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# BioPerl module for Bio::Variation::DNAMutation
#
# Please direct questions and support issues to <bioperl-l@bioperl.org>
#
# Cared for by Heikki Lehvaslaiho <heikki-at-bioperl-dot-org>
#
# Copyright Heikki Lehvaslaiho
#
# You may distribute this module under the same terms as perl itself
# POD documentation - main docs before the code
=head1 NAME
Bio::Variation::DNAMutation - DNA level mutation class
=head1 SYNOPSIS
$dnamut = Bio::Variation::DNAMutation->new
('-start' => $start,
'-end' => $end,
'-length' => $len,
'-upStreamSeq' => $upflank,
'-dnStreamSeq' => $dnflank,
'-proof' => $proof,
'-isMutation' => 1,
'-mut_number' => $mut_number
);
$a1 = Bio::Variation::Allele->new;
$a1->seq('a');
$dnamut->allele_ori($a1);
my $a2 = Bio::Variation::Allele->new;
$a2->seq('t');
$dnamut->add_Allele($a2);
print "Restriction changes are ", $dnamut->restriction_changes, "\n";
# add it to a SeqDiff container object
$seqdiff->add_Variant($dnamut);
=head1 DESCRIPTION
The instantiable class Bio::Variation::DNAMutation describes basic
sequence changes in genomic DNA level. It uses methods defined in
superclass Bio::Variation::VariantI. See L<Bio::Variation::VariantI>
for details.
If the variation described by a DNAMutation object is transcibed, link
the corresponding Bio::Variation::RNAChange object to it using
method RNAChange(). See L<Bio::Variation::RNAChange> for more information.
=head1 FEEDBACK
=head2 Mailing Lists
User feedback is an integral part of the evolution of this and other
Bioperl modules. Send your comments and suggestions preferably to the
Bioperl mailing lists Your participation is much appreciated.
bioperl-l@bioperl.org - General discussion
http://bioperl.org/wiki/Mailing_lists - About the mailing lists
=head2 Support
Please direct usage questions or support issues to the mailing list:
I<bioperl-l@bioperl.org>
rather than to the module maintainer directly. Many experienced and
reponsive experts will be able look at the problem and quickly
address it. Please include a thorough description of the problem
with code and data examples if at all possible.
=head2 Reporting Bugs
Report bugs to the Bioperl bug tracking system to help us keep track
the bugs and their resolution. Bug reports can be submitted via the
web:
https://github.com/bioperl/bioperl-live/issues
=head1 AUTHOR - Heikki Lehvaslaiho
Email: heikki-at-bioperl-dot-org
=head1 APPENDIX
The rest of the documentation details each of the object
methods. Internal methods are usually preceded with a _
=cut
# Let the code begin...
package Bio::Variation::DNAMutation;
use strict;
# Object preamble - inheritance
use base qw(Bio::Variation::VariantI);
sub new {
my($class,@args) = @_;
my $self = $class->SUPER::new(@args);
my ($start, $end, $length, $strand, $primary, $source,
$frame, $score, $gff_string,
$allele_ori, $allele_mut, $upstreamseq, $dnstreamseq,
$label, $status, $proof, $region, $region_value, $region_dist, $numbering,
$cpg, $mut_number, $ismutation) =
$self->_rearrange([qw(START
END
LENGTH
STRAND
PRIMARY
SOURCE
FRAME
SCORE
GFF_STRING
ALLELE_ORI
ALLELE_MUT
UPSTREAMSEQ
DNSTREAMSEQ
LABEL
STATUS
PROOF
REGION
REGION_VALUE
REGION_DIST
NUMBERING
CPG
MUT_NUMBER
ISMUTATION
)],
@args);
$self->primary_tag("Variation");
$self->{ 'alleles' } = [];
$start && $self->start($start);
$end && $self->end($end);
$length && $self->length($length);
$strand && $self->strand($strand);
$primary && $self->primary_tag($primary);
$source && $self->source_tag($source);
$frame && $self->frame($frame);
$score && $self->score($score);
$gff_string && $self->_from_gff_string($gff_string);
$allele_ori && $self->allele_ori($allele_ori);
$allele_mut && $self->allele_mut($allele_mut);
$upstreamseq && $self->upStreamSeq($upstreamseq);
$dnstreamseq && $self->dnStreamSeq($dnstreamseq);
$label && $self->label($label);
$status && $self->status($status);
$proof && $self->proof($proof);
$region && $self->region($region);
$region_value && $self->region_value($region_value);
$region_dist && $self->region_dist($region_dist);
$numbering && $self->numbering($numbering);
$mut_number && $self->mut_number($mut_number);
$ismutation && $self->isMutation($ismutation);
$cpg && $self->CpG($cpg);
return $self; # success - we hope!
}
=head2 CpG
Title : CpG
Usage : $obj->CpG()
Function: sets and returns boolean values for variation
hitting a CpG site. Unset value return -1.
