# BioPerl module for Bio::Tools::dpAlign
#
# Please direct questions and support issues to <bioperl-l@bioperl.org>
#
# Cared for by Yee Man Chan <ymc@yahoo.com>
#
# Copyright Yee Man Chan
#
# You may distribute this module under the same terms as perl itself
# POD documentation - main docs before the code
=head1 NAME
Bio::Tools::dpAlign - Perl extension to do pairwise dynamic programming sequence alignment
=head1 SYNOPSIS
use Bio::Tools::dpAlign;
use Bio::SeqIO;
use Bio::SimpleAlign;
use Bio::AlignIO;
use Bio::Matrix::IO;
$seq1 = Bio::SeqIO->new(-file => $ARGV[0], -format => 'fasta');
$seq2 = Bio::SeqIO->new(-file => $ARGV[1], -format => 'fasta');
# create a dpAlign object
# to do global alignment, specify DPALIGN_GLOBAL_MILLER_MYERS
# to do ends-free alignment, specify DPALIGN_ENDSFREE_MILLER_MYERS
$factory = new dpAlign(-match => 3,
-mismatch => -1,
-gap => 3,
-ext => 1,
-alg => Bio::Tools::dpAlign::DPALIGN_LOCAL_MILLER_MYERS);
# actually do the alignment
$out = $factory->pairwise_alignment($seq1->next_seq, $seq2->next_seq);
$alnout = Bio::AlignIO->new(-format => 'pfam', -fh => \*STDOUT);
$alnout->write_aln($out);
# To do protein alignment, set the sequence type to protein
# By default all protein alignments are using BLOSUM62 matrix
# the gap opening cost is 7 and gap extension is 1. These
# values are from ssearch. To use your own custom substitution
# matrix, you can create a Bio::Matrix::MatrixI object.
$parser = Bio::Matrix::IO->new(-format => 'scoring', -file => 'blosum50.mat');
$matrix = $parser->next_matrix;
$factory = Bio::Tools::dpAlign->new(-matrix => $matrix, -alg => Bio::Tools::dpAlign::DPALIGN_LOCAL_MILLERMYERS);
$seq1->alphabet('protein');
$seq2->alphabet('protein');
$out = $factory->pairwise_alignment($seq1->next_seq, $seq2->next_seq);
$alnout->write_aln($out);
# use the factory to make some output
$factory->align_and_show($seq1, $seq2, STDOUT);
# use Phil Green's algorithm to calculate the optimal local
# alignment score between two sequences quickly. It is very
# useful when you are searching a query sequence in a database
# of sequences. Since finding a alignment is more costly
# than just calculating scores, you can save time if you only
# align sequences that have a high alignment score.
# To use this feature, first you call the sequence_profile function
# to obtain the profile of the query sequence.
$profile = $factory->sequence_profile($query);
%scores = ();
# Then use a loop to run a database of sequences against the
# profile to obtain a table of alignment scores
$dbseq = Bio::SeqIO(-file => 'dbseq.fa', -format => 'fasta');
while (defined($seq = $dbseq->next_seq)) {
$scores{$seq->id} = $factory->pairwise_alignment_score($profile, $seq);
}
=head1 DESCRIPTION
Dynamic Programming approach is considered to be the most sensitive
way to align two biological sequences. There are currently three major
types of dynamic programming algorithms: Global Alignment, Local
Alignment and Ends-free Alignment.
Global Alignment compares two sequences in their entirety. By
inserting gaps in the two sequences, it aligns two sequences to
minimize the edit distance as defined by the gap cost function and the
substitution matrix. Global Alignment is generally applied to two
sequences that are very similar in length and content.
Local Alignment instead attempts to find out the subsequences that has
the minimal edit distance among all possible subsequences. It is good
for sequences that has a stretch of subsequences that are similar to
each other.
Ends-free Alignment is a special case of Global Alignment. There are
no gap penalty imposed for the gaps that extended from the end points
of two sequences. Therefore it will be a good application when you
think one sequence is contained by the other or when you think two
sequences overlap each other.
