => $vf->{chr},
+      pos    => $vf->{start},
+      start  => $vf->{start},
+      end    => $vf->{end},
+      strand => $vf->{strand},
+      alts   => [@alleles],
+      line   => [@line],
+      ref    => $ref};
+
+  # If filter is true, only return $ret if filter eq "PASS"
+  return $params->{filter} && $line[6] ne "PASS" ? {} : $ret;
+}
+
+sub parse_info {
+  my ($line, $valid_fields) = @_;
+  my %ret;
+  for my $dat (split /;/, $line->[7]) {
+    my ($field, $val) = split /=/, $dat;
+    if (grep { $field eq $_ } @$valid_fields) {
+      $ret{$field} = [split /,/, $val];
+    }
+  }
+  return \%ret;
+}
+
+sub new {
+  my $class = shift;
+  my $self = $class->SUPER::new(@_);
+
+  $self->expand_left(0);
+  $self->expand_right(0);
+  $self->get_user_params();
+
+  # Get params and ensure a minumum number of parameters
+  my $params = $self->params_to_hash();
+  die "ERROR: no value for 'file' specified" if !$params->{file};
+  die "ERROR: no value for 'name' specified" if !$params->{name};
+
+  # Defaults
+  $params->{filter} = 1 if !$params->{filter};
+
+  # Add file via parameter hash
+  $self->add_file($params->{file});
+  $self->{filter} = $params->{filter};
+  $self->{name} = $params->{name};
+
+  if ($params->{fields}) {
+    # Mung filter to turn AC*%AN* into AC[^,]+|AN[^,]+
+    $params->{fields} =~ s/%/|/g;
+    $params->{fields} =~ s/\*/[^,]*/g;
+
+    # Get input file headers
+    my %fields;
+    my $info_regex = "^##INFO=<ID=($params->{fields}),.*Description=\"([^\"]+).*";
+    open HEAD, "tabix -fh $params->{file} 1:1-1 2>&1 | ";
+    while(my $line = <HEAD>) {
+      next unless $line =~ $info_regex;
+      $fields{$1} = $2;
+    }
+    die "Could not find any valid info fields" if not %fields;
+    $self->{fields} = \%fields;
+    $self->{valid_fields} = [keys %fields];
+  }
+  return $self;
+}
+
+sub feature_types {
+  return ['Feature', 'Intergenic'];
+}
+
+sub get_header_info {
+  my $self = shift;
+  my %ret;
+
+  # Add fields if requested
+  if ($self->{fields}) {
+    while (my ($field, $desc) = each %{$self->{fields}}) {
+      $ret{"$self->{name}_$field"} = $desc;
+    }
+  }
+
+  $ret{"$self->{name}_ID"} = "Original ID";
+  $ret{"$self->{name}_POS"} = "Original POS";
+  $ret{"$self->{name}_REF"} = "Original refrance allele";
+  $ret{"$self->{name}_ALT"} = "Original alternatives as they appear in the VCF file";
+  $ret{"$self->{name}_alt_index"} = "Index of matching alternative (zero-based)";
+  return \%ret;
+}
+
+sub parse_data {
+  my ($self, $line) = @_;
+  my ($vf) = @{parse_line({format => 'vcf', minimal => 1}, $line)};
+  return simple_vf($vf, {filter => $self->{filter}});
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  my $vf = simple_vf($tva->variation_feature, {allele => $tva->{variation_feature_seq}});
+  
+  # Zero-indexing start for tabix and adding 1 to end for VEP indels
+  my @data = @{$self->get_data($vf->{chr}, ($vf->{start} - 1), ($vf->{end} + 1))};
+
+  my (%ret, $found_vf, @matches);
+  for my $dat (@data) {
+    next unless %$dat;
+    @matches = @{get_matched_variant_alleles($vf, $dat)};
+    if (@matches) {
+      $found_vf = dclone $dat;
+      last;
+    }
+  }
+
+  if (@matches) {
+    # Return the index of matching found alleles
+    my @found_alts = map { $_->{b_index} } @matches;
+
+    # Parse info fields if needed
+    if ($self->{fields}) {
+      my %found_fields = %{parse_info($found_vf->{line}, $self->{valid_fields})};
+      while (my ($field, $val) = each %found_fields) {
+        $ret{"$self->{name}_$field"} = [@$val];
+      }
+    }
+
+    $ret{"$self->{name}_ID"} = $found_vf->{line}->[2];
+    $ret{"$self->{name}_POS"} = $found_vf->{pos};
+    $ret{"$self->{name}_POS"} = $found_vf->{pos};
+    $ret{"$self->{name}_REF"} = $found_vf->{ref};
+    $ret{"$self->{name}_ALT"} = $found_vf->{alts};
+    $ret{"$self->{name}_alt_index"} = [@found_alts]; 
+  }
+  return \%ret;
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/TSSDistance.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,85 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ TSSDistance
+
+=head1 SYNOPSIS
+
+ mv TSSDistance.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin CCDSFilter
+
+=head1 DESCRIPTION
+
+ A VEP plugin that calculates the distance from the transcription
+ start site for upstream variants.
+
+=cut
+
+package TSSDistance;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub get_header_info {
+    return {
+        TSSDistance => "Distance from the transcription start site"
+    };
+}
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub variant_feature_types {
+    return ['BaseVariationFeature'];
+}
+
+sub run {
+    my ($self, $tva) = @_;
+
+    my $t = $tva->transcript;
+    my $vf = $tva->base_variation_feature;
+
+    my $dist;
+
+    if ($t->strand == 1) {
+        $dist = $t->start - $vf->end;
+    }
+    else {
+        $dist = $vf->start - $t->end;
+    }
+
+    if ($dist > 0) {
+        return {
+            TSSDistance => $dist,
+        }
+    }
+    else {
+        return {};
+    }
+}
+
+1;

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/Wildtype.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,72 @@
+=head1 NAME
+
+ Wildtype
+
+=head1 SYNOPSIS
+
+ mv Wildtype.pm ~/.vep/Plugins
+ perl variant_effect_predictor.pl -i variations.vcf --plugin Wildtype
+
+=head1 DESCRIPTION
+
+ This is a plugin for the Ensembl Variant Effect Predictor (VEP) that
+ provides the wildtype protein sequence of a transcript.
+
+=cut
+
+package Wildtype;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub version {
+    return '1.0';
+}
+
+sub feature_types {
+    return ['Transcript'];
+}
+
+sub get_header_info {
+    return {
+        WildtypeProtein     => "The normal, non-mutated protein sequence",
+    };
+}
+
+sub run {
+    my ($self, $tva) = @_;
+
+    my $tv = $tva->transcript_variation;
+    my $tr = $tv->transcript;
+    my $cds_seq = defined($tr->{_variation_effect_feature_cache}) ? $tr->{_variation_effect_feature_cache}->{translateable_seq} : $tr->translateable_seq;
+    my $codon_seq = Bio::Seq->new(
+        -seq      => $cds_seq,
+        -moltype  => 'dna',
+        -alphabet => 'dna'
+    );
+
+    #get codon table
+    my $codon_table;
+    if(defined($tr->{_variation_effect_feature_cache})) {
+        $codon_table = $tr->{_variation_effect_feature_cache}->{codon_table} || 1;
+    }
+    else {
+        my ($attrib) = @{$tr->slice->get_all_Attributes('codon_table')};
+        $codon_table = $attrib ? $attrib->value || 1 : 1;
+    }
+
+    # translate
+    my $new_pep = $codon_seq->translate(undef, undef, undef, $codon_table)->seq();
+    $new_pep =~ s/\*.*//;
+
+    return {
+        WildtypeProtein => $new_pep,
+    };
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/config/Condel/config/condel_SP.conf	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,11 @@
+condel.dir='path/to/config/Condel/'
+
+#------------------------------------------------------------------------------
+cutoff.HumVar.sift='0.15'
+cutoff.HumVar.polyphen='0.28'
+cutoff.HUmVar.condel='0.46'
+#------------------------------------------------------------------------------
+max.HumVar.sift='1'
+max.HumVar.polyphen='1'
+
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/config/Condel/methdist/polyphen.data	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,10000 @@
+0.000	1.000	1.000
+0.000	1.000	1.000
+0.000	1.000	1.000
+0.000	1.000	1.000
+0.000	1.000	1.000
+0.001	0.981	0.891
+0.001	0.981	0.891
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+0.028	0.661	0.218
+0.027	0.661	0.218
+0.026	0.661	0.218
+0.025	0.661	0.218
+0.024	0.661	0.218
+0.023	0.661	0.218
+0.022	0.661	0.218
+0.021	0.661	0.218
+0.020	0.661	0.218
+0.019	0.609	0.181
+0.018	0.609	0.181
+0.017	0.609	0.181
+0.016	0.609	0.181
+0.015	0.609	0.181
+0.014	0.609	0.181
+0.013	0.609	0.181
+0.012	0.609	0.181
+0.011	0.609	0.181
+0.010	0.609	0.181
+0.009	0.483	0.111
+0.008	0.483	0.111
+0.007	0.483	0.111
+0.006	0.483	0.111
+0.005	0.483	0.111
+0.004	0.483	0.111
+0.003	0.483	0.111
+0.002	0.483	0.111
+0.001	0.483	0.111
+0.000	0.483	0.111

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/config/Condel/methdist/test_condel_SP.data	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,35 @@
+ENSP00000415759_D504G	0.63	0.0020
+ENSP00000415759_G15A	0.99	0.9550
+ENSP00000415759_G8R	0	0.9880
+ENSP00000415759_G90D	0.65	0.0000
+ENSP00000415759_K343E	0.21	0.0000
+ENSP00000415759_L101P	0	0.9980
+ENSP00000415759_L499I	0.26	0.0030
+ENSP00000358424_L166V	0.01	0.7650
+ENSP00000358424_K244P	0.01	0.2660
+ENSP00000358424_G9E	0	0.9990
+ENSP00000409746_G420E	0	0.9950
+ENSP00000409746_G420R	0	0.9950
+ENSP00000409746_P418H	0	0.9990
+ENSP00000242210_Y98V	0.5	0.0030
+ENSP00000242210_G241R	0.02	0.9940
+ENSP00000242210_V142P	0.01	0.0000
+ENSP00000242210_D190S	0.14	0.0010
+ENSP00000371493_V411M	0.03	0.1790
+ENSP00000284981_E693G	0	0.8990
+ENSP00000284981_E693K	0.01	0.7970
+ENSP00000209873_H160R	0.08	0.9990
+ENSP00000209873_Q15K	0	0.0060
+ENSP00000209873_S263P	0.02	0.9770
+ENSP00000376795_L78P	0.01	1.0000
+ENSP00000376795_P252A	1	0.0340
+ENSP00000287878_H383R	0.29	0.5990
+ENSP00000287878_N488I	0.12	0.1490
+ENSP00000406366_R180L	0.72	0.0020
+ENSP00000396220_R180L	0.72	0.0020
+ENSP00000404678_R41S	0.32	0.0030
+ENSP00000403575_A260E	0.03	0.9780
+ENSP00000403575_A65G	0.04	0.0040
+ENSP00000403575_D54N	0.05	0.0050
+ENSP00000399020_M162K	0.19	0.6630
+variant1_1263085_G/A    0.13    0.1

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/dbNSFP.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,383 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ dbNSFP
+
+=head1 SYNOPSIS
+
+ mv dbNSFP.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin dbNSFP,/path/to/dbNSFP.gz,col1,col2
+
+=head1 DESCRIPTION
+
+ A VEP plugin that retrieves data for missense variants from a tabix-indexed
+ dbNSFP file.
