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Remove POSIX ceil dep from Downstream #371

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Sep 6, 2021
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120 changes: 65 additions & 55 deletions Downstream.pm
Original file line number Diff line number Diff line change
Expand Up @@ -55,12 +55,23 @@ use strict;
use warnings;

use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
use POSIX qw(ceil);

use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);

sub new {
my $class = shift;

my $self = $class->SUPER::new(@_);

if($self->{config}{offline} && !$self->{config}{fasta}) {
die("ERROR: cannot function in offline mode without a FASTA file\n");
}

return $self;
}

sub version {
return '2.3';
return '2.4';
}

sub feature_types {
Expand All @@ -80,61 +91,60 @@ sub get_header_info {

sub run {
my ($self, $tva) = @_;

my @ocs = @{$tva->get_all_OverlapConsequences};

if(grep {$_->SO_term eq 'frameshift_variant'} @ocs) {

# can't do it for splice sites
return {} if grep {$_->SO_term =~ /splice/} @ocs;

my $tv = $tva->transcript_variation;
my $tr = $tv->transcript;
my $cds_seq = defined($tr->{_variation_effect_feature_cache}) ? $tr->{_variation_effect_feature_cache}->{translateable_seq} : $tr->translateable_seq;

# get the sequence to translate
my ($low_pos, $high_pos) = sort {$a <=> $b} ($tv->cds_start, $tv->cds_end);
my $is_insertion = $tv->cds_start > $tv->cds_end ? 1 : 0;
my $last_complete_codon = (ceil($low_pos / 3) - 1) * 3;
my $before_var_seq = substr $cds_seq, $last_complete_codon, $low_pos - $last_complete_codon - ($is_insertion ? 0 : 1);
my $after_var_seq = substr $cds_seq, $high_pos - ($is_insertion ? 1 : 0);
my $to_translate = $before_var_seq.$tva->feature_seq.$after_var_seq;
my $three_prime_utr_seq = $tr->three_prime_utr->seq() if ($tr->three_prime_utr);
$to_translate = $to_translate.$three_prime_utr_seq if ($three_prime_utr_seq);
$to_translate =~ s/\-//g;

# create a bioperl object
my $codon_seq = Bio::Seq->new(
-seq => $to_translate,
-moltype => 'dna',
-alphabet => 'dna'
);

# get codon table
my $codon_table;
if(defined($tr->{_variation_effect_feature_cache})) {
$codon_table = $tr->{_variation_effect_feature_cache}->{codon_table} || 1;
}
else {
my ($attrib) = @{$tr->slice->get_all_Attributes('codon_table')};
$codon_table = $attrib ? $attrib->value || 1 : 1;
}

# translate
my $new_pep = $codon_seq->translate(undef, undef, undef, $codon_table)->seq();
$new_pep =~ s/\*.*//;

# compare lengths
my $translation = defined($tr->{_variation_effect_feature_cache}) && defined($tr->{_variation_effect_feature_cache}->{peptide}) ? $tr->{_variation_effect_feature_cache}->{peptide} : $tr->translation->seq;
my $new_length = ($tv->translation_start < $tv->translation_end ? $tv->translation_start : $tv->translation_end) + length($new_pep);

return {
DownstreamProtein => $new_pep,
ProteinLengthChange => $new_length - length($translation),
};

my @SO_terms = map { $_->SO_term } @{$tva->get_all_OverlapConsequences};

return {} unless grep { $_ eq 'frameshift_variant' } @SO_terms;

return {} if grep { /splice/ } @SO_terms;

my $tv = $tva->transcript_variation;
my $tr = $tv->transcript;

my $cds_seq = defined($tr->{_variation_effect_feature_cache})
? $tr->{_variation_effect_feature_cache}->{translateable_seq}
: $tr->translateable_seq;

my ($start, $end) = ($tv->cds_start, $tv->cds_end);

substr($cds_seq, $start - 1, $end - $start + 1) = $tva->seq_length > 0 ? $tva->feature_seq : '';

my $low_pos = $start > $end ? $end : $start;
my $last_complete_codon = $low_pos - ( ( ( $low_pos - 1 ) % 3 ) + 1 );

my $downstream_seq = substr($cds_seq, $last_complete_codon > 0 ? $last_complete_codon : 0);
my $three_prime_utr = $tr->three_prime_utr ? $tr->three_prime_utr->seq() : '';

my $codon_seq = Bio::Seq->new(
-seq => $downstream_seq . $three_prime_utr,
-moltype => 'dna',
-alphabet => 'dna'
);

my $codon_table;
if(defined($tr->{_variation_effect_feature_cache})) {
$codon_table = $tr->{_variation_effect_feature_cache}->{codon_table} || 1;
}
else {
my ($attrib) = @{$tr->slice->get_all_Attributes('codon_table')};
$codon_table = $attrib ? $attrib->value || 1 : 1;
}

return {};
my $new_pep = $codon_seq->translate(undef, undef, undef, $codon_table)->seq();
$new_pep =~ s/\*.*//;

my $translation = defined($tr->{_variation_effect_feature_cache}->{peptide})
? $tr->{_variation_effect_feature_cache}->{peptide}
: $tr->translation->seq;

my ($pep_start, $pep_end) = ($tv->translation_start, $tv->translation_end);

my $new_length = ($pep_start < $pep_end ? $pep_start : $pep_end) + length($new_pep);

return {
DownstreamProtein => $new_pep,
ProteinLengthChange => $new_length - length($translation),
};
}

1;
Expand Down