Bio::Variation::AAChange - Sequence change class for polypeptides

BioPerl documentation Contained in the BioPerl distribution.

Index

Code Index:

NAME

Top

Bio::Variation::AAChange - Sequence change class for polypeptides

SYNOPSIS

Top

   $aamut = Bio::Variation::AAChange->new
       ('-start'         => $start,
 	'-end'           => $end,
 	'-length'        => $len,
 	'-proof'         => $proof,
 	'-isMutation'    => 1,
 	'-mut_number'    => $mut_number
 	);

   my $a1 = Bio::Variation::Allele->new;
   $a1->seq($ori) if $ori;
   $aamut->allele_ori($a1);
   my $a2 = Bio::Variation::Allele->new;
   $a2->seq($mut) if $mut;
   $aachange->add_Allele($a2);
   $aachange->allele_mut($a2);

   print  "\n";

   # add it to a SeqDiff container object
   $seqdiff->add_Variant($rnachange);

   # and create links to and from RNA level variant objects
   $aamut->RNAChange($rnachange);
   $rnachange->AAChange($rnachange);

DESCRIPTION

Top

The instantiable class Bio::Variation::RNAChange describes basic sequence changes at polypeptide level. It uses methods defined in superclass Bio::Variation::VariantI, see Bio::Variation::VariantI for details.

If the variation described by a AAChange object has a known Bio::Variation::RNAAChange object, create the link with method AAChange(). See Bio::Variation::AAChange for more information.

FEEDBACK

Top

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

Support

Please direct usage questions or support issues to the mailing list:

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.

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://redmine.open-bio.org/projects/bioperl/

AUTHOR - Heikki Lehvaslaiho

Top

Email: heikki-at-bioperl-dot-org

APPENDIX

Top

The rest of the documentation details each of the object methods. Internal methods are usually preceded with a _

RNAChange

 Title   : RNAChange
 Usage   : $mutobj = $self->RNAChange;
         : $mutobj = $self->RNAChange($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

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

similarity_score

 Title   : similarity_score
 Usage   : $self->similarity_score
 Function: Measure for evolutionary conservativeness
           of single amino substitutions. Uses BLOSUM62.
           Negative numbers are noncoservative changes.
 Returns : integer, undef if not single amino acid change

trivname

 Title   : trivname
 Usage   : $self->trivname
 Function: 

           Given a Bio::Variation::AAChange object with linked
           Bio::Variation::RNAChange and Bio::Variation::DNAMutation
           objects, this subroutine creates a string corresponding to
           the 'trivial name' of the mutation. Trivial name is
           specified in Antonorakis & MDI Nomenclature Working Group:
           Human Mutation 11:1-3, 1998.

 Returns : string
BioPerl documentation Contained in the BioPerl distribution. 
#
# BioPerl module for Bio::Variation::AAChange
#
# 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



# Let the code begin...


package Bio::Variation::AAChange;

use vars qw($MATRIX);
use strict;

# Object preamble - inheritance

use base qw(Bio::Variation::VariantI);