+ 
+ Please cite the dbNSFP publication alongside the VEP if you use this resource:
+ http://www.ncbi.nlm.nih.gov/pubmed/21520341
+ 
+ You must have the Bio::DB::HTS module or the tabix utility must be installed
+ in your path to use this plugin. The dbNSFP data file can be downloaded from
+ https://sites.google.com/site/jpopgen/dbNSFP.
+
+ Release 3.5a of dbNSFP uses GRCh38/hg38 coordinates and GRCh37/hg19
+ coordinates. 
+ To use plugin with GRCh37/hg19 data:
+ > wget ftp://dbnsfp:[e-mail]/dbNSFPv3.5a.zip
+ > unzip dbNSFPv3.5a.zip
+ > head -n1 dbNSFP3.5a_variant.chr1 > h
+ > cat dbNSFP3.5a_variant.chr* | grep -v ^#chr | awk '$8 != "."' | sort -k8,8 -k9,9n - | cat h - | bgzip -c > dbNSFP_hg19.gz
+ > tabix -s 8 -b 9 -e 9 dbNSFP_hg19.gz
+
+ To use plugin with GRCh38/hg38 data:
+ > wget ftp://dbnsfp:[e-mail]/dbNSFPv3.5a.zip
+ > unzip dbNSFPv3.5a.zip
+ > head -n1 dbNSFP3.5a_variant.chr1 > h
+ > cat dbNSFP3.5a_variant.chr* | grep -v ^#chr | sort -k1,1 -k2,2n - | cat h - | bgzip -c > dbNSFP.gz
+ > tabix -s 1 -b 2 -e 2 dbNSFP.gz
+ 
+ When running the plugin you must list at least one column to retrieve from the
+ dbNSFP file, specified as parameters to the plugin e.g.
+ 
+ --plugin dbNSFP,/path/to/dbNSFP.gz,LRT_score,GERP++_RS
+
+ You may include all columns with ALL; this fetches a large amount of data per
+ variant!:
+ 
+ --plugin dbNSFP,/path/to/dbNSFP.gz,ALL
+ 
+ Tabix also allows the data file to be hosted on a remote server. This plugin is
+ fully compatible with such a setup - simply use the URL of the remote file:
+ 
+ --plugin dbNSFP,http://my.files.com/dbNSFP.gz,col1,col2
+
+ The plugin replaces occurrences of ';' with ',' and '|' with '&'. However, some
+ data field columns, e.g. Interpro_domain, use the replacement characters. We
+ added a file with replacement logic for customising the required replacement
+ of ';' and '|' in dbNSFP data columns. In addition to the default replacements
+ (; to , and | to &) users can add customised replacements. Users can either modify
+ the file dbNSFP_replacement_logic in the VEP_plugins directory or provide their own
+ file as second argument when calling the plugin:
+
+ --plugin dbNSFP,/path/to/dbNSFP.gz,/path/to/dbNSFP_replacement_logic,LRT_score,GERP++_RS
+ 
+ Note that transcript sequences referred to in dbNSFP may be out of sync with
+ those in the latest release of Ensembl; this may lead to discrepancies with
+ scores retrieved from other sources.
+
+ If the dbNSFP README file is found in the same directory as the data file,
+ column descriptions will be read from this and incorporated into the VEP output
+ file header.
+ 
+=cut
+
+package dbNSFP;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin);
+
+my %INCLUDE_SO = map {$_ => 1} qw(missense_variant stop_lost stop_gained start_lost);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+
+  $self->expand_left(0);
+  $self->expand_right(0);
+  
+  # get dbNSFP file
+  my $file = $self->params->[0];
+  $self->add_file($file);
+  
+  # get headers
+  open HEAD, "tabix -fh $file 1:1-1 2>&1 | ";
+  while(<HEAD>) {
+    next unless /^\#/;
+    chomp;
+    $self->{headers} = [split];
+  }
+  close HEAD;
+  
+  die "ERROR: Could not read headers from $file\n" unless defined($self->{headers}) && scalar @{$self->{headers}};
+  
+  # check alt and Ensembl_transcriptid headers
+  foreach my $h(qw(alt Ensembl_transcriptid)) {
+    die "ERROR: Could not find required column $h in $file\n" unless grep {$_ eq $h} @{$self->{headers}};
+  }
+
+  my $i = 1; 
+  # check if 2nd argument is a file that specifies replacement logic
+  # read replacement logic 
+  my $replacement_file = $self->params->[$i];
+  if (defined $replacement_file && -e $replacement_file) {
+    $self->add_replacement_logic($replacement_file);  
+    $i++;
+  } else {
+    $self->add_replacement_logic();  
+  } 
+ 
+  # get required columns
+  while(defined($self->params->[$i])) {
+    my $col = $self->params->[$i];
+    if($col eq 'ALL') {
+      $self->{cols} = {map {$_ => 1} @{$self->{headers}}};
+      last;
+    }
+    die "ERROR: Column $col not found in header for file $file. Available columns are:\n".join(",", @{$self->{headers}})."\n" unless grep {$_ eq $col} @{$self->{headers}};
+    
+    $self->{cols}->{$self->params->[$i]} = 1;
+    $i++;
+  }
+  
+  die "ERROR: No columns selected to fetch. Available columns are:\n".join(",", @{$self->{headers}})."\n" unless defined($self->{cols}) && scalar keys %{$self->{cols}};
+  
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  my $self = shift;
+
+  if(!exists($self->{_header_info})) {
+
+    # look for readme
+    my $file_dir = $self->files->[0];
+
+    my %rm_descs;
+
+    # won't work for remote
+    if($file_dir !~ /tp\:\/\//) {
+
+      # get just dir
+      $file_dir =~ s/\/[^\/]+$/\//;
+
+      if(opendir DIR, $file_dir) {
+        my ($readme_file) = grep {/dbnsfp.*readme\.txt/i} readdir DIR;
+        closedir DIR;
+
+        if(open RM, $file_dir.$readme_file) {
+          my ($col, $reading);
+
+          # parse dbNSFP readme
+          # relevant lines look like:
+          #
+          # 1   column1_name: description blah blah
+          #     blah blah blah
+          # 2   column2_name: description blah blah
+          #     blah blah blah
+
+          while(<RM>) {
+            chomp;
+            s/\r$//g;
+
+            if(/^\d+\s/) {
+              $reading = 1;
+
+              m/^\d+\s+(.+?)\:\s+(.+)/;
+              $col = $1;
+
+              $rm_descs{$col} = '(from dbNSFP) '.$2 if $col && $2;
+            }
+            elsif($reading && /\w/) {
+              s/^\s+//;
+              $rm_descs{$col} .= ' '.$_;
+            }
+            else {
+              $reading = 0;
+            }
+          }
+
+          close RM;
+
+          # remove multiple spaces
+          $rm_descs{$_} =~ s/\s+/ /g for keys %rm_descs;
+        }
+      }
+    }
+
+    $self->{_header_info} = {map {$_ => $rm_descs{$_} || ($_.' from dbNSFP file')} keys %{$self->{cols}}};
+  }
+  
+  return $self->{_header_info};
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  # only for missense variants
+  return {} unless grep {$INCLUDE_SO{$_->SO_term}} @{$tva->get_all_OverlapConsequences};
+  
+  my $vf = $tva->variation_feature;
+  
+  return {} unless $vf->{start} eq $vf->{end};
+  
+  # get allele, reverse comp if needed
+  my $allele = $tva->variation_feature_seq;
+  reverse_comp(\$allele) if $vf->{strand} < 0;
+  
+  return {} unless $allele =~ /^[ACGT]$/;
+  
+  # get transcript stable ID
+  my $tr_id = $tva->transcript->stable_id;
+
+  my $data;
+  my $pos;
+
+  my $assembly = $self->{config}->{assembly};
+  my $chr = ($vf->{chr} =~ /MT/i) ? 'M' : $vf->{chr};
+  foreach my $tmp_data(@{$self->get_data($chr, $vf->{start} - 1, $vf->{end})}) {
+    # compare allele and transcript
+    if ($assembly eq 'GRCh37') {
+      if (exists $tmp_data->{'pos(1-coor)'}) {
+        # for dbNSFP version 2.9.1
+        $pos = $tmp_data->{'pos(1-coor)'}
+      } elsif (exists $tmp_data->{'hg19_pos(1-based)'}) {
+        # for dbNSFP version 3.5c indexed for hg19/(=GRCh37)
+        $pos =  $tmp_data->{'hg19_pos(1-based)'}
+      } else {
+        die "dbNSFP file does not contain required columns (pos(1-coor) for version 2.9.1 or hg19_pos(1-based) for version 3.5c) to use with GRCh37";
+      }
+    } else {
+      if (exists $tmp_data->{'pos(1-based)'}) {
+        $pos = $tmp_data->{'pos(1-based)'}
+      } else {
+        die "dbNSFP file does not contain required column pos(1-based) to use with GRCh38";
+      }
+    }
+
+    next unless
+      $pos == $vf->{start} &&
+      defined($tmp_data->{alt}) &&
+      $tmp_data->{alt} eq $allele;
+    
+    # make a clean copy as we're going to edit it
+    %$data = %$tmp_data;
+
+    # convert data with multiple transcript values
+    # if($data->{Ensembl_transcriptid} =~ m/\;/) {
+
+    #   # find the "index" of this transcript
+    #   my @tr_ids = split(';', $data->{Ensembl_transcriptid});
+    #   my $tr_index;
+
+    #   for my $i(0..$#tr_ids) {
+    #     $tr_index = $i;
+    #     last if $tr_ids[$tr_index] =~ /^$tr_id(\.\d+)?$/;
+    #   }
+
+    #   next unless defined($tr_index);
+
+    #   # now alter other fields
+    #   foreach my $key(keys %$data) {
+    #     if($data->{$key} =~ m/\;/) {
+    #       my @split = split(';', $data->{$key});
+    #       die("ERROR: Transcript index out of range") if $tr_index > $#split;
+    #       $data->{$key} = $split[$tr_index];
+    #     } 
+    #   }
+    # }
+    last;
+  }
+  
+  return {} unless scalar keys %$data;
+  
+  # get required data
+  my @from = @{$self->{replacement}->{default}->{from}};
+  my @to = @{$self->{replacement}->{default}->{to}};
+
+  my %return;
+  foreach my $colname (keys %$data) {
+    next if(!defined($self->{cols}->{$colname}));
+    next if($data->{$colname} eq '.');
+
+    my @from = @{$self->{replacement}->{default}->{from}};
+    my @to   = @{$self->{replacement}->{default}->{to}};
+    @from    = @{$self->{replacement}->{$colname}->{from}} if (defined $self->{replacement}->{$colname});
+    @to      = @{$self->{replacement}->{$colname}->{to}} if (defined $self->{replacement}->{$colname});
+    for my $i (0 .. $#from) {
+      $data->{$colname} =~ s/\Q$from[$i]\E/$to[$i]/g;
+    }
+    $return{$colname} = $data->{$colname};
+  }
+  
+  return \%return;
+}
+
+sub parse_data {
+  my ($self, $line) = @_;
+
+  $line =~ s/\r$//g;
+
+  my @split = split /\t/, $line;
+  
+  # parse data into hash of col names and values
+  my %data = map {$self->{headers}->[$_] => $split[$_]} (0..(scalar @{$self->{headers}} - 1));
+
+  return \%data;
+}
+
+sub get_start {  
+  return $_[1]->{'pos(1-based)'};
+}
+
+sub get_end {
+  return $_[1]->{'pos(1-based)'};
+}
+
+sub add_replacement_logic {
+  my $self = shift;
+  my $file = shift;
+  $file ||= 'dbNSFP_replacement_logic';
+  if (! -e $file) {
+    $self->{replacement}->{default}->{from} = [';', '|'];
+    $self->{replacement}->{default}->{to} = [',', '&'];
+  } else {
+    open FILE, $file;
+    while(<FILE>) {
+      chomp;
+      next if /^colname/;
+      my ($colname, $from, $to) = split/\s+/;
+      die ("ERROR: 3 values separated by whitespace are required: colname from to.") if(!($colname && $from && $to));
+      push @{$self->{replacement}->{$colname}->{from}}, $from;
+      push @{$self->{replacement}->{$colname}->{to}}, $to;
+    }
+    close FILE;
+    die("ERROR: No default replacement logic has been specified.\n") if (!defined $self->{replacement}->{default});
+  }
+}
+
+1;
+
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/dbNSFP_replacement_logic	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,5 @@
+colname from to
+default ; ,
+default | &
+Interpro_domain ; ?
