=head1 LICENSE Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute Copyright [2016-2022] 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 =cut =head1 NAME REVEL =head1 SYNOPSIS mv REVEL.pm ~/.vep/Plugins ./vep -i variations.vcf --assembly GRCh37 --plugin REVEL,/path/to/revel/data.tsv.gz ./vep -i variations.vcf --assembly GRCh38 --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 The plugin supports several REVEL file versions: - REVEL file version Dec 2017, which has 7 columns and only GRCh37 coordinates - REVEL file version Feb 2020, which has 8 columns with GRCh37 and GRCh38 coordinates - REVEL file version May 2021, which has 9 columns with GRCh37 and GRCh38 coordinates and a new column with transcript ids These files can be tabix-processed by: Unzip revel-v1.3_all_chromosomes.zip cat revel_with_transcript_ids | tr "," "\t" > tabbed_revel.tsv sed '1s/.*/#&/' tabbed_revel.tsv > new_tabbed_revel.tsv bgzip new_tabbed_revel.tsv for GRCh37: tabix -f -s 1 -b 2 -e 2 new_tabbed_revel.tsv.gz for GRCh38: zcat new_tabbed_revel.tsv.gz | head -n1 > h zgrep -h -v ^#chr new_tabbed_revel.tsv.gz | awk '$3 != "." ' | sort -k1,1 -k3,3n - | cat h - | bgzip -c > new_tabbed_revel_grch38.tsv.gz tabix -f -s 1 -b 3 -e 3 new_tabbed_revel_grch38.tsv.gz The tabix utility must be installed in your path to use this plugin. The --assembly flag is required 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(); # get column count in REVEL file from header line my $file = $self->params->[0]; $self->add_file($file); open HEAD, "tabix -fh $file 1:1-1 2>&1 | "; while() { next unless /^\#/; chomp; $_ =~ s/^\#//; $self->{headers} = [split]; } close HEAD; die "ERROR: Could not read headers from $file\n" unless defined($self->{headers}) && scalar @{$self->{headers}}; my $column_count = scalar @{$self->{headers}}; if ($column_count != 7 && $column_count != 8 && $column_count != 9) { die "ERROR: Column count must be 8 or 9 for REVEL files with GRCh38 positions or 7 for REVEL files with GRCh37 positions only .\n"; } $self->{revel_file_columns} = $column_count; my $assembly = $self->{config}->{assembly}; die "specify assembly using --assembly [assembly]\n" unless defined $assembly; my %assembly_to_hdr = ('GRCh37' => 'hg19_pos', 'GRCh38' => 'grch38_pos'); if (! grep {$_ eq $assembly_to_hdr{$assembly}} @{$self->{headers}}) { die "ERROR: Assembly is " . $assembly . " but REVEL file does not contain " . $assembly_to_hdr{$assembly} . " in header.\n"; } my ($start_key, $end_key) = ('start_grch38', 'end_grch38'); if ($assembly eq 'GRCh37') { ($start_key, $end_key) = ('start_grch37', 'end_grch37'); } $self->{revel_start_key} = $start_key; $self->{revel_end_key} = $end_key; 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 && $_->{$self->{revel_start_key}} == $vf->{start} && $_->{$self->{revel_end_key}} == $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 @values = split /\t/, $line; # the lastest version also contains GRCh38 coordinates if ($self->{revel_file_columns} == 8 || $self->{revel_file_columns} == 9) { my ($c, $s_grch37, $s_grch38, $ref, $alt, $refaa, $altaa, $revel_value, $transcript_id ) = @values; return { alt => $alt, start_grch37 => $s_grch37, end_grch37 => $s_grch37, start_grch38 => $s_grch38, end_grch38 => $s_grch38, altaa => $altaa, result => { REVEL => $revel_value, } }; } # the first version only has GRCh37 coordinates elsif ($self->{revel_file_columns} == 7) { my ($c, $s, $ref, $alt, $refaa, $altaa, $revel_value) = @values; return { alt => $alt, start_grch37 => $s, end_grch37 => $s, altaa => $altaa, result => { REVEL => $revel_value, } }; } else { return; } } sub get_start { return $_[1]->{start}; } sub get_end { return $_[1]->{end}; } 1;