Example : $obj->CpG()
Returns : boolean
Args : optional true of false value
=cut
sub CpG {
my ($obj,$value) = @_;
if( defined $value) {
$value ? ($value = 1) : ($value = 0);
$obj->{'cpg'} = $value;
}
elsif (not defined $obj->{'label'}) {
$obj->{'cpg'} = $obj->_CpG_value;
}
else {
return $obj->{'cpg'};
}
}
sub _CpG_value {
my ($self) = @_;
if ($self->allele_ori eq $self->allele_mut and length ($self->allele_ori) == 1 ) {
# valid only for point mutations
# CpG methylation-mediated deamination:
# CG -> TG | CG -> CA substitutions
# implementation here is less strict: if CpG dinucleotide was hit
if ( ( ($self->allele_ori eq 'c') && (substr($self->upStreamSeq, 0, 1) eq 'g') ) ||
( ($self->allele_ori eq 'g') && (substr($self->dnStreamSeq, -1, 1) eq 'c') ) ) {
return 1;
}
else {
return 0;
}
} else {
$self->warn('CpG makes sense only in the context of point mutation');
return;
}
}
=head2 RNAChange
Title : RNAChange
Usage : $mutobj = $obj->RNAChange;
: $mutobj = $obj->RNAChange($objref);
Function: Returns or sets the link-reference to a mutation/change object.
If there is no link, it will return undef
Returns : an obj_ref or undef
=cut
sub RNAChange {
my ($self,$value) = @_;
if (defined $value) {
if( ! $value->isa('Bio::Variation::RNAChange') ) {
$self->throw("Is not a Bio::Variation::RNAChange object but a [$self]");
return;
}
else {
$self->{'RNAChange'} = $value;
}
}
unless (exists $self->{'RNAChange'}) {
return;
} else {
return $self->{'RNAChange'};
}
}
=head2 label
Title : label
Usage : $obj->label();
Function:
Sets and returns mutation event label(s). If value is not
set, or no argument is given returns false. Each
instantiable subclass of L<Bio::Variation::VariantI> needs
to implement this method. Valid values are listed in
'Mutation event controlled vocabulary' in
http://www.ebi.ac.uk/mutations/recommendations/mutevent.html.
Example :
Returns : string
Args : string
=cut
sub label {
my ($self, $value) = @_;
my ($o, $m, $type);
$o = $self->allele_ori->seq if $self->allele_ori and $self->allele_ori->seq;
$m = $self->allele_mut->seq if $self->allele_mut and $self->allele_mut->seq;
if (not $o and not $m ) {
$self->warn("[DNAMutation, label] Both alleles should not be empty!\n");
$type = 'no change'; # is this enough?
}
elsif ($o && $m && length($o) == length($m) && length($o) == 1) {
$type = 'point';
$type .= ", ". _point_type_label($o, $m);
}
elsif (not $o ) {
$type = 'insertion';
}
elsif (not $m ) {
$type = 'deletion';
}
else {
$type = 'complex';
}
$self->{'label'} = $type;
return $self->{'label'};
}
sub _point_type_label {
my ($o, $m) = @_;
my ($type);
my %transition = ('a' => 'g',
'g' => 'a',
'c' => 't',
't' => 'c');
$o = lc $o;
$m = lc $m;
if ($o eq $m) {
$type = 'no change';
}
elsif ($transition{$o} eq $m ) {
$type = 'transition';
}
else {
$type = 'transversion';
}
}
=head2 sysname
Title : sysname
Usage : $self->sysname
Function:
This subroutine creates a string corresponding to the
'systematic name' of the mutation. Systematic name is
specified in Antonorakis & MDI Nomenclature Working Group:
Human Mutation 11:1-3, 1998.
Returns : string
=cut
sub sysname {
my ($self,$value) = @_;
if( defined $value) {
$self->{'sysname'} = $value;
} else {
$self->warn('Mutation start position is not defined')
if not defined $self->start;
my $sysname = '';
# show the alphabet only if $self->SeqDiff->alphabet is set;
my $mol = '';
if ($self->SeqDiff ) {
if ($self->SeqDiff && $self->SeqDiff->alphabet && $self->SeqDiff->alphabet eq 'dna') {
$mol = 'g.';
}
elsif ($self->SeqDiff->alphabet && $self->SeqDiff->alphabet eq 'rna') {
$mol = 'c.';
}
}
my $sep;
if ($self->isMutation) {
$sep = '>';
} else {
$sep = '|';
}
my $sign = '+';
$sign = '' if $self->start < 1;
$sysname .= $mol ;#if $mol;
$sysname .= $sign. $self->start;
my @alleles = $self->each_Allele;
$self->allele_mut($alleles[0]);
$sysname .= 'del' if $self->label =~ /deletion/;
$sysname .= 'ins' if $self->label =~ /insertion/;
$sysname .= uc $self->allele_ori->seq if $self->allele_ori->seq;
#push @alleles, $self->allele_mut if $self->allele_mut;
foreach my $allele (@alleles) {
$self->allele_mut($allele);
$sysname .= $sep if $self->label =~ /point/ or $self->label =~ /complex/;
$sysname .= uc $self->allele_mut->seq if $self->allele_mut->seq;
}
$self->{'sysname'} = $sysname;
#$self->{'sysname'} = $sign. $self->start.
# uc $self->allele_ori->seq. $sep. uc $self->allele_mut->seq;
}
return $self->{'sysname'};
}
1;
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