+Interpro_domain | +

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/dbscSNV.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,234 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ dbscSNV
+
+=head1 SYNOPSIS
+
+  mv dbscSNV.pm ~/.vep/Plugins
+  ./vep -i variations.vcf --plugin dbscSNV,/path/to/dbscSNV1.1_GRCh38.txt.gz
+
+=head1 DESCRIPTION
+
+  A VEP plugin that retrieves data for splicing variants from a tabix-indexed
+  dbscSNV file.
+
+  Please cite the dbscSNV publication alongside the VEP if you use this resource:
+  http://nar.oxfordjournals.org/content/42/22/13534
+
+  The Bio::DB::HTS perl library or tabix utility must be installed in your path
+  to use this plugin. The dbscSNV data file can be downloaded from
+  https://sites.google.com/site/jpopgen/dbNSFP.
+
+  The file must be processed and indexed by tabix before use by this plugin.
+  dbscSNV1.1 has coordinates for both GRCh38 and GRCh37; the file must be
+  processed differently according to the assembly you use.
+
+  > wget ftp://dbnsfp:[e-mail]/dbscSNV1.1.zip
+  > unzip dbscSNV1.1.zip
+  > head -n1 dbscSNV1.1.chr1 > h
+
+  # GRCh38
+  > cat dbscSNV1.1.chr* | grep -v ^chr | sort -k5,5 -k6,6n | cat h - | bgzip -c > dbscSNV1.1_GRCh38.txt.gz
+  > tabix -s 5 -b 6 -e 6 -c c dbscSNV1.1_GRCh38.txt.gz
+
+  # GRCh37
+  > cat dbscSNV1.1.chr* | grep -v ^chr | cat h - | bgzip -c > dbscSNV1.1_GRCh37.txt.gz
+  > tabix -s 1 -b 2 -e 2 -c c dbscSNV1.1_GRCh37.txt.gz
+
+  Note that in the last command we tell tabix that the header line starts with "c";
+  this may change to the default of "#" in future versions of dbscSNV.
+
+  Tabix also allows the data file to be hosted on a remote server. This plugin is
+  fully compatible with such a setup - simply use the URL of the remote file:
+
+  --plugin dbscSNV,http://my.files.com/dbscSNV.txt.gz
+
+  Note that transcript sequences referred to in dbscSNV may be out of sync with
+  those in the latest release of Ensembl; this may lead to discrepancies with
+  scores retrieved from other sources.
+ 
+=cut
+
+package dbscSNV;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin);
+
+sub new {
+  my $class = shift;
+  
+  my $self = $class->SUPER::new(@_);
+
+  $self->expand_left(0);
+  $self->expand_right(0);
+  
+  # get dbNSFP file
+  my $file = $self->params->[0];
+  $self->add_file($file);
+
+  if(my $assembly = $self->params->[1]) {
+    $self->{_param_assembly} = $assembly;
+  }
+  
+  # get headers
+  open HEAD, "tabix -fh $file 1:1-1 2>&1 | ";
+  while(<HEAD>) {
+    chomp;
+    $self->{headers} = [split];
+  }
+  close HEAD;
+
+  # check alt and Ensembl_transcriptid headers
+  foreach my $h(qw(alt Ensembl_gene)) {
+    die "ERROR: Could not find required column $h in $file\n" unless grep {$_ eq $h} @{$self->{headers}};
+  }
+
+  # check we have hg38_pos col, only present in dbscSNV >= 1.1
+  if($self->pos_column eq 'hg38_pos') {
+    die("ERROR: Could not find hg38_pos column in $file\n") unless grep {$_ eq 'hg38_pos'} @{$self->{headers}};
+  }
+  
+  $self->{cols} = {
+    'ada_score' => 1,
+    'rf_score'  => 1
+  };
+  
+  return $self;
+}
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub variation_feature_types {
+  return ['VariationFeature'];
+}
+
+sub get_header_info {
+  return {
+    ada_score => 'dbscSNV ADA score',
+    rf_score  => 'dbscSNV RF score'
+  }
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  my $vf = $tva->variation_feature;
+  
+  return {} unless $vf->{start} eq $vf->{end};
+  # return {} unless grep {$_->SO_term =~ /splic/} @{$tva->get_all_OverlapConsequences};
+  
+  # get allele, reverse comp if needed
+  my $allele = $tva->variation_feature_seq;
+  reverse_comp(\$allele) if $vf->{strand} < 0;
+  
+  return {} unless $allele =~ /^[ACGT]$/;
+  
+  # get gene stable ID
+  my $g_id = $tva->transcript->{_gene_stable_id} || $tva->transcript->gene->stable_id;
+  
+  my $data;
+  my $pos_column = $self->pos_column;
+  
+  foreach my $tmp_data(@{$self->get_data($vf->{chr}, $vf->{start} - 1, $vf->{end})}) {
+    # compare allele and transcript
+    next unless
+      $tmp_data->{$pos_column} == $vf->{start} &&
+      defined($tmp_data->{alt}) &&
+      $tmp_data->{alt} eq $allele; # &&
+      # defined($tmp_data->{Ensembl_gene}) &&
+      # $tmp_data->{Ensembl_gene} =~ /$g_id($|;)/;
+    
+    $data = $tmp_data;
+    last;
+  }
+  
+  return {} unless scalar keys %$data;
+  
+  # get required data
+  my %return =
+    map {$_ => $data->{$_}}
+    grep {$data->{$_} ne '.'}              # ignore missing data
+    grep {defined($self->{cols}->{$_})}  # only include selected cols
+    keys %$data;
+  
+  return \%return;
+}
+
+sub parse_data {
+  my ($self, $line) = @_;
+
+  $line =~ s/\r$//g;
+
+  my @split = split /\t/, $line;
+  
+  # parse data into hash of col names and values
+  my %data = map {$self->{headers}->[$_] => $split[$_]} (0..(scalar @{$self->{headers}} - 1));
+
+  return \%data;
+}
+
+sub get_start {  
+  return $_[1]->{$_[0]->pos_column};
+}
+
+sub get_end {
+  return $_[1]->{$_[0]->pos_column};
+}
+
+sub pos_column {
+  my $self = shift;
+
+  # work out which column to use
+  unless(exists($self->{pos_column})) {  
+    if(my $assembly = $self->{_param_assembly} || $self->{config}->{assembly}) {
+      if($assembly eq 'GRCh37') {
+        $self->{pos_column} = 'pos';
+      }
+      elsif($assembly eq 'GRCh38') {
+        $self->{pos_column} = 'hg38_pos';
+      }
+      else {
+        die("ERROR: Assembly \"$assembly\" is not compatible with this plugin\n");
+      }
+    }
+    else {
+      die("ERROR: Could not establish which position column to use based on assembly; try setting assembly manually with --assembly\n");
+    }
+  }
+
+  return $self->{pos_column};
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/miRNA.pm	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,119 @@
+=head1 LICENSE
+
+Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
+Copyright [2016-2018] EMBL-European Bioinformatics Institute
+
+Licensed under the Apache License, Version 2.0 (the "License");
+you may not use this file except in compliance with the License.
+You may obtain a copy of the License at
+
+     http://www.apache.org/licenses/LICENSE-2.0
+
+Unless required by applicable law or agreed to in writing, software
+distributed under the License is distributed on an "AS IS" BASIS,
+WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
+See the License for the specific language governing permissions and
+limitations under the License.
+
+=head1 CONTACT
+
+ Ensembl <http://www.ensembl.org/info/about/contact/index.html>
+    
+=cut
+
+=head1 NAME
+
+ miRNA
+
+=head1 SYNOPSIS
+
+ mv miRNA.pm ~/.vep/Plugins
+ ./vep -i variations.vcf --plugin miRNA
+
+=head1 DESCRIPTION
+
+ A VEP plugin that determines where in the secondary structure of a miRNA a
+ variant falls.
