Raw content of Bio::Variation::RNAChange
# $Id: RNAChange.pm,v 1.10 2002/10/22 07:38:49 lapp Exp $
#
# BioPerl module for Bio::Variation::RNAChange
#
# Cared for by Heikki Lehvaslaiho
#
# 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::RNAChange - Sequence change class for RNA level
=head1 SYNOPSIS
$rnachange = Bio::Variation::RNAChange->new
('-start' => $start,
'-end' => $end,
'-length' => $len,
'-codon_pos' => $cp,
'-upStreamSeq' => $upflank,
'-dnStreamSeq' => $dnflank,
'-proof' => $proof,
'-isMutation' => 1,
'-mut_number' => $mut_number
);
$a1 = Bio::Variation::Allele->new;
$a1->seq('a');
$rnachange->allele_ori($a1);
my $a2 = Bio::Variation::Allele->new;
$a2->seq('t');
$rnachange->add_Allele($a2);
$rnachange->allele_mut($a2);
print "The codon change is ", $rnachange->codon_ori,
">", $rnachange->codon_mut, "\n";
# add it to a SeqDiff container object
$seqdiff->add_Variant($rnachange);
# and create links to and from DNA level mutation objects
$rnachange->DNAMutation($dnamut);
$dnamut->RNAChange($rnachange);
=head1 DESCRIPTION
The instantiable class Bio::Variation::DNAMutation describes basic
sequence changes at RNA molecule level. It uses methods defined in
superclass Bio::Variation::VariantI. See L
for details.
You are normally expected to create a corresponding
Bio::Variation::DNAMutation object even if mutation is defined at
RNA level. The numbering follows then cDNA numbering. Link the
DNAMutation object to the RNAChange object using the method
DNAMutation(). If the variation described by a RNAChange object is
translated, link the corresponding Bio::Variation::AAChange object
to it using method AAChange(). See L and
L 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://bio.perl.org/MailList.html - About the mailing lists
=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
email or the web:
bioperl-bugs@bio.perl.org
http://bugzilla.bioperl.org/
=head1 AUTHOR - Heikki Lehvaslaiho
Email: heikki@ebi.ac.uk
Address:
EMBL Outstation, European Bioinformatics Institute
Wellcome Trust Genome Campus, Hinxton
Cambs. CB10 1SD, United Kingdom
=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::RNAChange;
use vars qw(@ISA);
use strict;
# Object preamble - inheritance
my $VERSION=1.0;
use Bio::Variation::VariantI;
use Bio::Tools::CodonTable;
@ISA = qw( Bio::Variation::VariantI );
sub new {
my($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,
$mut_number, $isMutation,
$codon_ori, $codon_mut, $codon_pos, $codon_table, $cds_end) =
$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
MUT_NUMBER
ISMUTATION
CODON_ORI
CODON_MUT
CODON_POS
TRANSLATION_TABLE
CDS_END
)],@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);
$codon_ori && $self->codon_ori($codon_ori);
$codon_mut && $self->codon_mut($codon_mut);
$codon_pos && $self->codon_pos($codon_pos);
$codon_table && $self->codon_table($codon_table);
$cds_end && $self->cds_end($cds_end);
return $self; # success - we hope!
}
=head2 codon_ori
Title : codon_ori
Usage : $obj->codon_ori();
Function:
Sets and returns codon_ori triplet. If value is not set,
creates the codon triplet from the codon position and
flanking sequences. The string has to be three characters
long. The character content is not checked.
Example :
Returns : string
Args : string
=cut
sub codon_ori {
my ($self,$value) = @_;
if (defined $value) {
if (length $value != 3) {
$self->warn("Codon string \"$value\" is not three characters long");
}
$self->{'codon_ori'} = $value;
}
elsif (! $self->{'codon_ori'}) {
my $codon_ori = '';
if ($self->region eq 'coding' && $self->start && $self->start >= 1) {
$self->warn('Codon position is not defined')
if not defined $self->codon_pos;
$self->warn('Upstream flanking sequence is not defined')
if not defined $self->upStreamSeq;
$self->warn('Downstream flanking sequence is not defined')
if not defined $self->dnStreamSeq;
my $cpos = $self->codon_pos;
$codon_ori = substr($self->upStreamSeq, -$cpos +1 , $cpos-1);
$codon_ori .= substr($self->allele_ori->seq, 0, 4-$cpos)
if $self->allele_ori and $self->allele_ori->seq;
$codon_ori .= substr($self->dnStreamSeq, 0, 3-length($codon_ori));
}
$self->{'codon_ori'} = lc $codon_ori;
}
return $self->{'codon_ori'};
}
=head2 codon_mut
Title : codon_mut
Usage : $obj->codon_mut();
Function:
Sets and returns codon_mut triplet. If value is not
set, creates the codon triplet from the codon position and
flanking sequences. Return undef for other than point mutations.