Dynamic Programming was first introduced by Needleman-Wunsch (1970) to
globally align two sequences. The idea of local alignment was later
introduced by Smith-Waterman (1981). Gotoh (1982) improved both
algorithms by introducing auxillary arrays that reduced the time
complexity of the algorithms to O(m*n). Miller-Myers (1988) exploits
the divide-and-conquer idea introduced by Hirschberg (1975) to solve
the affine gap cost dynamic programming using only linear space. At
the time of this writing, it is accepted that Miller-Myers is the
fastest single CPU implementation and using the least memory that is
truly equivalent to original algorithm introduced by
Needleman-Wunsch. According to Aaron Mackey, Phil Green's SWAT
implementation introduced a heuristic that does not consider paths
through the matrix where the score would be less than the gap opening
penalty, yielding a 1.5-2X speedup on most comparisons. to skip the
calculation of some cells. However, his approach is only good for
calculating the minimum edit distance and find out the corresponding
subsequences (aka search phase). Bill Pearson's popular dynamic
programming alignment program SSEARCH uses Phil Green's algorithm to
find the subsequences and then Miller-Myers's algorithm to find the
actual alignment. (aka alignment phase)
The current implementation supports local alignment of either DNA
sequences or protein sequences. It allows you to specify either the
Miller-Myers Global Alignment (DPALIGN_GLOBAL_MILLER_MYERS) or
Miller-Myers Local Alignment (DPALIGN_LOCAL_MILLER_MYERS). For DNA
alignment, you can specify the scores for match, mismatch, gap opening
cost and gap extension cost. For protein alignment, it is using
BLOSUM62 by default. Currently the substitution matrix is not
configurable.
Note: If you supply LocatableSeq objects to pairwise_alignment,
pairwise_alignment_score, align_and_show or sequence_profile and
the sequence supplied contains gaps, these functions will treat
these sequences as if they are without gaps.
=head1 DEPENDENCIES
This package comes with the main bioperl distribution. You also need
to install the lastest bioperl-ext package which contains the XS code
that implements the algorithms. This package won't work if you haven't
compiled the bioperl-ext package.
=head1 TO-DO
=over 3
=item 1.
Basic support for IUPAC code for DNA sequence is now implemented.
X will mismatch any character. T will match U. For others, whenever
there is a possibility for match, it is considered a full match, for
example, W will match B.
=item 2.
Allow custom substitution matrix for DNA. Note that for proteins, you
can now use your own subsitution matirx.
=back
=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 one
of 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
=head2 Support
Please direct usage questions or support issues to the mailing list:
I<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.
=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 the
web:
https://github.com/bioperl/bioperl-live/issues
=head1 AUTHOR
This implementation was written by Yee Man Chan (ymc@yahoo.com).
Copyright (c) 2003 Yee Man Chan. All rights reserved. This program
is free software; you can redistribute it and/or modify it under
the same terms as Perl itself. Special thanks to Aaron Mackey
and WIlliam Pearson for the helpful discussions. [The portion
of code inside pgreen subdirectory was borrowed from ssearch. It
should be distributed in the same terms as ssearch.]
=cut
package Bio::Tools::dpAlign;
use Bio::SimpleAlign;
use base qw(Bio::Tools::AlignFactory);
# Gotoh algorithm as defined in J. Mol. Biol. (1982) 162, 705-708
# use constant DSW_GOTOH => 1;
# Hirschberg's algorithm as defined in Myers & Miller in
# CABIOS, Vol 4, No. 1, 1988, p 11-17
# This algorithm is used in both the search phase and the
# alignment phase.
use constant DPALIGN_LOCAL_MILLER_MYERS => 1;
use constant DPALIGN_GLOBAL_MILLER_MYERS => 2;
use constant DPALIGN_ENDSFREE_MILLER_MYERS => 3;