+ 
+=cut
+
+package miRNA;
+
+use strict;
+use warnings;
+
+use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
+
+use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
+
+sub feature_types {
+  return ['Transcript'];
+}
+
+sub get_header_info {
+  my $self = shift;
+  return {
+    miRNA => 'SO term for miRNA component containing the variant'
+  }
+}
+
+sub run {
+  my ($self, $tva) = @_;
+  
+  my $tv = $tva->transcript_variation;
+  my $tr = $tva->transcript;
+  
+  # obviously this only works for *RNA transcripts
+  return {} unless $tr->biotype =~ /RNA/;
+  
+  # and it only works if the TV falls in the cDNA
+  return {} unless $tv->cdna_start && $tv->cdna_end;
+  
+  # get attribute if already cached
+  my ($attrib) = @{$tr->get_all_Attributes('ncRNA')};
+  
+  # bit of a cheat to get attrib if ncRNA attribute hasn't been cached
+  if(!$attrib && defined($self->{config}->{ta})) {
+    delete $tr->{attributes};
+    $tr->{adaptor} = $self->{config}->{ta};
+    ($attrib) = @{$tr->get_all_Attributes('ncRNA')};
+  }
+  
+  return {} unless $attrib;
+  
+  # split out string to get coords and structure string
+  my ($start, $end, $struct) = split /\s+|\:/, $attrib->value;
+  return {} unless $struct && $struct =~ /[\(\.\)]+/;
+  
+  # variant not in given structure?
+  return { miRNA => 'None' } unless $tv->cdna_start <= $end && $tv->cdna_end >= $start;
+  
+  # parse out structure
+  my @struct;
+  while($struct =~ m/([\.\(\)])([0-9]+)?/g) {
+    my $num = $2 || 1;
+    push @struct, $1 for(1..$num);
+  }
+  
+  # get struct element types overlapped by variant
+  my %chars;
+  for my $pos($tv->cdna_start..$tv->cdna_end) {
+    $pos -= $start;
+    next if $pos < 0 or $pos > scalar @struct;
+    $chars{$struct[$pos]} = 1;
+  }
+  
+  # map element types to SO terms
+  my %map = (
+    '(' => 'miRNA_stem',
+    ')' => 'miRNA_stem',
+    '.' => 'miRNA_loop'
+  );
+  
+  return {
+    miRNA => join(",", sort map {$map{$_}} keys %chars)
+  };
+}
+
+1;
+

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/plugin_config.txt	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,898 @@
+my $VEP_PLUGIN_CONFIG = {
+  "plugins" => [
+
+    ## PATHOGENICITY PREDICTIONS
+    ############################
+
+    # dbNSFP
+    # https://github.com/ensembl-variation/VEP_plugins/blob/master/dbNSFP.pm
+    # Requires tabix-indexed data file as first param
+    # Field names are listed below and rendered as a multi-selectable autocomplete text field
+    # Human, GRCh38 only (3.x), for GRCh37 use 2.9.x
+    {
+      "key" => "dbNSFP",
+      "label" => "dbNSFP",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "helptip" => "dbNSFP provides pathogenicity predictions for missense variants from various algorithms",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/dbNSFP.pm",
+      "requires_data" => 1,
+      "requires_install" => 1,
+      "params"  => [
+        #"/path/to/dbNSFP3.5a.txt.gz",
+        "@*"
+      ],
+      "species" => [
+        "homo_sapiens"
+      ],
+      "form" => [
+        {
+          "name" => "dbNSFP_fields",
+          "label" => "Fields to include",
+          "helptip" => "Fields to fetch from dbNSFP; hold down the Ctrl (Windows) / Command (Mac) button to select multiple options",
+          "value" => "",
+          'type' => 'dropdown',
+          'multiple' => 1,
+          'style' => 'height:150px',
+          'required' => 1,
+          'notes' => 'Field descriptions in <a rel="external" href="https://drive.google.com/file/d/0B60wROKy6OqcNGJ2STJlMTJONk0/view">dbNSFP README</a>',
+          # "class" => "jquery-multiselect",
+          "values" => [
+            # "chr",
+            # "pos(1-based)",
+            # "ref",
+            # "alt",
+            # "aaref",
+            # "aaalt",
+            # "rs_dbSNP150",
+            # "hg19_chr",
+            # "hg19_pos(1-based)",
+            # "hg18_chr",
+            # "hg18_pos(1-based)",
+            # "genename",
+            # "cds_strand",
+            # "refcodon",
+            # "codonpos",
+            "codon_degeneracy",
+            "Ancestral_allele",
+            "AltaiNeandertal",
+            "Denisova",
+            # "Ensembl_geneid",
+            # "Ensembl_transcriptid",
+            # "Ensembl_proteinid",
+            # "aapos",
+            # "SIFT_score",
+            # "SIFT_converted_rankscore",
+            # "SIFT_pred",
+            # "Uniprot_acc_Polyphen2",
+            # "Uniprot_id_Polyphen2",
+            # "Uniprot_aapos_Polyphen2",
+            # "Polyphen2_HDIV_score",
+            # "Polyphen2_HDIV_rankscore",
+            # "Polyphen2_HDIV_pred",
+            # "Polyphen2_HVAR_score",
+            # "Polyphen2_HVAR_rankscore",
+            # "Polyphen2_HVAR_pred",
+            "LRT_score",
+            "LRT_converted_rankscore",
+            "LRT_pred",
+            "LRT_Omega",
+            "MutationTaster_score",
+            "MutationTaster_converted_rankscore",
+            "MutationTaster_pred",
+            "MutationTaster_model",
+            "MutationTaster_AAE",
+            "MutationAssessor_UniprotID",
+            "MutationAssessor_variant",
+            "MutationAssessor_score",
+            "MutationAssessor_score_rankscore",
+            "MutationAssessor_pred",
+            "FATHMM_score",
+            "FATHMM_converted_rankscore",
+            "FATHMM_pred",
+            "PROVEAN_score",
+            "PROVEAN_converted_rankscore",
+            "PROVEAN_pred",
+            "Transcript_id_VEST3",
+            "Transcript_var_VEST3",
+            "VEST3_score",
+            "VEST3_rankscore",
+            "MetaSVM_score",
+            "MetaSVM_rankscore",
+            "MetaSVM_pred",
+            "MetaLR_score",
+            "MetaLR_rankscore",
+            "MetaLR_pred",
+            "Reliability_index",
+            "M-CAP_score",
+            "M-CAP_rankscore",
+            "M-CAP_pred",
+            "REVEL_score",
+            "REVEL_rankscore",
+            "MutPred_score",
+            "MutPred_rankscore",
+            "MutPred_protID",
+            "MutPred_AAchange",
+            "MutPred_Top5features",
+            "CADD_raw",
+            "CADD_raw_rankscore",
+            "CADD_phred",
+            "DANN_score",
+            "DANN_rankscore",
+            "fathmm-MKL_coding_score",
+            "fathmm-MKL_coding_rankscore",
+            "fathmm-MKL_coding_pred",
+            "fathmm-MKL_coding_group",
+            "Eigen_coding_or_noncoding",
+            "Eigen-raw",
+            "Eigen-phred",
+            "Eigen-PC-raw",
+            "Eigen-PC-phred",
+            "Eigen-PC-raw_rankscore",
+            "GenoCanyon_score",
+            "GenoCanyon_score_rankscore",
+            "integrated_fitCons_score",
+            "integrated_fitCons_score_rankscore",
+            "integrated_confidence_value",
+            "GM12878_fitCons_score",
+            "GM12878_fitCons_score_rankscore",
+            "GM12878_confidence_value",
+            "H1-hESC_fitCons_score",
+            "H1-hESC_fitCons_score_rankscore",
+            "H1-hESC_confidence_value",
+            "HUVEC_fitCons_score",
+            "HUVEC_fitCons_score_rankscore",
+            "HUVEC_confidence_value",
+            "GERP++_NR",
+            "GERP++_RS",
+            "GERP++_RS_rankscore",
+            "phyloP100way_vertebrate",
+            "phyloP100way_vertebrate_rankscore",
+            "phyloP20way_mammalian",
+            "phyloP20way_mammalian_rankscore",
+            "phastCons100way_vertebrate",
+            "phastCons100way_vertebrate_rankscore",
+            "phastCons20way_mammalian",
+            "phastCons20way_mammalian_rankscore",
+            "SiPhy_29way_pi",
+            "SiPhy_29way_logOdds",
+            "SiPhy_29way_logOdds_rankscore",
+            "1000Gp3_AC",
+            "1000Gp3_AF",
+            "1000Gp3_AFR_AC",
+            "1000Gp3_AFR_AF",
+            "1000Gp3_EUR_AC",
+            "1000Gp3_EUR_AF",
+            "1000Gp3_AMR_AC",
+            "1000Gp3_AMR_AF",
+            "1000Gp3_EAS_AC",
+            "1000Gp3_EAS_AF",
+            "1000Gp3_SAS_AC",
+            "1000Gp3_SAS_AF",
+            "TWINSUK_AC",
+            "TWINSUK_AF",
+            "ALSPAC_AC",
+            "ALSPAC_AF",
+            "ESP6500_AA_AC",
+            "ESP6500_AA_AF",
+            "ESP6500_EA_AC",
+            "ESP6500_EA_AF",
+            "ExAC_AC",
+            "ExAC_AF",
+            "ExAC_Adj_AC",
+            "ExAC_Adj_AF",
+            "ExAC_AFR_AC",
+            "ExAC_AFR_AF",
+            "ExAC_AMR_AC",
+            "ExAC_AMR_AF",
+            "ExAC_EAS_AC",
+            "ExAC_EAS_AF",
+            "ExAC_FIN_AC",
+            "ExAC_FIN_AF",
+            "ExAC_NFE_AC",
+            "ExAC_NFE_AF",
+            "ExAC_SAS_AC",
+            "ExAC_SAS_AF",
+            "ExAC_nonTCGA_AC",
+            "ExAC_nonTCGA_AF",
+            "ExAC_nonTCGA_Adj_AC",
+            "ExAC_nonTCGA_Adj_AF",
+            "ExAC_nonTCGA_AFR_AC",
+            "ExAC_nonTCGA_AFR_AF",
+            "ExAC_nonTCGA_AMR_AC",
+            "ExAC_nonTCGA_AMR_AF",
+            "ExAC_nonTCGA_EAS_AC",
+            "ExAC_nonTCGA_EAS_AF",
+            "ExAC_nonTCGA_FIN_AC",
+            "ExAC_nonTCGA_FIN_AF",
+            "ExAC_nonTCGA_NFE_AC",
+            "ExAC_nonTCGA_NFE_AF",
+            "ExAC_nonTCGA_SAS_AC",
+            "ExAC_nonTCGA_SAS_AF",
+            "ExAC_nonpsych_AC",
+            "ExAC_nonpsych_AF",
+            "ExAC_nonpsych_Adj_AC",
+            "ExAC_nonpsych_Adj_AF",
+            "ExAC_nonpsych_AFR_AC",
+            "ExAC_nonpsych_AFR_AF",
+            "ExAC_nonpsych_AMR_AC",
+            "ExAC_nonpsych_AMR_AF",
+            "ExAC_nonpsych_EAS_AC",
+            "ExAC_nonpsych_EAS_AF",
+            "ExAC_nonpsych_FIN_AC",
+            "ExAC_nonpsych_FIN_AF",
+            "ExAC_nonpsych_NFE_AC",
+            "ExAC_nonpsych_NFE_AF",
+            "ExAC_nonpsych_SAS_AC",
+            "ExAC_nonpsych_SAS_AF",
+            "gnomAD_exomes_AC",
+            "gnomAD_exomes_AN",
+            "gnomAD_exomes_AF",
+            "gnomAD_exomes_AFR_AC",
+            "gnomAD_exomes_AFR_AN",
+            "gnomAD_exomes_AFR_AF",
+            "gnomAD_exomes_AMR_AC",
+            "gnomAD_exomes_AMR_AN",
+            "gnomAD_exomes_AMR_AF",
+            "gnomAD_exomes_ASJ_AC",
+            "gnomAD_exomes_ASJ_AN",
+            "gnomAD_exomes_ASJ_AF",
+            "gnomAD_exomes_EAS_AC",
+            "gnomAD_exomes_EAS_AN",
+            "gnomAD_exomes_EAS_AF",
+            "gnomAD_exomes_FIN_AC",
+            "gnomAD_exomes_FIN_AN",
+            "gnomAD_exomes_FIN_AF",
+            "gnomAD_exomes_NFE_AC",
+            "gnomAD_exomes_NFE_AN",
+            "gnomAD_exomes_NFE_AF",
+            "gnomAD_exomes_SAS_AC",
+            "gnomAD_exomes_SAS_AN",
+            "gnomAD_exomes_SAS_AF",
+            "gnomAD_exomes_OTH_AC",
+            "gnomAD_exomes_OTH_AN",
+            "gnomAD_exomes_OTH_AF",
+            "gnomAD_genomes_AC",
+            "gnomAD_genomes_AN",
+            "gnomAD_genomes_AF",
+            "gnomAD_genomes_AFR_AC",
+            "gnomAD_genomes_AFR_AN",
+            "gnomAD_genomes_AFR_AF",
+            "gnomAD_genomes_AMR_AC",
+            "gnomAD_genomes_AMR_AN",
+            "gnomAD_genomes_AMR_AF",
+            "gnomAD_genomes_ASJ_AC",
+            "gnomAD_genomes_ASJ_AN",
+            "gnomAD_genomes_ASJ_AF",
+            "gnomAD_genomes_EAS_AC",
