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=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;