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 <heikki@ebi.ac.uk> # # 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<Bio::Variation::VariantI> 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<Bio::Variation::DNAMutation> and L<Bio::Variation::AAChange> 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 : $obj->label(); Function: Sets and returns mutation event label(s). If value is not set, or no argument is given returns false. Each instantiable subclass of L<Bio::Variation::VariantI> needs to implement this method. Valid values are listed in 'Mutation event controlled vocabulary' in http://www.ebi.ac.uk/mutations/recommendations/mutevent.html. Example : Returns : string Args : string =cut sub label { my ($self) = @_; 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;