+            "gnomAD_genomes_EAS_AN",
+            "gnomAD_genomes_EAS_AF",
+            "gnomAD_genomes_FIN_AC",
+            "gnomAD_genomes_FIN_AN",
+            "gnomAD_genomes_FIN_AF",
+            "gnomAD_genomes_NFE_AC",
+            "gnomAD_genomes_NFE_AN",
+            "gnomAD_genomes_NFE_AF",
+            "gnomAD_genomes_OTH_AC",
+            "gnomAD_genomes_OTH_AN",
+            "gnomAD_genomes_OTH_AF",
+            "clinvar_rs",
+            "clinvar_clnsig",
+            "clinvar_trait",
+            "clinvar_golden_stars",
+            "Interpro_domain",
+            "GTEx_V6p_gene",
+            "GTEx_V6p_tissue"
+          ],
+        },
+      ]
+    },
+    
+    # CADD
+    # https://github.com/ensembl-variation/VEP_plugins/blob/master/CADD.pm
+    # Requires tabix-indexed data file as first param
+    # No other parameters so no form required
+    # data file currently only available for GRCh37
+    {
+      "key" => "CADD",
+      "label" => "CADD",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "helptip" => "Combined Annotation Dependent Depletion (CADD) is a tool for scoring the deleteriousness of single nucleotide variants and insertion/deletion variants in the human genome. CADD integrates multiple annotations into one metric by contrasting variants that survived natural selection with simulated mutations.",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/CADD.pm",
+      "requires_data" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        #"/path/to/whole_genome_SNVs.tsv.gz"
+      ]
+    },
+    
+    # FATHMM-MKL
+    # https://github.com/ensembl-variation/VEP_plugins/blob/master/FATHMM_MKL.pm
+    # Requires tabix-indexed data file as first param
+    # No other parameters so no form required
+    # data file currently only available for GRCh37
+    {
+      "key" => "FATHMM_MKL",
+      "label" => "FATHMM-MKL",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "helptip" => "FATHMM-MKL predicts functional consequences of variants, both coding and non-coding.",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/FATHMM_MKL.pm",
+      "requires_data" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        #"/path/to/fathmm-MKL_Current.tab.gz"
+      ]
+    },
+
+    # GWAVA
+    # https://www.sanger.ac.uk/sanger/StatGen_Gwava
+    # Requires tabix-indexed BED data file from ftp://ftp.sanger.ac.uk/pub/resources/software/gwava/v1.0/VEP_plugin/
+    # data file currently only available for GRCh37
+    {
+      "key" => "Gwava",
+      "label" => "GWAVA",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "helptip" => "Retrieves precomputed Genome Wide Annotation of VAriants (GWAVA) scores for any  variant that overlaps a known variant from the Ensembl variation database",
+      "plugin_url" => "ftp://ftp.sanger.ac.uk/pub/resources/software/gwava/v1.0/VEP_plugin/Gwava.pm",
+      "requires_data" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        "@*",
+        # "/path/to/gwava_scores.bed.gz"
+      ],
+      "form" => [
+        {
+          "name" => "model",
+          "label" => "Model",
+          "type" => "dropdown",
+          "values" => [
+            { "value" => "region",    "caption" => "Region" },
+            { "value" => "tss",       "caption" => "TSS" },
+            { "value" => "unmatched", "caption" => "Unmatched" }
+          ],
+          "value" => "region",
+        },
+      ],
+    },
+
+    # Carol
+    # https://github.com/ensembl-variation/VEP_plugins/blob/master/Carol.pm
+    # Requires Math/CDF Perl module
+    {
+      "key" => "Carol",
+      "helptip" => "Calculates the Combined Annotation scoRing toOL (CAROL) score for a missense mutation based on the pre-calculated SIFT and PolyPhen scores",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/Carol.pm",
+      "requires_install" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+    },
+
+    # Condel
+    # https://github.com/ensembl-variation/VEP_plugins/blob/master/Condel.pm
+    # Requires path to config directory as first param
+    # config directory is checked out as part of VEP_plugins repo, as /[path]/VEP_plugins/config/Condel/config
+    # Within that dir, edit condel_SP.conf so that condel.dir points to /[path]/VEP_plugins/config/Condel
+    {
+      "key" => "Condel",
+      "helptip" => "Calculates the Consensus Deleteriousness (Condel) score for a missense mutation based on the pre-calculated SIFT and PolyPhen scores",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/Condel.pm",
+      "requires_install" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        # "/path/to/config/Condel/config",
+        "@*"
+      ],
+      "form" => [
+        {
+          "name" => "score_pred",
+          "label" => "Score/prediction",
+          "type" => "dropdown",
+          "values" => [
+            { "value" => "b", "caption" => "Prediction and score" },
+            { "value" => "p", "caption" => "Prediction only" },
+            { "value" => "s", "caption" => "Score only" }
+          ],
+          "value" => "b",
+        },
+      ],
+    },
+
+    # LOFTEE
+    # See https://github.com/konradjk/loftee for details
+    {
+      "key" => "LoF",
+      "helptip" => "LOFTEE identifies LoF (loss-of-function) variation",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "plugin_url" => "https://raw.githubusercontent.com/konradjk/loftee/master/LoF.pm",
+      "requires_data" => 1,
+      "requires_install" => 1,
+      "params" => [
+        "@*"
+      ]
+    },
+
+    # LoFtool
+    # Requires LoFtool_scores.txt file as first param (available in VEP_plugins GitHub repo)
+    {
+      "key" => "LoFtool",
+      "helptip" => "Provides a per-gene rank of genic intolerance and consequent susceptibility to disease based on the ratio of Loss-of-function (LoF) to synonymous mutations in ExAC data",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/LoFtool.pm",
+      "requires_data" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        # "/path/to/LoFtool_scores.txt"
+      ]
+    },
+
+    # ExACpLI
+    # Requires ExACpLI_values.txt file as first param (available in VEP_plugins GitHub repo)
+    {
+      "key" => "ExACpLI",
+      "helptip" => "Provides a per-gene probability of being loss-of-function intolerant (pLI) from ExAC data",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/ExACpLI.pm",
+      "requires_data" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        # "/path/to/ExACpLI_values.txt"
+      ]
+    },
+
+    # MPC
+    # Requires fordist_constraint_official_mpc_values.txt.gz data file
+    {
+      "key" => "MPC",
+      "helptip" => "MPC is a missense deleteriousness metric based on the analysis of genic regions depleted of missense mutations in ExAC",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/MPC.pm",
+      "requires_data" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        # "/path/to/fordist_constraint_official_mpc_values.txt.gz"
+      ]
+    },
+
+    # MTR
+    # Requires mtrflatfile_1.0.txt.gz data file from ftp://mtr-viewer.mdhs.unimelb.edu.au/pub
+    {
+      "key" => "MTR",
+      "helptip" => "MTR scores quantify the amount of purifying selection acting specifically on missense variants in a given window of protein-coding sequence",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/MTR.pm",
+      "requires_data" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        # "/path/to/mtrflatfile_1.0.txt.gz"
+      ]
+    },
+
+    # REVEL
+    # Requires data file processed from revel_all_chromosomes.csv.zip
+    {
+      "key" => "REVEL",
+      "helptip" => "An ensemble method for predicting the pathogenicity of rare missense variants",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Pathogenicity predictions",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/REVEL.pm",
+      "requires_data" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        # "/path/to/revel_all_chromosomes.tsv.gz"
+      ]
+    },
+
+
+    
+    ## SPLICING PREDICTIONS
+    #######################
+
+    # dbscSNV
+    {
+      "key" => "dbscSNV",
+      "label" => "dbscSNV",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Splicing predictions",
+      "helptip" => "Retrieves data for splicing variants from a tabix-indexed dbscSNV file",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/dbscSNV.pm",
+      "requires_data" => 1,
+      "requires_install" => 1,
+      "params"  => [
+        #"/path/to/dbscSNV1.1.txt.gz"
+      ],
+      "species" => [
+        "homo_sapiens"
+      ],
+    },
+
+    # GeneSplicer
+    {
+      "key" => "GeneSplicer",
+      "label" => "GeneSplicer",
+      "helptip" => "Detects splice sites in genomic DNA",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Splicing predictions",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/GeneSplicer.pm",
+      "requires_install" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        #"/path/to/genesplicer/bin/linux/genesplicer",
+        #"/path/to/genesplicer/human",
+        "@*"
+      ]
+    },
+
+    # MaxEntScan
+    {
+      "key" => "MaxEntScan",
+      "label" => "MaxEntScan",
+      "helptip" => "Sequence motif and maximum entropy based splice site consensus predictions",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Splicing predictions",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/MaxEntScan.pm",
+      "requires_install" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        #"/path/to/maxentscan"
+      ]
+    },
+
+    # SpliceRegion
+    {
+      "key" => "SpliceRegion",
+      "label" => "SpliceRegion",
+      "helptip" => "More granular predictions of splicing effects",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Splicing predictions",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/SpliceRegion.pm",
+    },
+
+
+    ## CONSERVATION
+    ###############
+
+    # Blosum62
+    {
+      "key" => "Blosum62",
+      "label" => "BLOSUM62",
+      "helptip" => "BLOSUM62 amino acid conservation score",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Conservation",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/Blosum62.pm",
+    },
+
+    # Conservation
+    # Use the following query to get valid species sets:
+    #
+    # SELECT group_concat(concat("_stt_", gd.name) SEPARATOR ' '), REPLACE(mlss.name, "Gerp Conservation Scores ", ""), sst.value
+    #   FROM method_link ml, 
+    #     method_link_species_set mlss, 
+    #     genome_db gd, species_set ss, species_set_tag sst
+    #   WHERE mlss.method_link_id = ml.method_link_id AND
+    #     mlss.species_set_id = ss.species_set_id AND 
+    #     ss.genome_db_id = gd.genome_db_id AND
+    #     ss.species_set_id = sst.species_set_id AND
+    #     (ml.class = "ConservationScore.conservation_score")
+    #   GROUP BY mlss.species_set_id
+    {
+      "key" => "Conservation",
+      "helptip" => "Retrieves a conservation score from the Ensembl Compara databases for variant positions",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Conservation",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/Conservation.pm",
+      "params" => [
+        "@*"
+      ],
+      "form" => [
+        {
+          "name" => "method_link_type",
+          "label" => "Method",
+          "type" => "dropdown",
+          "values" => [
+            { "value" => "GERP_CONSERVATION_SCORE", "caption" => "GERP"}
+          ]