# my toy algorithm that tries to do SW as fast as possible
# use constant DSW_FSW => 3;
# Phil Green's approximation to Smith-Waterman. It avoid calculations
# that might result in a score less than the opening gap penalty.
# This is the algorithm used by ssearch. Phil Green's algorithm is
# used in the search phase while Miller-Myers algorithm is used in
# the alignment phase
#use constant DPALIGN_LOCAL_GREEN => 2;
BEGIN {
eval {
require Bio::Ext::Align;
};
if ( $@ ) {
die("\nThe C-compiled engine for Smith Waterman alignments (Align) has not been installed.\n Please read the install the bioperl-ext package\n\n");
exit(1);
}
}
sub new {
my ($class, @args) = @_;
my $self = $class->SUPER::new(@args);
my ($match, $mismatch, $gap, $ext, $alg, $matrix) = $self->_rearrange([qw(MATCH
MISMATCH
GAP
EXT
ALG
MATRIX
)], @args);
$self->match(3) unless defined $match;
$self->mismatch(-1) unless defined $mismatch;
$self->gap(3) unless defined $gap;
$self->ext(1) unless defined $ext;
$self->alg(DPALIGN_LOCAL_MILLER_MYERS) unless defined $alg;
if (defined $match) {
if ($match =~ /^\d+$/) {
$self->match($match);
}
else {
$self->throw("Match score must be a number, not [$match]");
}
}
if (defined $mismatch) {
if ($match =~ /^\d+$/) {
$self->mismatch($mismatch);
}
else {
$self->throw("Mismatch penalty must be a number, not [$mismatch]");
}
}
if (defined $gap) {
if ($gap =~ /^\d+$/) {
$self->gap($gap);
}
else {
$self->throw("Gap penalty must be a number, not [$gap]");
}
}
if (defined $ext) {
if ($ext =~ /^\d+$/) {
$self->ext($ext);
}
else {
$self->throw("Extension penalty must be a number, not [$ext]");
}
}
if (defined $alg) {
if ($alg == DPALIGN_LOCAL_MILLER_MYERS or $alg == DPALIGN_GLOBAL_MILLER_MYERS or $alg == DPALIGN_ENDSFREE_MILLER_MYERS) {
$self->alg($alg);
}
else {
$self->throw("Algorithm must be either 1, 2 or 3");
}
}
if (defined $matrix and $matrix->isa('Bio::Matrix::MatrixI')) {
$self->{'matrix'} = Bio::Ext::Align::ScoringMatrix->new(join("", $matrix->row_names), $self->gap, $self->ext);
foreach $rowname ($matrix->row_names) {
foreach $colname ($matrix->column_names) {
Bio::Ext::Align::ScoringMatrix->set_entry($self->{'matrix'}, $rowname, $colname, $matrix->entry($rowname, $colname));
}
}
}
else {
$self->{'matrix'} = 0;
}
return $self;
}
=head2 sequence_profile
Title : sequence_profile
Usage : $prof = $factory->sequence_profile($seq1)
Function: Makes a dpAlign_SequenceProfile object from one sequence
Returns : A dpAlign_SequenceProfile object
Args : The lone argument is a Bio::PrimarySeqI that we want to
build a profile for. Usually, this would be the Query sequence
=cut
sub sequence_profile {
my ($self, $seq1) = @_;
if( ! defined $seq1 || ! $seq1->isa('Bio::PrimarySeqI')) {
$self->warn("Cannot call sequence_profilewithout specifing one sequence (Bio::PrimarySeqI object)");
return;
}
# fix Jitterbug #1044
if( $seq1->length() < 2) {
$self->warn("cannot create sequence profile with length less than 2");
return;
}
if ($seq1->isa('Bio::LocatableSeq')) {
my $seqstr = $seq1->seq;
$seqstr =~ s/\-//g;
$seq1 = Bio::Seq->new(-id => $seq1->id, -seq => $seqstr, -alphabet => $seq1->alphabet);
}
# create engine objects
$seq1->display_id('seq1') unless ( defined $seq1->id() );
if ($seq1->alphabet eq 'dna') {
return Bio::Ext::Align::SequenceProfile->dna_new($seq1->seq, $self->{'match'}, $self->{'mismatch'}, $self->{'gap'}, $self->{'ext'});
}
elsif ($seq1->alphabet eq 'protein') {
return Bio::Ext::Align::SequenceProfile->protein_new($seq1->seq, $self->{'matrix'});
}
else {
croak("There is currently no support for the types of sequences you want to align!\n");
return;
}
}
=head2 pairwise_alignment_score
Title : pairwise_alignment_score
Usage : $score = $factory->pairwise_alignment_score($prof,$seq2)
Function: Makes a SimpleAlign object from two sequences
Returns : An integer that is the score of the optimal alignment.
Args : The first argument is the sequence profile obtained from a
call to the sequence_profile function. The second argument
is a Bio::PrimarySeqI object to be aligned. The second argument
is usually a sequence in the database sequence. Note
that this function only uses Phil Green's algorithm and
therefore theoretically may not always give you the optimal
score.
=cut
sub pairwise_alignment_score {
my ($self, $prof, $seq2) = @_;
if( ! defined $prof || ! $prof->isa('Bio::Ext::Align::SequenceProfile') ||
! defined $seq2 || ! $seq2->isa('Bio::PrimarySeqI') ) {
$self->warn("Cannot call pairwise_alignment_score without specifing 2 sequences (Bio::PrimarySeqI objects)");
return;
}
# fix Jitterbug #1044
if( $seq2->length() < 2) {
$self->warn("cannot align sequences with length less than 2");
return;
}
if ($seq2->isa('Bio::LocatableSeq')) {
my $seqstr = $seq2->seq;
$seqstr =~ s/\-//g;
$seq2 = Bio::Seq->new(-id => $seq2->id, -seq => $seqstr, -alphabet => $seq2->alphabet);
}
$self->set_memory_and_report();
# create engine objects
$seq2->display_id('seq2') unless ( defined $seq2->id() );
if ($prof->alphabet eq 'dna' and $seq2->alphabet eq 'dna') {
return Bio::Ext::Align::Score_DNA_Sequences($prof, $seq2->seq);
}
elsif ($prof->alphabet eq 'protein' and $seq2->alphabet eq 'protein') {
return Bio::Ext::Align::Score_Protein_Sequences($prof, $seq2->seq);
}
else {
$self->throw("There is currently no support for the types of sequences you want to align!\n");
return;
}
}
=head2 pairwise_alignment
Title : pairwise_alignment
Usage : $aln = $factory->pairwise_alignment($seq1,$seq2)
Function: Makes a SimpleAlign object from two sequences
Returns : A SimpleAlign object if there is an alignment with positive
score. Otherwise, return undef.