BEGIN {

my $matrix = << "__MATRIX__";
#  Matrix made by matblas from blosum62.iij
#  * column uses minimum score
#  BLOSUM Clustered Scoring Matrix in 1/2 Bit Units
#  Blocks Database = /data/blocks_5.0/blocks.dat
#  Cluster Percentage: >= 62
#  Entropy =   0.6979, Expected =  -0.5209
   A  R  N  D  C  Q  E  G  H  I  L  K  M  F  P  S  T  W  Y  V  B  Z  X  *
A  4 -1 -2 -2  0 -1 -1  0 -2 -1 -1 -1 -1 -2 -1  1  0 -3 -2  0 -2 -1  0 -4
R -1  5  0 -2 -3  1  0 -2  0 -3 -2  2 -1 -3 -2 -1 -1 -3 -2 -3 -1  0 -1 -4
N -2  0  6  1 -3  0  0  0  1 -3 -3  0 -2 -3 -2  1  0 -4 -2 -3  3  0 -1 -4
D -2 -2  1  6 -3  0  2 -1 -1 -3 -4 -1 -3 -3 -1  0 -1 -4 -3 -3  4  1 -1 -4
C  0 -3 -3 -3  9 -3 -4 -3 -3 -1 -1 -3 -1 -2 -3 -1 -1 -2 -2 -1 -3 -3 -2 -4
Q -1  1  0  0 -3  5  2 -2  0 -3 -2  1  0 -3 -1  0 -1 -2 -1 -2  0  3 -1 -4
E -1  0  0  2 -4  2  5 -2  0 -3 -3  1 -2 -3 -1  0 -1 -3 -2 -2  1  4 -1 -4
G  0 -2  0 -1 -3 -2 -2  6 -2 -4 -4 -2 -3 -3 -2  0 -2 -2 -3 -3 -1 -2 -1 -4
H -2  0  1 -1 -3  0  0 -2  8 -3 -3 -1 -2 -1 -2 -1 -2 -2  2 -3  0  0 -1 -4
I -1 -3 -3 -3 -1 -3 -3 -4 -3  4  2 -3  1  0 -3 -2 -1 -3 -1  3 -3 -3 -1 -4
L -1 -2 -3 -4 -1 -2 -3 -4 -3  2  4 -2  2  0 -3 -2 -1 -2 -1  1 -4 -3 -1 -4
K -1  2  0 -1 -3  1  1 -2 -1 -3 -2  5 -1 -3 -1  0 -1 -3 -2 -2  0  1 -1 -4
M -1 -1 -2 -3 -1  0 -2 -3 -2  1  2 -1  5  0 -2 -1 -1 -1 -1  1 -3 -1 -1 -4
F -2 -3 -3 -3 -2 -3 -3 -3 -1  0  0 -3  0  6 -4 -2 -2  1  3 -1 -3 -3 -1 -4
P -1 -2 -2 -1 -3 -1 -1 -2 -2 -3 -3 -1 -2 -4  7 -1 -1 -4 -3 -2 -2 -1 -2 -4
S  1 -1  1  0 -1  0  0  0 -1 -2 -2  0 -1 -2 -1  4  1 -3 -2 -2  0  0  0 -4
T  0 -1  0 -1 -1 -1 -1 -2 -2 -1 -1 -1 -1 -2 -1  1  5 -2 -2  0 -1 -1  0 -4
W -3 -3 -4 -4 -2 -2 -3 -2 -2 -3 -2 -3 -1  1 -4 -3 -2 11  2 -3 -4 -3 -2 -4
Y -2 -2 -2 -3 -2 -1 -2 -3  2 -1 -1 -2 -1  3 -3 -2 -2  2  7 -1 -3 -2 -1 -4
V  0 -3 -3 -3 -1 -2 -2 -3 -3  3  1 -2  1 -1 -2 -2  0 -3 -1  4 -3 -2 -1 -4
B -2 -1  3  4 -3  0  1 -1  0 -3 -4  0 -3 -3 -2  0 -1 -4 -3 -3  4  1 -1 -4
Z -1  0  0  1 -3  3  4 -2  0 -3 -3  1 -1 -3 -1  0 -1 -3 -2 -2  1  4 -1 -4
X  0 -1 -1 -1 -2 -1 -1 -1 -1 -1 -1 -1 -1 -1 -2  0  0 -2 -1 -1 -1 -1 -1 -4
* -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4 -4  1
__MATRIX__

    my %blosum = ();
    $matrix =~ /^ +(.+)$/m;
    my @aas = split / +/, $1;
    foreach my $aa (@aas) {
	my $tmp = $aa;
	$tmp = "\\$aa" if $aa eq '*';
	$matrix =~ /^($tmp) +([-+]?\d.*)$/m;
	my @scores = split / +/, $2 if defined $2;
	my $count = 0;
	foreach my $ak (@aas) {
	    $blosum{$aa}->{$aas[$count]} = $scores[$count];
	    $count++;
	}
    }
    sub _matrix;
    $MATRIX = \%blosum;
}

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,  $re_changes,  $region, $region_value,
        $region_dist,
	$numbering,  $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
				  RE_CHANGES
				  REGION
				  REGION_VALUE
				  REGION_DIST
				  NUMBERING
				  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);

    return $self; # success - we hope!
}


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'};
  }
}





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;

    if ($self->start == 1 ) {
	if ($o and substr($o, 0, 1) ne substr($m, 0, 1)) {
	    $type = 'no translation';
	}
	elsif ($o and $m and $o eq $m ) {
	    $type = 'silent';
	}
	# more ...
    }
    elsif ($o and substr($o, 0, 1) eq '*' ) {
	if ($m and substr($o, 0, 1) ne substr($m, 0, 1)) {
	    $type = 'post-elongation';
	}
	elsif ($m and $o eq $m ) {
	    $type = 'silent, conservative';
	}
    }
    elsif ($o and $m and $o eq $m) {
	$type = 'silent, conservative';
    }
    elsif ($m and $m eq '*') {
	$type = 'truncation';
    }
    elsif ($o and $m and $o eq $m) {
	$type = 'silent, conservative';
    }
    elsif (not $m or
	   ($o and $m and  length($o) > length($m) and
	    substr($m, -1, 1) ne '*')) {
	$type = 'deletion';
	if ($o and $m and $o !~ $m and $o !~ $m) {
	    $type .= ', complex';
	}
    }
    elsif (not $o or
	   ($o and $m and length($o) < length($m) and
	    substr($m, -1, 1) ne '*' ) ) {
	$type = 'insertion';
	if ($o and $m and $o !~ $m and $o !~ $m) {
	    $type .= ', complex';
	}
    }
    elsif  ($o and $m and $o ne $m and
	    length $o == 1 and  length $m  == 1 ) {
	$type = 'substitution';
	my $value = $self->similarity_score;
	if (defined $value) {
	    my $cons = ($value < 0) ? 'nonconservative' : 'conservative';
	    $type .= ", ". $cons;
	}
    } else {
	$type = 'out-of-frame translation, truncation';
    }
    $self->{'label'} = $type;
    return $self->{'label'};
}