Example :
Returns : string
Args : string
=cut
sub codon_mut {
my ($self,$value) = @_;
if (defined $value) {
if (length $value != 3 ) {
$self->warn("Codon string \"$value\" is not three characters long");
}
$self->{'codon_mut'} = $value;
}
else {
my $codon_mut = '';
if ($self->allele_ori->seq and $self->allele_mut->seq and
CORE::length($self->allele_ori->seq) == 1 and
CORE::length($self->allele_mut->seq) == 1 and
$self->region eq 'coding' and $self->start >= 1) {
$self->warn('Codon position is not defined')
if not defined $self->codon_pos;
$self->warn('Upstream flanking sequnce is not defined')
if not defined $self->upStreamSeq;
$self->warn('Downstream flanking sequnce is not defined')
if not defined $self->dnStreamSeq;
$self->throw('Mutated allele is not defined')
if not defined $self->allele_mut;
my $cpos = $self->codon_pos;
$codon_mut = substr($self->upStreamSeq, -$cpos +1 , $cpos-1);
$codon_mut .= substr($self->allele_mut->seq, 0, 4-$cpos)
if $self->allele_mut and $self->allele_mut->seq;
$codon_mut .= substr($self->dnStreamSeq, 0, 3-length($codon_mut));
$self->{'codon_mut'} = lc $codon_mut;
}
}
return $self->{'codon_mut'};
}
=head2 codon_pos
Title : codon_pos
Usage : $obj->codon_pos();
Function:
Sets and returns the position of the mutation start in the
codon. If value is not set, returns false.
Example :
Returns : 1,2,3
Args : none if get, the new value if set
=cut
sub codon_pos {
my ($self,$value) = @_;
if( defined $value) {
if ( $value !~ /[123]/ ) {
$self->throw("'$value' is not a valid codon position");
}
$self->{'codon_pos'} = $value;
}
return $self->{'codon_pos'};
}
=head2 codon_table
Title : codon_table
Usage : $obj->codon_table();
Function:
Sets and returns the codon table id of the RNA
If value is not set, returns 1, 'universal' code, as the default.
Example :
Returns : integer
Args : none if get, the new value if set
=cut
sub codon_table {
my ($self,$value) = @_;
if( defined $value) {
if ( not $value =~ /^\d$/ ) {
$self->throw("'$value' is not a valid codon table ID\n".
"Has to be a positive integer. Defaulting to 1\n");
} else {
$self->{'codon_table'} = $value;
}
}
if( ! exists $self->{'codon_table'} ) {
return 1;
} else {
return $self->{'codon_table'};
}
}
=head2 DNAMutation
Title : DNAMutation
Usage : $mutobj = $obj->DNAMutation;
: $mutobj = $obj->DNAMutation($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 DNAMutation {
my ($self,$value) = @_;
if (defined $value) {
if( ! $value->isa('Bio::Variation::DNAMutation') ) {
$self->throw("Is not a Bio::Variation::DNAMutation object but a [$self]");
return (undef);
}
else {
$self->{'DNAMutation'} = $value;
}
}
unless (exists $self->{'DNAMutation'}) {
return (undef);
} else {
return $self->{'DNAMutation'};
}
}
=head2 AAChange
Title : AAChange
Usage : $mutobj = $obj->AAChange;
: $mutobj = $obj->AAChange($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 AAChange {
my ($self,$value) = @_;
if (defined $value) {
if( ! $value->isa('Bio::Variation::AAChange') ) {
$self->throw("Is not a Bio::Variation::AAChange object but a [$self]");
return (undef);
}
else {
$self->{'AAChange'} = $value;
}
}
unless (exists $self->{'AAChange'}) {
return (undef);
} else {
return $self->{'AAChange'};
}
}
=head2 exons_modified
Title : exons_modified
Usage : $modified = $obj->exons_modified;
: $modified = $obj->exons_modified(1);
Function: Returns or sets information (example: a simple boolean flag) about
the modification of exons as a result of a mutation.