+        },
+        {
+          "name" => "species_set",
+          "label" => "Species set",
+          "type" => "dropdown",
+          "values" => [
+            { "value" => "mammals",    "caption" => "39 eutherian mammals"   }, #"class" => "_stt_macaca_mulatta _stt_echinops_telfairi _stt_tupaia_belangeri _stt_erinaceus_europaeus _stt_sorex_araneus _stt_microcebus_murinus _stt_pongo_abelii _stt_equus_caballus _stt_ochotona_princeps _stt_cavia_porcellus _stt_choloepus_hoffmanni _stt_procavia_capensis _stt_tursiops_truncatus _stt_tarsius_syrichta _stt_dipodomys_ordii _stt_vicugna_pacos _stt_pteropus_vampyrus _stt_loxodonta_africana _stt_oryctolagus_cuniculus _stt_ailuropoda_melanoleuca _stt_nomascus_leucogenys _stt_callithrix_jacchus _stt_myotis_lucifugus _stt_bos_taurus _stt_gorilla_gorilla _stt_otolemur_garnettii _stt_pan_troglodytes _stt_ictidomys_tridecemlineatus _stt_sus_scrofa _stt_mus_musculus _stt_canis_familiaris _stt_mustela_putorius_furo _stt_felis_catus _stt_ovis_aries _stt_dasypus_novemcinctus _stt_homo_sapiens _stt_papio_anubis _stt_chlorocebus_sabaeus _stt_rattus_norvegicus" },
+            { "value" => "amniotes",   "caption" => "23 amniota vertebrates" }, #"class" => "_stt_macaca_mulatta _stt_ornithorhynchus_anatinus _stt_monodelphis_domestica _stt_pongo_abelii _stt_equus_caballus _stt_taeniopygia_guttata _stt_oryctolagus_cuniculus _stt_anolis_carolinensis _stt_meleagris_gallopavo _stt_callithrix_jacchus _stt_bos_taurus _stt_gorilla_gorilla _stt_pan_troglodytes _stt_sus_scrofa _stt_mus_musculus _stt_canis_familiaris _stt_felis_catus _stt_gallus_gallus _stt_ovis_aries _stt_homo_sapiens _stt_papio_anubis _stt_chlorocebus_sabaeus _stt_rattus_norvegicus" },
+            { "value" => "sauropsids", "caption" => "7 sauropsids"           }, #"class" => "_stt_taeniopygia_guttata _stt_anolis_carolinensis _stt_meleagris_gallopavo _stt_pelodiscus_sinensis _stt_gallus_gallus _stt_anas_platyrhynchos _stt_ficedula_albicollis" },
+            { "value" => "fish",       "caption" => "11 fish"                }, #"class" => "_stt_takifugu_rubripes _stt_gasterosteus_aculeatus _stt_oryzias_latipes _stt_tetraodon_nigroviridis _stt_gadus_morhua _stt_oreochromis_niloticus _stt_xiphophorus_maculatus _stt_astyanax_mexicanus _stt_lepisosteus_oculatus _stt_poecilia_formosa _stt_danio_rerio" },
+          ]
+        },
+      ]
+    },
+
+    # AncestralAllele
+    # Requires processed FASTA file from ftp://ftp.ensembl.org/pub/current_fasta/ancestral_alleles/
+    {
+      "key" => "AncestralAllele",
+      "label" => "Ancestral allele",
+      "helptip" => "Retrieves the ancestral allele for variants inferred from the Ensembl Compara Enredo-Pecan-Ortheus (EPO) pipeline",
+      "available" => 0,
+      "enabled" => 0,
+      "section" => "Conservation",
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/AncestralAllele.pm",
+      "requires_data" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        # "/path/to/homo_sapiens_ancestor_GRCh38_e93.fa.gz"
+      ]
+    },
+
+
+    ## FREQUENCY DATA
+    #################
+
+    # ExAC
+    {
+      "key" => "ExAC",
+      "label" => "ExAC frequencies",
+      "helptip" => "Reports allele frequencies from the Exome Aggregation Consortium",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/ExAC.pm",
+      "section" => "Frequency data",
+      "requires_data" => 1,
+      "species" => [
+        "homo_sapiens"
+      ],
+      "params" => [
+        # "/path/to/ExAC.r0.3.sites.vep.vcf.gz"
+      ]
+    },
+
+
+    ## OTHER
+    ########
+
+    # CSN
+    {
+      "key" => "CSN",
+      "helptip" => "Reports Clinical Sequencing Nomenclature (CSN) for variants",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/CSN.pm",
+    },
+
+    # miRNA
+    {
+      "key" => "miRNA",
+      "label" => "miRNA structure",
+      "helptip" => "Determines where in the secondary structure of a miRNA a variant falls",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/miRNA.pm",
+    },
+    
+
+
+    # NearestGene
+    {
+      "key" => "NearestGene",
+      "label" => "Nearest gene",
+      "helptip" => "Finds the nearest gene to non-genic variants",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/NearestGene.pm",
+    },
+
+    # LD
+    {
+      "key" => "LD",
+      "label" => "Linkage disequilibrium",
+      "helptip" => "Finds variants in linkage disequilibrium with any overlapping existing variants from the Ensembl variation databases",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/LD.pm",
+      "section" => "Variant data",
+      "params" => [
+        "@*"
+      ],
+      "form" => [
+        {
+          "name" => "population",
+          "label" => "Population",
+          "type" => "dropdown",
+          "values" => [
+            { "value" => "1000GENOMES:phase_3:ACB", "caption" => "African Caribbean in Barbados" },
+            { "value" => "1000GENOMES:phase_3:ASW", "caption" => "African Ancestry in Southwest US" },
+            { "value" => "1000GENOMES:phase_3:BEB", "caption" => "Bengali in Bangladesh" },
+            { "value" => "1000GENOMES:phase_3:CDX", "caption" => "Chinese Dai in Xishuangbanna, China" },
+            { "value" => "1000GENOMES:phase_3:CEU", "caption" => "Utah residents with Northern and Western European ancestry" },
+            { "value" => "1000GENOMES:phase_3:CHB", "caption" => "Han Chinese in Bejing, China" },
+            { "value" => "1000GENOMES:phase_3:CHS", "caption" => "Southern Han Chinese, China" },
+            { "value" => "1000GENOMES:phase_3:CLM", "caption" => "Colombian in Medellin, Colombia" },
+            { "value" => "1000GENOMES:phase_3:ESN", "caption" => "Esan in Nigeria" },
+            { "value" => "1000GENOMES:phase_3:FIN", "caption" => "Finnish in Finland" },
+            { "value" => "1000GENOMES:phase_3:GBR", "caption" => "British in England and Scotland" },
+            { "value" => "1000GENOMES:phase_3:GIH", "caption" => "Gujarati Indian in Houston, TX" },
+            { "value" => "1000GENOMES:phase_3:IBS", "caption" => "Iberian populations in Spain" },
+            { "value" => "1000GENOMES:phase_3:ITU", "caption" => "Indian Telugu in the UK" },
+            { "value" => "1000GENOMES:phase_3:JPT", "caption" => "Japanese in Tokyo, Japan" },
+            { "value" => "1000GENOMES:phase_3:KHV", "caption" => "Kinh in Ho Chi Minh City, Vietnam" },
+            { "value" => "1000GENOMES:phase_3:LWK", "caption" => "Luhya in Webuye, Kenya" },
+            { "value" => "1000GENOMES:phase_3:MAG", "caption" => "Mandinka in The Gambia" },
+            { "value" => "1000GENOMES:phase_3:MSL", "caption" => "Mende in Sierra Leone" },
+            { "value" => "1000GENOMES:phase_3:MXL", "caption" => "Mexican Ancestry in Los Angeles, California" },
+            { "value" => "1000GENOMES:phase_3:PEL", "caption" => "Peruvian in Lima, Peru" },
+            { "value" => "1000GENOMES:phase_3:PJL", "caption" => "Punjabi in Lahore, Pakistan" },
+            { "value" => "1000GENOMES:phase_3:PUR", "caption" => "Puerto Rican in Puerto Rico" },
+            { "value" => "1000GENOMES:phase_3:STU", "caption" => "Sri Lankan Tamil in the UK" },
+            { "value" => "1000GENOMES:phase_3:TSI", "caption" => "Toscani in Italy" },
+            { "value" => "1000GENOMES:phase_3:YRI", "caption" => "Yoruba in Ibadan, Nigeria" },
+          ],
+          "value" => "1000GENOMES:phase_3:CEU",
+        },
+        {
+          "name" => "threshold",
+          "label" => "r2 cutoff",
+          "type" => "string",
+          "value" => 0.8,
+        },
+      ]
+    },
+
+    # SameCodon
+    {
+      "key" => "SameCodon",
+      "label" => "Variants in same codon",
+      "helptip" => "Reports existing variants that fall in the same codon",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/SameCodon.pm",
+      "section" => "Variant data",
+    },
+    # LOVD
+    {
+      "key" => "LOVD",
+      "label" => "LOVD",
+      "helptip" => "Retrieves LOVD variation data",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/LOVD.pm",
+      "section" => "Variant data",
+    },
+
+    # GO
+    {
+      "key" => "GO",
+      "label" => "Gene Ontology",
+      "helptip" => "Retrieves Gene Ontology terms associated with transcripts/translations via the Ensembl API",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/GO.pm",
+      "section" => "Gene data",
+    },
+
+    # Downstream
+    {
+      "key" => "Downstream",
+      "label" => "Downstream",
+      "helptip" => "Predicts the downstream effects of a frameshift variant on the protein sequence of a transcript",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/Downstream.pm",
+    },
+
+    # ProteinSeqs
+    {
+      "key" => "ProteinSeqs",
+      "label" => "Protein sequences",
+      "helptip" => "Prints out the reference and mutated protein sequences of any proteins found with non-synonymous mutations",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/ProteinSeqs.pm",
+    },
+
+    # TSSDistance
+    {
+      "key" => "TSSDistance",
+      "label" => "TSS distance",
+      "helptip" => "Calculates the distance from the transcription start site for upstream variants   ",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/TSSDistance.pm",
+    },
+    
+    # Phenotypes
+    {
+      "key" => "Phenotypes",
+      "label" => "Phenotypes",
+      "helptip" => "Retrieves overlapping phenotype annotations",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/Phenotypes.pm",
+    },    
+    # Draw
+    {
+      "key" => "Draw",
+      "label" => "Draw",
+      "helptip" => "Creates images of the transcript model showing variant location",
+      "available" => 0,
+      "enabled" => 0,
+      "requires_install" => 1,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/Draw.pm",
+    },
+    # G2P
+    {
+      "key" => "G2P",
+      "label" => "G2P",
+      "helptip" => "Assesses variants using G2P allelic requirements for potential phenotype involvement.",
+      "available" => 0,
+      "enabled" => 0,
+      "requires_data" => 1,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/G2P.pm",
+    },
+
+    # LocalID
+    {
+      "key" => "LocalID",
+      "label" => "LocalID",
+      "helptip" => "Allows you to use variant IDs as VEP input without making a database connection.",
+      "available" => 0,
+      "enabled" => 0,
+      "plugin_url" => "https://raw.githubusercontent.com/Ensembl/VEP_plugins/release/94/LocalID.pm",
+    },
+
+    
+  ]
+};

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/vep.xml	Mon Jul 15 05:17:17 2019 -0400
@@ -0,0 +1,563 @@
+<tool id="vep" name="Vep" version="0.1.0">
+    <requirements>
+        <requirement type="package" version="94.5">ensembl-vep</requirement>
+    </requirements>
+    <command detect_errors="exit_code"><![CDATA[
+        #if str( $species.fields.type ) == "refseq":
+            #set $cache_type = "--refseq"
+        #elif str( $species.fields.type ) == "merged":
+            #set $cache_type = "--merged"
+        #else:
+            #set $cache_type = ""
+        #end if
+
+        #if $output_options.cell_type.strip():
+            #set $cell_type = '--cell_type ' + str( $output_options.cell_type )
+        #else:
+            #set $cell_type = ''
+        #end if
+
+        #if str( $output_options.individual.select ) == "all":
+            #set $individual = '--individual all'
+        #elif str( $output_options.individual.select ) == "ind":