sub similarity_score {
    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;
    return unless $o and $m and length $o == 1 and length $m == 1;
    return unless $o =~ /[ARNDCQEGHILKMFPSTWYVBZX*]/i and
	$m =~ /[ARNDCQEGHILKMFPSTWYVBZX*]/i;
    return $MATRIX->{"\U$o"}->{"\U$m"};
}



sub trivname {
    my ($self,$value) = @_;
    if( defined $value) {
	$self->{'trivname'} = $value;
    } else {
	my ( $aaori, $aamut,$aamutsymbol, $aatermnumber, $aamutterm) =
	    ('', '', '', '', '');
	my $o = $self->allele_ori->seq if $self->allele_ori and $self->allele_ori->seq;
	#my $m = $self->allele_mut->seq if $self->allele_mut and $self->allele_mut->seq;

	$aaori = substr ($o, 0, 1) if $o;
	$aaori =~ tr/\*/X/;

	my $sep;
	if ($self->isMutation) {
	    $sep = '>';
	} else {
	    $sep = '|';
	}
	my $trivname = $aaori. $self->start;
	$trivname .= $sep if $sep eq '|';

	my @alleles = $self->each_Allele;
	foreach my $allele (@alleles) {
	    my $m = $allele->seq if $allele->seq;

	    $self->allele_mut($allele);
	    #$trivname .=  $sep. uc $m if $m;

	    $aamutterm = substr ($m, -1, 1) if $m;
	    if ($self->RNAChange->label =~ /initiation codon/ and
		( $o and $m and $o ne $m)) {
		$aamut = 'X';
	    }
	    elsif (CORE::length($o) == 1 and CORE::length($m) == 1 ) {
		$aamutsymbol = '';
		$aamut = $aamutterm;
	    }
	    elsif ($self->RNAChange->label =~ /deletion/) {
		$aamutsymbol = 'del';
		if ($aamutterm eq '*') {
		    $aatermnumber = $self->start + length($m) -1;
		    $aamut = 'X'. $aatermnumber;
		}
		if ($self->RNAChange  && $self->RNAChange->label =~ /inframe/){
		    $aamut = '-'. length($self->RNAChange->allele_ori->seq)/3 ;
		}
	    }
	    elsif ($self->RNAChange->label =~ /insertion/) {
		$aamutsymbol = 'ins';
		if (($aamutterm eq '*') && (length($m)-1 != 0)) {
		    $aatermnumber = $self->start + length($m)-1;
		    $aamut =  $aatermnumber. 'X';
		}
		if ($self->RNAChange->label =~ /inframe/){
		    $aamut = '+'. int length($self->RNAChange->allele_mut->seq)/3 ;
		}
	    }
	    elsif ($self->RNAChange->label =~ /complex/ ) {
		my $diff = length($m) - length($o);
		if ($diff >= 0 ) {
		    $aamutsymbol = 'ins';
		} else {
		    $aamutsymbol = 'del' ;
		}
		if (($aamutterm eq '*') && (length($m)-1 != 0)) {
		    $aatermnumber = $self->start + length($m)-1;
		    $aamut =  $aatermnumber. 'X';
		}
		if ($self->RNAChange->label =~ /inframe/){

		    if ($diff >= 0 ) {
			$aamut = '+'. $diff ;
		    } else {
			$aamut =  $diff ;
		    }
		}
	    }
	    elsif ($self->label =~ /truncation/) {
		$aamut = $m;
	    } else {
		$aamutsymbol = '';
		$aamut = $aamutterm;
	    }
	    $aamut =~ tr/\*/X/;
	    $trivname .= $aamutsymbol. $aamut. $sep;
	}
	chop $trivname;
	$self->{'trivname'} = $trivname;
    }
    return $self->{'trivname'};
}

1;