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REVEL.pm
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REVEL.pm
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=head1 LICENSE
Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
Copyright [2016-2024] 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 --assembly GRCh37 --plugin REVEL,file=/path/to/revel/data.tsv.gz
./vep -i variations.vcf --assembly GRCh38 --plugin REVEL,file=/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
Running options:
If available, the plugin will match the scores by transcript id (default).
Using the flag '1' the plugin will not try to match by transcript id.
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 plugin can then be run as default:
./vep -i variations.vcf --assembly GRCh38 --plugin REVEL,file=/path/to/revel/data.tsv.gz
or with the option to not match by transcript id:
./vep -i variations.vcf --assembly GRCh38 --plugin REVEL,file=/path/to/revel/data.tsv.gz,no_match=1
Requirements:
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::Sequence qw(get_matched_variant_alleles);
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);
$self->get_user_params();
#$self->get_user_params();
my $params = $self->params_to_hash();
my @key_params;
my $file;
if (!%{$params}) {
$file = $self->params->[0];
$self->{no_match} = $self->params->[1] if ( defined ($self->params->[1] ) );
} else {
$file = $params->{file};
$self->{no_match} = $params->{no_match} if (defined ($params->{no_match}));
}
# get column count in REVEL file from header line
$self->add_file($file);
open HEAD, "tabix -fh $file 1:1-1 2>&1 | ";
while(<HEAD>) {
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";
}
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->base_variation_feature->alt_alleles;
my $tr_stable_id = $tva->transcript->stable_id;
my @data = @{$self->get_data($vf->{chr}, $vf->{start}, $vf->{end})};
foreach (@data) {
# Check the assembly to know which start to use
my $assembly = $self->{config}->{assembly};
my $revel_start = $assembly =~ /37/ ? $_->{start_grch37} : $_->{start_grch38};
my $matches = get_matched_variant_alleles(
{
ref => $vf->ref_allele_string,
alts => $allele,
pos => $vf->{start},
strand => $vf->strand
},
{
ref => $_->{ref},
alts => [$_->{alt}],
pos => $revel_start,
}
);
if (@$matches) {
if ($_->{transcript_ids} && !$self->{no_match}){
foreach my $tr_id (split /;/, $_->{transcript_ids}){
return $_->{result} if ($tr_id eq $tr_stable_id && $_->{altaa} eq $tva->peptide);
}
}
else {
return $_->{result} if ($_->{altaa} eq $tva->peptide);
}
}
}
return {};
}
sub parse_data {
my ($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 {
chr => $c,
ref => $ref,
alt => $alt,
start_grch37 => $s_grch37,
end_grch37 => $s_grch37,
start_grch38 => $s_grch38,
end_grch38 => $s_grch38,
altaa => $altaa,
transcript_ids => $transcript_id,
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 {
chr => $c,
ref => $ref,
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;