+            #set $individual = '--individual ind ' + str($output_options.individual.list)
+        #else:
+            #set $individual = ''
+        #end if 
+
+        #if str( $output_options.vcf_info_field.select ) == "other":
+            #set $vcf_info_field = '--vcf_info_field ' + str( $output_options.vcf_info_field.name )
+        #else
+            #set $vcf_info_field = '--vcf_info_field ' + str( $output_options.vcf_info_field.select )
+        #end if
+
+        #if str( $identifier_options.synonyms.select ) == "yes":
+            #set $synonyms = '--synonyms ' + str( $identifier_options.synonyms.file )
+        #else
+            #set $synonyms = ''
+        #end if
+
+        #if str( $filtering_qc.transcript_filter.select ) == "yes":
+            #set $transcript_filter = '--transcript_filter "' + str( $filtering_qc.transcript_filter.filter ) + '"'
+        #else:
+            #set $transcript_filter = ''
+        #end if
+
+        #if str( $filtering_qc.chr.select ) == "yes":
+            #set chr = '--chr ' + str( $filtering_qc.chr.list )
+        #else:
+            #set chr = ''
+        #end if
+
+        #if str( $filtering_qc.pick_order.select ) == "yes":
+            #set $pick_order = '--pick_order ' + str( $filtering_qc.pick_order.list )
+        #else:
+            #set $pick_order = ''
+        #end if
+
+        #if str( $filtering_qc.freq.select ) == "yes":
+            #set $freq_pop = str( $filtering_qc.freq.freq_pop )
+            #set $freq_freq = str( $filtering_qc.freq.freq_freq )
+            #set $freq_gt_lt = str( $filtering_qc.freq.freq_gt_lt )
+            #set $freq_filter = str( $filtering_qc.freq.freq_filter )
+            #set $freq = $freq_pop + ' --freq_freq ' + $freq_freq + ' ' + $freq_gt_lt + ' ' + $freq_filter
+        #else:
+            #set $freq = ''
+        #end if
+
+        vep 
+        --format vcf 
+        --VCF
+        --no_stats
+        --dir_plugins $__tool_directory__/dir_plugins
+        --cache
+        --dir_cache ${species.fields.path}
+        --force_overwrite
+        --species ${species.fields.dbkey}
+        $cache_type
+        --input_file "$input" 
+        --output_file "$output"
+        $offline
+        $output_options.variant_class
+        $output_options.sift
+        $output_options.polyphen
+        $output_options.humdiv
+        $output_options.nearest
+        --distance $output_options.distance
+        $output_options.gene_phenotype
+        $output_options.regulatory
+        $cell_type
+        $individual
+        $vcf_info_field
+        $output_options.phased
+        $output_options.total_length
+        $output_options.numbers
+        $output_options.domains
+        $output_options.no_escape
+        $output_options.keep_csq
+        --terms $output_options.terms
+        $output_options.no_headers
+        $identifier_options.transcript_version
+        $identifier_options.protein
+        $identifier_options.symbol
+        $identifier_options.ccds
+        $identifier_options.tsl
+        $identifier_options.appris
+        $identifier_options.canonical
+        $identifier_options.biotype
+        $identifier_options.xref_refseq
+        $synonyms
+        $co_located_variants_options.check_existing
+        $co_located_variants_options.exclude_null_alleles
+        $co_located_variants_options.no_check_alleles
+        $co_located_variants_options.af
+        $co_located_variants_options.max_af
+        $co_located_variants_options.af_1kg
+        $co_located_variants_options.af_esp
+        $co_located_variants_options.af_gnomad
+        $co_located_variants_options.af_exac
+        $co_located_variants_options.pubmed
+        $co_located_variants_options.failed
+        $filtering_qc.gencode_basic
+        $filtering_qc.all_refseq
+        $filtering_qc.exclude_predicted
+        $transcript_filter
+        $filtering_qc.check_ref
+        $filtering_qc.lookup_ref
+        $chr
+        $filtering_qc.dont_skip
+        $filtering_qc.allow_non_variant
+        $filtering_qc.coding_only
+        $filtering_qc.no_intergenic
+        $filtering_qc.pick
+        $filtering_qc.pick_allele
+        $filtering_qc.pick_allele_gene
+        $filtering_qc.per_gene
+        $filtering_qc.flag_pick
+        $filtering_qc.flag_pick_allele
+        $filtering_qc.flag_pick_allele_gene
+        $pick_order
+        $filtering_qc.most_severe
+        $filtering_qc.summary
+        $filtering_qc.filter_common
+        $freq
+        #for $i, $s in enumerate( $other_anotations.plugins )
+            --plugin $s.plugin
+        #end for
+    ]]></command>
+    <inputs>
+        <param type="data" name="input" format="vcf" />
+        <param name="species" type="select">
+            <options from_data_table="vep_cache_data">
+                <validator type="no_options" message="Run the data manager to fetch cache data"/>
+            </options>
+        </param>
+        <param name="offline" type="select">
+                <option value="--offline">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+        <section name="output_options" title="Output options">
+            <param name="variant_class" type="select">
+                <option value="--variant_class">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="sift" type="select">
+                <option value="--sift p">Prediction</option>
+                <option value="--sift s">Score</option>
+                <option value="--sift b">Both</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="polyphen" type="select">
+                <option value="--polyphen p">Prediction</option>
+                <option value="--polyphen s">Score</option>
+                <option value="--polyphen b">Both</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="humdiv" type="select">
+                <option value="--humdiv">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="nearest" type="select">
+                <option value="--nearest transcript">Transcript</option>
+                <option value="--nearest gene">Gene</option>
+                <option value="--nearest symbol">Symbol</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="distance" type="text" value="5000">
+                <validator type="regex" message="Has to be a number">\d+(,\d+)?</validator>
+            </param>
+            <param name="gene_phenotype" type="select">
+                <option value="--gene_phenotype">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="regulatory" type="select">
+                <option value="--regulatory">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="cell_type" type="text"/>
+            <conditional name="individual">
+                <param name="select" type="select" label="individual">
+                    <option value="all">All</option>
+                    <option value="ind">Individual/List</option>
+                    <option value="no" selected="true">No</option>
+                </param>
+                <when value="ind">
+                    <param name="list" type="text" />
+                </when>
+            </conditional>
+
+            <param name="phased" type="select">
+                <option value="--phased">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="total_length" type="select">
+                <option value="--total_length">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="numbers" type="select">
+                <option value="--numbers">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="domains" type="select">
+                <option value="--domains">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="no_escape" type="select">
+                <option value="--no_escape">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="keep_csq" type="select">
+                <option value="--no_escape">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <conditional name="vcf_info_field">
+                <param name="select" type="select" label="vcf_info_field">
+                    <option value="CSQ" selected="true">CSQ</option>
+                    <option value="ANN">ANN</option>
+                    <option value="other">Other</option>
+                </param>
+                <when value="other">
+                    <param name="name" type="text" />
+                </when>
+            </conditional>
+            <param name="terms" type="select">
+                <option value="SO" selected="true">SO</option>
+                <option value="display">display</option>
+                <option value="NCBI">NCBI</option>
+            </param>
+            <param name="no_headers" type="select">
+                <option value="--no_headers">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+        </section>
+
+        <section name="identifier_options" title="Identifiers options">
+            <!-- TODO add hgvs -->
+            <!-- TODO add hgvsg -->
+            <!-- TODO add shift_hgvs -->
+            <param name="transcript_version" type="select">
+                <option value="--transcript_version">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="protein" type="select">
+                <option value="--protein">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="symbol" type="select">
+                <option value="--symbol">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="ccds" type="select">
+                <option value="--ccds">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="tsl" type="select">
+                <option value="--tsl">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="appris" type="select">
+                <option value="--appris">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="canonical" type="select">
+                <option value="--canonical">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="biotype" type="select">
+                <option value="--biotype">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="xref_refseq" type="select">
+                <option value="--xref_refseq">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <conditional name="synonyms">
+                <param name="select" type="select" label="synonyms">
+                    <option value="yes">Yes</option>
+                    <option value="no" selected="true">No</option>
+                </param>
+                <when value="yes">
+                    <param type="data" name="file" format="tabular" />
+                </when>
+            </conditional>
+        </section>
+
+        <section name="co_located_variants_options" title="Co-located variants options">
+            <param name="check_existing" type="select">
+                <option value="--check_existing">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="exclude_null_alleles" type="select">
+                <option value="--exclude_null_alleles">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="no_check_alleles" type="select">
+                <option value="--no_check_alleles">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="af" type="select">
+                <option value="--af">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="max_af" type="select">
+                <option value="--max_af">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="af_1kg" type="select">
+                <option value="--af_1kg">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="af_esp" type="select">
