Raw content of Deletion
<![CDATA[use strict;
use warnings;
package Deletion;
use InterimExon;
use StatMsg;
use Length;
use Utils qw(print_exon);
use Bio::EnsEMBL::Utils::Exception qw(throw info);
###############################################################################
# process_delete
#
# processes a deletion in an exon
###############################################################################
sub process_delete {
my $cdna_del_pos_ref = shift;
my $del_len = shift;
my $exon = shift;
my $transcript = shift;
my $entire_delete = shift;
my $del_start = $$cdna_del_pos_ref + 1;
my $del_end = $del_start + $del_len - 1;
info((($entire_delete) ? 'entire ' : '')."delete ($del_len) at " .
$$cdna_del_pos_ref);
info("BEFORE cds: ". $transcript->cdna_coding_start().'-'.
$transcript->cdna_coding_end());
info("BEFORE del_start = $del_start");
# sanity check, deletion should be completely in
# or adjacent to exon boundaries
if(!$entire_delete && ($del_start < $exon->cdna_start() - 1 ||
$del_start > $exon->cdna_end() + 1)) {
throw("Unexpected: deletion is outside of exon boundary\n" .
" del_start = $del_start\n" .
" cdna_exon_start =". $exon->cdna_start() .
" cdna_exon_end =". $exon->cdna_end());
}
# break delete into composite parts and deal with each part seperately
#
# deal with five prime UTR portion of delete
#
if($del_start < $transcript->cdna_coding_start()) {
my $utr_del_len;
if($del_end >= $transcript->cdna_coding_start()) {
$utr_del_len = $transcript->cdna_coding_start() - $del_start;
} else {
$utr_del_len = $del_len;
}
process_five_prime_utr_delete($cdna_del_pos_ref, $utr_del_len,
$exon, $transcript);
# take away the processed part of the deletion
$del_start = $$cdna_del_pos_ref + 1;
$del_len -= $utr_del_len;
$del_end = $del_start + $del_len - 1;
}
if($del_len == 0) {
# no deletion left
$exon->fix_phase($transcript) if(!$entire_delete);
return;
}
#
# deal with CDS portion of delete
#
if($del_end >= $transcript->cdna_coding_start() &&
$del_start <= $transcript->cdna_coding_end()) {
my $cds_del_len;
if($del_end > $transcript->cdna_coding_end()) {
$cds_del_len = $transcript->cdna_coding_end() - $del_start + 1;
} else {
$cds_del_len = $del_len;
}
process_cds_delete($cdna_del_pos_ref, $cds_del_len, $exon, $transcript,
$entire_delete);
# take away the processed part of the deletion
# the cdna start is in the same place because
$del_start += $$cdna_del_pos_ref + 1;
$del_len -= $cds_del_len;
$del_end = $del_start + $del_len - 1;
}
if($del_len == 0) {
# no deletion left
$exon->fix_phase($transcript) if(!$entire_delete);;
return;
}
#
# deal with 3prime portion of delete
#
# sanity check:
if($del_start <= $transcript->cdna_coding_end()) {
throw("Unexpected. 3' UTR delete starts before coding end.");
}
process_three_prime_utr_delete($cdna_del_pos_ref, $del_len, $exon,
$transcript);
$exon->fix_phase($transcript) if(!$entire_delete);
return;
}
###############################################################################
# process_five_prime_utr_delete
#
# processes a deletion in the five prime utr of a transcript
###############################################################################
sub process_five_prime_utr_delete {
my $cdna_del_pos_ref = shift;
my $del_len = shift;
my $exon = shift;
my $transcript = shift;
info("delete ($del_len) in 5' utr");
# shift up the CDS
$transcript->move_cdna_coding_start(-$del_len);
$transcript->move_cdna_coding_end(-$del_len);
# create a status message and add it to the exon
my $code = StatMsg::EXON | StatMsg::DELETE | StatMsg::FIVE_PRIME |
StatMsg::UTR | Length::length2code($del_len);
$exon->add_StatMsg(StatMsg->new($code));
return;
}
###############################################################################
# process_three_prime_utr_delete
#
# processes a deletion in the three prime utr of a transcript
###############################################################################
sub process_three_prime_utr_delete {
my $cdna_del_pos_ref = shift;
my $del_len = shift;
my $exon = shift;
my $transcript = shift;
#do not have to do anything...
