Bio::Variation::RNAChange - Sequence change class for RNA level

   $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);

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 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

 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

 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

 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

 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

 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

 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.

 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

 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    : 

 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

 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

#
# BioPerl module for Bio::Variation::RNAChange
#
# 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::RNAChange;
use strict;

# Object preamble - inheritance

use Bio::Tools::CodonTable;

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,
	$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!
}

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'};
}

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'};
}

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'};
}

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'};
    }
}

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;
	}
	else {
	    $self->{'DNAMutation'} = $value;
	}
    }
    unless (exists $self->{'DNAMutation'}) {
	return;
    } else {
	return $self->{'DNAMutation'};
    }
}

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;
	}
	else {
	    $self->{'AAChange'} = $value;
	}
    }
    unless (exists $self->{'AAChange'}) {
	return;
    } else {
	return $self->{'AAChange'};
    }
}    

sub exons_modified {
  my ($self,$value)=@_;
  if (defined($value)) {
    $self->{'exons_modified'}=$value;
  }
  return ($self->{'exons_modified'});
}

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'};
}

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'};
}

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'};
}

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;