+                <option value="--af_esp">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="af_gnomad" type="select">
+                <option value="--af_gnomad">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="af_exac" type="select">
+                <option value="--af_exac">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="pubmed" type="select">
+                <option value="--pubmed">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="failed" type="select">
+                <option value="--failed 1">Yes</option>
+                <option value="--failed 0" selected="true">No</option>
+            </param>
+        </section>
+
+        <section name="filtering_qc" title="Filtering and QC">
+            <param name="gencode_basic" type="select">
+                <option value="--gencode_basic">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="all_refseq" type="select">
+                <option value="--all_refseq">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="exclude_predicted" type="select">
+                <option value="--exclude_predicted">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <conditional name="transcript_filter">
+                <param name="select" type="select" label="transcript_filter">
+                    <option value="yes">Yes</option>
+                    <option value="no" selected="true">No</option>
+                </param>
+                <when value="yes">
+                    <param type="text" name="filter">
+                        <sanitizer>
+                            <valid initial="string.printable">
+                                <remove value="&apos;" />
+                            </valid>
+                        </sanitizer>
+                    </param>
+                </when>
+            </conditional>
+            <param name="check_ref" type="select">
+                <option value="--check_ref">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="lookup_ref" type="select">
+                <option value="--lookup_ref">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <conditional name="chr">  <!-- TODO double check, looks correct but doesn't seem to work -->
+                <param name="select" type="select" label="chr">
+                    <option value="yes">Yes</option>
+                    <option value="no" selected="true">No</option>
+                </param>
+                <when value="yes">
+                    <param type="text" name="list" />
+                </when>
+            </conditional>
+            <param name="dont_skip" type="select">
+                <option value="" selected="true">Yes</option>
+                <option value="--dont_skip">No</option>
+            </param>
+            <param name="allow_non_variant" type="select">
+                <option value="--allow_non_variant">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="coding_only" type="select">
+                <option value="--coding_only">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="no_intergenic" type="select">
+                <option value="--no_intergenic">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="pick" type="select">
+                <option value="--pick">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="pick_allele" type="select">
+                <option value="--pick_allele">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="pick_allele_gene" type="select">
+                <option value="--pick_allele_gene">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="per_gene" type="select">
+                <option value="--per_gene">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="flag_pick" type="select">
+                <option value="--flag_pick">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="flag_pick_allele" type="select">
+                <option value="--flag_pick_allele">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="flag_pick_allele_gene" type="select">
+                <option value="--flag_pick_allele_gene">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <conditional name="pick_order">
+                <param name="select" type="select" label="pick_order">
+                    <option value="yes">Yes</option>
+                    <option value="no" selected="true">No</option>
+                </param>
+                <when value="yes">
+                    <param type="text" name="list" />
+                </when>
+            </conditional>
+            <param name="most_severe" type="select">
+                <option value="--most_severe">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="summary" type="select"> <!-- TODO double check, looks correct but doesn't seem to work -->
+                <option value="--summary">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+            <param name="filter_common" type="select">
+                <option value="--filter_common">Yes</option>
+                <option value="" selected="true">No</option>
+            </param>
+
+            <conditional name="freq">
+                <param name="select" type="select" label="freq">
+                    <option value="yes">Yes</option>
+                    <option value="no" selected="true">No</option>
+                </param>
+                <when value="yes">
+                    <param name="freq_pop" type="select">
+                        <option value="--freq_pop 1KG_ALL">1000 genomes combined population (global)</option>
+                        <option value="--freq_pop 1KG_AFR">1000 genomes combined African population</option>
+                        <option value="--freq_pop 1KG_AMR">1000 genomes combined American population</option>
+                        <option value="--freq_pop 1KG_EAS">1000 genomes combined East Asian population</option>
+                        <option value="--freq_pop 1KG_EUR">1000 genomes combined European population</option>
+                        <option value="--freq_pop 1KG_SAS">1000 genomes combined South Asian population</option>
+                        <option value="--freq_pop ESP_AA">NHLBI-ESP African American</option>
+                        <option value="--freq_pop ESP_EA">NHLBI-ESP European American</option>
+                        <option value="--freq_pop gnomAD">gnomAD combined population</option>
+                        <option value="--freq_pop gnomAD_AFR">gnomAD African/African American population</option>
+                        <option value="--freq_pop gnomAD_AMR">gnomAD Latino population</option>
+                        <option value="--freq_pop gnomAD_ASJ">gnomAD Ashkenazi Jewish population</option>
+                        <option value="--freq_pop gnomAD_EAS">gnomAD East Asian population</option>
+                        <option value="--freq_pop gnomAD_FIN">gnomAD Finnish population</option>
+                        <option value="--freq_pop gnomAD_NFE">gnomAD non-Finnish European population</option>
+                        <option value="--freq_pop gnomAD_OTH">gnomAD other population</option>
+                        <option value="--freq_pop gnomAD_SAS">gnomAD South Asian population</option>
+                    </param>
+                    <param type="text" name="freq_freq" />
+                    <param name="freq_gt_lt" type="select">
+                        <option value="--freq_gt_lt gt" selected="true">Greater</option>
+                        <option value="--freq_gt_lt lt">Less than</option>
+                    </param>
+                    <param name="freq_filter" type="select">
+                        <option value="--freq_filter include" selected="true">Include</option>
+                        <option value="--freq_gt_lt exclude">Exclude</option>
+                    </param>
+                </when>
+            </conditional>
+            
+            <!-- TODO add check_frequency group -->
+        </section>
+
+         <section name="other_anotations" title="Other anotations">
+            <repeat name="plugins" title="Plugins" min="0" default="0">
+                <param name="plugin" type="select" label="Plugin">
+                    <option value="AncestralAllele">AncestralAllele</option>
+                    <option value="Blosum62">Blosum62</option>
+                    <option value="CADD">CADD</option>
+                    <option value="Carol">Carol</option>
+                    <option value="CCDSFilter">CCDSFilter</option>
+                    <option value="Condel">Condel</option>
+                    <option value="Conservation">Conservation</option>
+                    <option value="CSN">CSN</option>
+                    <option value="DAS">DAS</option>
+                    <option value="dbNSFP">dbNSFP</option>
+                    <option value="dbscSNV">dbscSNV</option>
+                    <option value="Downstream">Downstream</option>
+                    <option value="Draw">Draw</option>
+                    <option value="ExACpLI">ExACpLI</option>
+                    <option value="ExAC">ExAC</option>
+                    <option value="FATHMM_MKL">FATHMM_MKL</option>
+                    <option value="FATHMM">FATHMM</option>
+                    <option value="G2P">G2P</option>
+                    <option value="GeneSplicer">GeneSplicer</option>
+                    <option value="GO">GO</option>
+                    <option value="GXA">GXA</option>
+                    <option value="HGVSReferenceBase">HGVSReferenceBase</option>
+                    <option value="LD">LD</option>
+                    <option value="LocalID">LocalID</option>
+                    <option value="LoFtool">LoFtool</option>
+                    <option value="LOVD">LOVD</option>
+                    <option value="MaxEntScan">MaxEntScan</option>
+                    <option value="miRNA">miRNA</option>
+                    <option value="MPC">MPC</option>
+                    <option value="MTR">MTR</option>
+                    <option value="NearestGene">NearestGene</option>
+                    <option value="NonSynonymousFilter">NonSynonymousFilter</option>
+                    <option value="Phenotypes">Phenotypes</option>
+                    <option value="PolyPhen_SIFT">PolyPhen_SIFT</option>
+                    <option value="PON_P2">PON_P2</option>
+                    <option value="ProteinSeqs">ProteinSeqs</option>
+                    <option value="RankFilter">RankFilter</option>
+                    <option value="RefSeqHGVS">RefSeqHGVS</option>
+                    <option value="REVEL">REVEL</option>
+                    <option value="SameCodon">SameCodon</option>
+                    <option value="SpliceRegion">SpliceRegion</option>
+                    <option value="SubsetVCF">SubsetVCF</option>
+                    <option value="TSSDistance">TSSDistance</option>
+                    <option value="Wildtype">Wildtype</option>
+                </param>
+            </repeat>
+        </section>
+        
+        
+        
+    </inputs>
+    <outputs>
+        <data name="output" format="vcf" />
+    </outputs>
+    <help><![CDATA[
+        This is a straightforward tool wrapper for VEP, for more information about these parameters visit the VEP documentation: https://www.ensembl.org/info/docs/tools/vep/script/vep_options.html
+    ]]></help>
+</tool>
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