From becd2dfc16629e22b6c232eaa6f931b03e3be63e Mon Sep 17 00:00:00 2001
From: Yuan Chen <yuan@sanger.ac.uk>
Date: Wed, 13 Jul 2005 14:42:39 +0000
Subject: [PATCH] added the way to calculate splice site change caused by
allele change
---
.../Bio/EnsEMBL/Utils/TranscriptAlleles.pm | 96 +++++++++++--------
1 file changed, 58 insertions(+), 38 deletions(-)
diff --git a/modules/Bio/EnsEMBL/Utils/TranscriptAlleles.pm b/modules/Bio/EnsEMBL/Utils/TranscriptAlleles.pm
index 01124daf45..2d2b925e68 100644
--- a/modules/Bio/EnsEMBL/Utils/TranscriptAlleles.pm
+++ b/modules/Bio/EnsEMBL/Utils/TranscriptAlleles.pm
@@ -44,7 +44,7 @@ use vars qw(@ISA @EXPORT_OK);
@ISA = qw(Exporter);
-@EXPORT_OK = qw(&get_all_ConsequenceType);
+@EXPORT_OK = qw(get_all_ConsequenceType type_variation);
use Data::Dumper;
@@ -176,26 +176,6 @@ sub type_variation {
throw("Not possible to calculate the consequence type for ",ref($var)," : Bio::EnsEMBL::Variation::ConsequenceType object expected");
}
- # ARNE: need the following:
- # $var and $tr need to have the same slice attached
- # if not, its difficult to compare the variations and the
- # transcript. If one or both are on a strain slice the
- # coordinate transformations DONT WORK CORRECTLY
-
- # if( $tr->slice() != $var->slice() ) {
-
-# # problem: Are the coordinates comparable?
-# # throw here, or warn and return, otherwise its too difficult
-# if( $tr->slice()->is_not_strainSlice() &&
-# $var->slice()->is_not_strainSlice() ) {
-# # coordintes are transferable
-# } else {
-# # coordinates are not transferable
-# }
-# } else {
-# # yes they are comparable
-# }
-
my $tm = $tr->get_TranscriptMapper();
my @coords = $tm->genomic2cdna($var->start,
$var->end,
@@ -219,6 +199,23 @@ sub type_variation {
return \@out;
}
+ my @coords_splice_2 = $tm->genomic2cdna($var->start -2, $var->end +2, $var->strand);
+ my @coords_splice_3 = $tm->genomic2cdna($var->start -3, $var->end +3, $var->strand);
+ my @coords_splice_8 = $tm->genomic2cdna($var->start -8, $var->end +8, $var->strand);
+
+ my ($splice_site_2, $splice_site_3, $splice_site_8);
+
+ if (scalar @coords_splice_2 >1) {
+ $splice_site_2=1;
+ }
+ elsif (scalar @coords_splice_3 >1) {
+ $splice_site_3=1;
+ }
+ elsif (scalar @coords_splice_8 >1) {
+ $splice_site_8=1;
+ }
+
+
my $c = $coords[0];
if($c->isa('Bio::EnsEMBL::Mapper::Gap')) {
@@ -235,7 +232,19 @@ sub type_variation {
# variation must be intronic since mapped to cdna gap, but is within
# transcript
- $var->type('INTRONIC');
+
+
+ if ($splice_site_2) {
+ $var->splice_site('ESSENTIAL_SPLICE_SITE');
+ $var->type('INTRONIC');
+ }
+ elsif ($splice_site_3 or $splice_site_8) {
+ $var->splice_site('SPLICE_SITE');
+ $var->type('INTRONIC');
+ }
+ else {
+ $var->type('INTRONIC');
+ }
return [$var];
}
@@ -272,7 +281,7 @@ sub type_variation {
}
return [$var];
}
-
+
$var->cds_start( $c->start() );
$var->cds_end( $c->end() );
@@ -283,18 +292,12 @@ sub type_variation {
throw("Unexpected: Could map to CDS but not to peptide coordinates.");
}
- my @coords_amp = $tm->genomic2pep($var->start -2, $var->end +2, $var->strand);
-
- if (@coords_amp != @coords){
- $var->type( 'SPLICE_SITE' );
- }
-
$c = $coords[0];
$var->aa_start( $c->start());
$var->aa_end( $c->end());
- apply_aa_change($tr, $var);
+ apply_aa_change($tr, $var, $splice_site_2, $splice_site_3);
return [$var];
}
@@ -306,6 +309,8 @@ sub type_variation {
sub apply_aa_change {
my $tr = shift;
my $var = shift;
+ my $splice_site_2 = shift;
+ my $splice_site_3 = shift;
#my $peptide = $tr->translate->seq();
#to consider stop codon as well
@@ -323,7 +328,7 @@ sub apply_aa_change {
my $peptide = $mrna_seqobj->translate(undef,undef,undef,$codon_table)->seq;
my $len = $var->aa_end - $var->aa_start + 1;
my $old_aa = substr($peptide, $var->aa_start -1 , $len);
- print "old aa $old_aa \n";
+
my $codon_cds_start = $var->aa_start * 3 - 2;
my $codon_cds_end = $var->aa_end * 3;
my $codon_len = $codon_cds_end - $codon_cds_start + 1;
@@ -343,8 +348,10 @@ sub apply_aa_change {
if(abs(length($a) - $var_len) % 3) {
# frameshifting variation, do not set peptide_allele string
# since too complicated and could be very long
- $var->type('FRAMESHIFT_CODING');
- return;
+
+ $var->type('FRAMESHIFT_CODING');
+
+ return [$var];
}
if($codon_len == 0) { # insertion
@@ -382,13 +389,26 @@ sub apply_aa_change {
}
if(@aa_alleles > 1) {
- if (! defined $var->type) {
- $var->type('NON_SYNONYMOUS_CODING');
+ if ( ! defined $var->type ){
+ if ($splice_site_2 or $splice_site_3) {
+ $var->splice_site('SPLICE_SITE');
+ $var->type('NON_SYNONYMOUS_CODING');
+ }
+ else {
+ $var->type('NON_SYNONYMOUS_CODING');
+ }
}
- } else {
- $var->type('SYNONYMOUS_CODING');
}
-
+ else {
+ if (($splice_site_2 or $splice_site_3) and $aa_alleles[0] !~ /\*/) {
+ $var->splice_site('SPLICE_SITE');
+ $var->type('SYNONYMOUS_CODING');
+ }
+ else {
+ $var->type('SYNONYMOUS_CODING');
+ }
+ }
+
$var->aa_alleles(\@aa_alleles);
}
--
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