info("delete ($del_len) in 3' utr");
# create a status message and add it to the exon
my $code = StatMsg::EXON | StatMsg::DELETE | StatMsg::THREE_PRIME |
StatMsg::UTR | Length::length2code($del_len);
$exon->add_StatMsg(StatMsg->new($code));
return;
}
###############################################################################
# process_cds_delete
#
# processes a deletion in the cds of a transcript
###############################################################################
sub process_cds_delete {
my $cdna_del_pos_ref = shift;
my $del_len = shift;
my $exon = shift;
my $transcript = shift;
my $entire_delete = shift;
info("delete ($del_len) in cds");
my $del_start = $$cdna_del_pos_ref + 1;
my $del_end = $del_start + $del_len - 1;
my $code = StatMsg::EXON | StatMsg::DELETE | StatMsg::CDS |
Length::length2code($del_len);
my $frameshift = $del_len % 3;
#
# case 1: delete is all of CDS
#
if($del_start == $transcript->cdna_coding_start() &&
$del_end == $transcript->cdna_coding_end()) {
info("delete ($del_len) is all of cds");
$code |= StatMsg::ENTIRE;
# move up CDS end to account for CDS deletion
$transcript->move_cdna_coding_end(-$del_len);
}
#
# case 2: delete is at start of CDS
#
elsif($del_start == $transcript->cdna_coding_start()) {
info("delete ($del_len) at start of cds");
$code |= StatMsg::FIVE_PRIME;
# move up CDS end to account for CDS deletion
$transcript->move_cdna_coding_end(-$del_len);
if($frameshift) {
$code |= StatMsg::FRAMESHIFT if($frameshift);
# move down CDS start to put reading frame back (shrink CDS)
info("shifting cds start to restore reading frame");
$transcript->move_cdna_coding_start(3 - $frameshift);
}
}
#
# case 3: delete is at end of CDS
#
elsif($del_end == $transcript->cdna_coding_end()) {
info("delete ($del_len) at end of cds");
$code |= StatMsg::THREE_PRIME;
# move up CDS end to account for CDS deletion
$transcript->move_cdna_coding_end(-$del_len);
if($frameshift) {
$code |= StatMsg::FRAMESHIFT if($frameshift);
# move up CDS end to put reading frame back (shrink CDS)
info("shifting cds end to restore reading frame");
$transcript->move_cdna_coding_end($frameshift-3);
}
}
#
# case 4: delete is in middle of CDS
#
elsif($del_end > $transcript->cdna_coding_start() &&
$del_start < $transcript->cdna_coding_end()) {
info("delete ($del_len) in middle of cds");
$code |= StatMsg::MIDDLE;
# move up CDS end to account for CDS deletion
$transcript->move_cdna_coding_end(-$del_len);
if($frameshift && !$entire_delete) {
info("BEFORE CDS DELETE:");
print_exon($exon, $transcript);
$code |= StatMsg::FRAMESHIFT if($frameshift);
# this is going to require splitting the exon
# to make a frameshift deletion
#first exon is going to end right before deletion
my $first_len = $del_start - $exon->cdna_start();
my $intron_len = 3 - $frameshift;
#reduce the length of the CDS by the length of the new intron
$transcript->move_cdna_coding_end(-$intron_len);
# the next match that is added to the cdna position will have too much
# sequence because we used part of the sequence to create the frameshift
# intron, compensate by reducing cdna position by intron len
$$cdna_del_pos_ref -= $intron_len;
info("introducing frameshift intron ($intron_len) " .
"to maintain reading frame");
# very short exons can be entirely consumed by the intron
if($intron_len == $exon->length()) {
# still adjust this 0 length intron, because its length
# is used in transcript splitting calculations
$exon->cdna_end($exon->cdna_end - $intron_len);
if($exon->strand() == 1) {
$exon->end($exon->end - $intron_len);
} else {
$exon->start($exon->start + $intron_len);
}
$code |= StatMsg::ALL_INTRON;
$exon->fail(1);
}
elsif($intron_len > $exon->length()) {
$code |= StatMsg::CONFUSED | StatMsg::ALL_INTRON;
# still adjust this negative length exon b/c its length is used
# in transcript splitting calculations
$exon->cdna_end($exon->cdna_end - $intron_len);
if($exon->strand() == 1) {
$exon->end($exon->end - $intron_len);
} else {
$exon->start($exon->start + $intron_len);
}
$exon->fail(1);
}
elsif($first_len + $intron_len >= $exon->length()) {
# we may have encountered a delete at the very end of the exon
# in this case we have to take the intron out of the end of this exon
# since we are not creating a second one
if($exon->strand() == 1) {
$exon->end($exon->end - $intron_len);
} else {
$exon->start($exon->start + $intron_len);
}
$exon->cdna_end($exon->cdna_end - $intron_len);
} else {
# second exon is going to start right after 'frameshift intron'
if($exon->strand == 1) {
# end the current exon at the beginning of the deletion
# watch out though, because we may be at the very beginning of
# the exon in which case we do not want to create one
if($first_len) {
my $first_exon = InterimExon->new();
# Copy the original exon and adjust the coords as necessary
# Note that these exons will share stat msgs which is what
# we want.
%{$first_exon} = %{$exon};
$first_exon->cdna_end($exon->cdna_start() + $first_len - 1);
$first_exon->end($first_exon->start() + $first_len - 1);
$transcript->add_Exon($first_exon);
info("FIRST EXON:");
info($first_exon, $transcript);
$exon->add_StatMsg(StatMsg->new(StatMsg::EXON | StatMsg::SPLIT));
$exon->cdna_start($first_exon->cdna_end() + 1);
$first_exon->set_split_phases($exon, $transcript);
}
# start next exon after new intron
$exon->start($exon->start() + $first_len + $intron_len);
$exon->cdna_end($exon->cdna_end - $intron_len);
} else {
if($first_len) {
my $first_exon = InterimExon->new();
# copy the original exon and adjust the coords as necessary
# these exons will share stat msgs
%{$first_exon} = %{$exon};
$first_exon->cdna_end($exon->cdna_start + $first_len - 1);
$first_exon->start($exon->end() - $first_len + 1);
$transcript->add_Exon($first_exon);
info("FIRST EXON:");
print_exon($first_exon, $transcript);
$exon->add_StatMsg(StatMsg->new(StatMsg::EXON | StatMsg::SPLIT));
$exon->cdna_start($first_exon->cdna_end() + 1);
$first_exon->set_split_phases($exon, $transcript);
}
# start next exon after new intron
$exon->end($exon->end() - ($first_len + $intron_len));
$exon->cdna_end($exon->cdna_end - $intron_len);
}
}
info("AFTER CDS DELETE:");
print_exon($exon, $transcript);
}
}
# sanity check:
else {
throw("Unexpected: CDS delete appears to be outside of CDS:\n" .
" del_start = $del_start\n".
" del_end = $del_end\n" .
" cdna_coding_start = ".$transcript->cdna_coding_start() . "\n".
" cdna_coding_end = ".$transcript->cdna_coding_end() . "\n");
}
$exon->add_StatMsg(StatMsg->new($code));
return;
}
1;
]]>