diff dir_plugins/Conservation.pm @ 3:49397129aec0 draft

Uploaded

--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/dir_plugins/Conservation.pm	Mon Jul 15 05:20:39 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;
+