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Summary

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

Package variables

Included modules

Inherit

Bio::Variation::VariantI

Synopsis

   $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

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.

Methods

Methods description

 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

 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 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

 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

 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.
           http://www.interscience.wiley.com/jpages/1059-7794/nomenclature.html

 Returns : string

Methods code

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 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 (undef);
      }
      else {
	  $self->{'RNAChange'} = $value;
      }
  }
  unless (exists $self->{'RNAChange'}) {
      return (undef);
  } 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 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 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 undef unless $o and $m and length $o == 1 and length $m == 1;
    return undef 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;

}

General documentation

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Email: heikki@ebi.ac.uk
Address:

     EMBL Outstation, European Bioinformatics Institute
     Wellcome Trust Genome Campus, Hinxton
     Cambs. CB10 1SD, United Kingdom

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