|
0
|
1 =head1 LICENSE
|
|
|
2
|
|
|
3 Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
|
|
|
4 Copyright [2016-2018] EMBL-European Bioinformatics Institute
|
|
|
5
|
|
|
6 Licensed under the Apache License, Version 2.0 (the "License");
|
|
|
7 you may not use this file except in compliance with the License.
|
|
|
8 You may obtain a copy of the License at
|
|
|
9
|
|
|
10 http://www.apache.org/licenses/LICENSE-2.0
|
|
|
11
|
|
|
12 Unless required by applicable law or agreed to in writing, software
|
|
|
13 distributed under the License is distributed on an "AS IS" BASIS,
|
|
|
14 WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
|
|
|
15 See the License for the specific language governing permissions and
|
|
|
16 limitations under the License.
|
|
|
17
|
|
|
18 =head1 CONTACT
|
|
|
19
|
|
|
20 Ensembl <http://www.ensembl.org/info/about/contact/index.html>
|
|
|
21
|
|
|
22 =cut
|
|
|
23
|
|
|
24 =head1 NAME
|
|
|
25
|
|
|
26 MPC
|
|
|
27
|
|
|
28 =head1 SYNOPSIS
|
|
|
29
|
|
|
30 mv MPC.pm ~/.vep/Plugins
|
|
|
31 ./vep -i variations.vcf --plugin MPC,fordist_constraint_official_mpc_values.txt.gz
|
|
|
32
|
|
|
33 =head1 DESCRIPTION
|
|
|
34
|
|
|
35 A VEP plugin that retrieves MPC scores for variants from a tabix-indexed MPC data file.
|
|
|
36
|
|
|
37 MPC is a missense deleteriousness metric based on the analysis of genic regions
|
|
|
38 depleted of missense mutations in the Exome Agggregation Consortium (ExAC) data.
|
|
|
39
|
|
|
40 The MPC score is the product of work by Kaitlin Samocha (ks20@sanger.ac.uk).
|
|
|
41 Publication currently in pre-print: Samocha et al bioRxiv 2017 (TBD)
|
|
|
42
|
|
|
43 The MPC score file is available to download from:
|
|
|
44
|
|
|
45 ftp://ftp.broadinstitute.org/pub/ExAC_release/release1/regional_missense_constraint/
|
|
|
46
|
|
|
47 The data are currently mapped to GRCh37 only. Not all transcripts are included; see
|
|
|
48 README in the above directory for exclusion criteria.
|
|
|
49
|
|
|
50 =cut
|
|
|
51
|
|
|
52 package MPC;
|
|
|
53
|
|
|
54 use strict;
|
|
|
55 use warnings;
|
|
|
56
|
|
|
57 use Bio::EnsEMBL::Utils::Sequence qw(reverse_comp);
|
|
|
58
|
|
|
59 use Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin;
|
|
|
60
|
|
|
61 use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepTabixPlugin);
|
|
|
62
|
|
|
63 my %INCLUDE_SO = map {$_ => 1} qw(missense_variant stop_lost stop_gained start_lost);
|
|
|
64
|
|
|
65 sub new {
|
|
|
66 my $class = shift;
|
|
|
67
|
|
|
68 my $self = $class->SUPER::new(@_);
|
|
|
69
|
|
|
70 $self->expand_left(0);
|
|
|
71 $self->expand_right(0);
|
|
|
72
|
|
|
73 $self->get_user_params();
|
|
|
74
|
|
|
75 return $self;
|
|
|
76 }
|
|
|
77
|
|
|
78 sub feature_types {
|
|
|
79 return ['Transcript'];
|
|
|
80 }
|
|
|
81
|
|
|
82 sub get_header_info {
|
|
|
83 return { MPC => 'MPC score' };
|
|
|
84 }
|
|
|
85
|
|
|
86 sub run {
|
|
|
87 my ($self, $tva) = @_;
|
|
|
88
|
|
|
89 # only for missense variants
|
|
|
90 return {} unless grep {$INCLUDE_SO{$_->SO_term}} @{$tva->get_all_OverlapConsequences};
|
|
|
91
|
|
|
92 my $vf = $tva->variation_feature;
|
|
|
93
|
|
|
94 return {} unless $vf->{start} eq $vf->{end};
|
|
|
95
|
|
|
96 # get allele, reverse comp if needed
|
|
|
97 my $allele = $tva->variation_feature_seq;
|
|
|
98 reverse_comp(\$allele) if $vf->{strand} < 0;
|
|
|
99
|
|
|
100 return {} unless $allele =~ /^[ACGT]$/;
|
|
|
101
|
|
|
102 # get transcript stable ID
|
|
|
103 my $tr_id = $tva->transcript->stable_id;
|
|
|
104
|
|
|
105 my ($res) = grep {
|
|
|
106 $_->{pos} == $vf->{start} &&
|
|
|
107 $_->{alt} eq $allele &&
|
|
|
108 $_->{tr} eq $tr_id
|
|
|
109 } @{$self->get_data($vf->{chr}, $vf->{start}, $vf->{end})};
|
|
|
110
|
|
|
111 return $res ? { MPC => $res->{MPC} } : {};
|
|
|
112 }
|
|
|
113
|
|
|
114 sub parse_data {
|
|
|
115 my ($self, $line) = @_;
|
|
|
116
|
|
|
117 my @split = split /\t/, $line;
|
|
|
118
|
|
|
119 return {
|
|
|
120 pos => $split[1],
|
|
|
121 alt => $split[3],
|
|
|
122 tr => $split[5],
|
|
|
123 MPC => $split[-1],
|
|
|
124 };
|
|
|
125 }
|
|
|
126
|
|
|
127 sub get_start {
|
|
|
128 return $_[1]->{pos};
|
|
|
129 }
|
|
|
130
|
|
|
131 sub get_end {
|
|
|
132 return $_[1]->{pos};
|
|
|
133 }
|
|
|
134
|
|
|
135 1;
|