=cut
sub exons_modified {
my ($self,$value)=@_;
if (defined($value)) {
$self->{'exons_modified'}=$value;
}
return ($self->{'exons_modified'});
}
=head2 region
Title : region
Usage : $obj->region();
Function:
Sets and returns the name of the sequence region type or
protein domain at this location. If value is not set,
returns false.
Example :
Returns : string
Args : string
=cut
sub region {
my ($self,$value) = @_;
if( defined $value) {
$self->{'region'} = $value;
}
elsif (not defined $self->{'region'}) {
$self->warn('Mutation start position is not defined')
if not defined $self->start and $self->verbose;
$self->warn('Mutation end position is not defined')
if not defined $self->end and $self->verbose;
$self->warn('Length of the CDS is not defined, the mutation can be beyond coding region!')
if not defined $self->cds_end and $self->verbose;
$self->region('coding');
if ($self->end && $self->end < 0 ){
$self->region('5\'UTR');
}
elsif ($self->start && $self->cds_end && $self->start > $self->cds_end ) {
$self->region('3\'UTR');
}
}
return $self->{'region'};
}
=head2 cds_end
Title : cds_end
Usage : $cds_end = $obj->get_cds_end();
Function:
Sets or returns the cds_end from the beginning of the DNA sequence
to the coordinate start used to describe variants.
Should be the location of the last nucleotide of the
terminator codon of the gene.
Example :
Returns : value of cds_end, a scalar
Args :
=cut
sub cds_end {
my ($self, $value) = @_;
if (defined $value) {
$self->warn("[$value] is not a good value for sequence position")
if not $value =~ /^\d+$/ ;
$self->{'cds_end'} = $value;
} else {
$self->{'cds_end'} = $self->SeqDiff->cds_end if $self->SeqDiff;
}
return $self->{'cds_end'};
}
=head2 label
Title : label
Usage : $obj->label();
Function:
Sets and returns mutation event label(s). If value is not
set, or no argument is given returns false. Each
instantiable subclass of L needs
to implement this method. Valid values are listed in
'Mutation event controlled vocabulary' in
http://www.ebi.ac.uk/mutations/recommendations/mutevent.html.
Example :
Returns : string
Args : string
=cut
sub label {
my ($self) = @_;
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;
my $ct = Bio::Tools::CodonTable -> new ( -id => $self->codon_table );
if ($o and $m and CORE::length($o) == 1 and CORE::length($m) == 1) {
if (defined $self->AAChange) {
if ($self->start > 0 and $self->start < 4 ) {
$type = 'initiation codon';
}
elsif ($self->codon_ori && $ct->is_ter_codon($self->codon_ori) ) {
#AAChange->allele_ori and $self->AAChange->allele_ori->seq eq '*' ) {
$type = 'termination codon';
}
elsif ($self->codon_mut && $ct->is_ter_codon($self->codon_mut) ) {
#elsif ($self->AAChange->allele_mut and $self->AAChange->allele_mut->seq eq "*") {
$type = 'nonsense';
}
elsif ($o and $m and ($o eq $m or
$self->AAChange->allele_ori->seq eq
$self->AAChange->allele_mut->seq)) {
$type = 'silent';
} else {
$type = 'missense';
}
} else {
$type = 'unknown';
}
} else {
my $len = 0;
$len = CORE::length($o) if $o;
$len -= CORE::length($m) if $m;
if ($len%3 == 0 ) {
$type = 'inframe';
} else {
$type = 'frameshift';
}
if (not $m ) {
$type .= ', '. 'deletion';
}
elsif (not $o ) {
$type .= ', '. 'insertion';
}
else {
$type .= ', '. 'complex';
}
if ($self->codon_ori && $ct->is_ter_codon($self->codon_ori) ) {
$type .= ', '. 'termination codon';
}
}
$self->{'label'} = $type;
return $self->{'label'};
}
=head2 _change_codon_pos
Title : _change_codon_pos
Usage : $newCodonPos = _change_codon_pos($myCodonPos, 5)
Function:
Keeps track of the codon position in a changeing sequence
Returns : codon_pos = integer 1, 2 or 3
Args : valid codon position
signed integer offset to a new location in sequence
=cut
sub _change_codon_pos ($$) {
my ($cpos, $i) = @_;
$cpos = ($cpos + $i%3)%3;
if ($cpos > 3 ) {
$cpos = $cpos - 3;
}
elsif ($cpos < 1 ) {
$cpos = $cpos + 3;
}
return $cpos;
}
1;