Args : The first and second arguments are both Bio::PrimarySeqI
objects that are to be aligned.
=cut
sub pairwise_alignment {
my ($self, $seq1, $seq2) = @_;
my ($aln, $out);
if( ! defined $seq1 || ! $seq1->isa('Bio::PrimarySeqI') ||
! defined $seq2 || ! $seq2->isa('Bio::PrimarySeqI') ) {
$self->warn("Cannot call pairwise_alignment without specifing 2 sequences (Bio::PrimarySeqI objects)");
return;
}
# fix Jitterbug #1044
if( $seq1->length() < 2 ||
$seq2->length() < 2 ) {
$self->warn("cannot align sequences with length less than 2");
return;
}
if ($seq1->isa('Bio::LocatableSeq')) {
my $seqstr = $seq1->seq;
$seqstr =~ s/\-//g;
$seq1 = Bio::Seq->new(-id => $seq1->id, -seq => $seqstr, -alphabet => $seq1->alphabet);
}
if ($seq2->isa('Bio::LocatableSeq')) {
my $seqstr = $seq2->seq;
$seqstr =~ s/\-//g;
$seq2 = Bio::Seq->new(-id => $seq2->id, -seq => $seqstr, -alphabet => $seq2->alphabet);
}
$self->set_memory_and_report();
# create engine objects
$seq1->display_id('seq1') unless ( defined $seq1->id() );
$seq2->display_id('seq2') unless ( defined $seq2->id() );
if ($seq1->alphabet eq 'dna' and $seq2->alphabet eq 'dna') {
$aln = Bio::Ext::Align::Align_DNA_Sequences($seq1->seq, $seq2->seq, $self->{'match'}, $self->{'mismatch'}, $self->{'gap'}, $self->{'ext'}, $self->{'alg'});
}
elsif ($seq1->alphabet eq 'protein' and $seq2->alphabet eq 'protein') {
$aln = Bio::Ext::Align::Align_Protein_Sequences($seq1->seq, $seq2->seq, $self->{'matrix'}, $self->{'alg'});
}
else {
croak("There is currently no support for the types of sequences you want to align!\n");
return;
}
if (not defined $aln or $aln == 0) {
return;
}
$out = Bio::SimpleAlign->new();
$out->add_seq(Bio::LocatableSeq->new(-seq => $aln->aln1,
-start => $aln->start1,
-end => $aln->end1,
-id => $seq1->id));
$out->add_seq(Bio::LocatableSeq->new(-seq => $aln->aln2,
-start => $aln->start2,
-end => $aln->end2,
-id => $seq2->id));
$out->score($aln->score);
return $out;
}
=head2 align_and_show
Title : align_and_show
Usage : $factory->align_and_show($seq1,$seq2,STDOUT)
=cut
sub align_and_show {
my ($self, $seq1, $seq2, $fh) = @_;
my ($aln, $out);
if (! defined $fh) {
$fh = \*STDOUT;
}
if( ! defined $seq1 || ! $seq1->isa('Bio::PrimarySeqI') ||
! defined $seq2 || ! $seq2->isa('Bio::PrimarySeqI') ) {
$self->warn("Cannot call pairwise_alignment without specifing 2 sequences (Bio::PrimarySeqI objects)");
return;
}
# fix Jitterbug #1044
if( $seq1->length() < 2 ||
$seq2->length() < 2 ) {
$self->warn("cannot align sequences with length less than 2");
return;
}
if ($seq1->isa('Bio::LocatableSeq')) {
my $seqstr = $seq1->seq;
$seqstr =~ s/\-//g;
$seq1 = Bio::Seq->new(-id => $seq1->id, -seq => $seqstr, -alphabet => $seq1->alphabet);
}
if ($seq2->isa('Bio::LocatableSeq')) {
my $seqstr = $seq2->seq;
$seqstr =~ s/\-//g;
$seq2 = Bio::Seq->new(-id => $seq2->id, -seq => $seqstr, -alphabet => $seq2->alphabet);
}
$self->set_memory_and_report();
# create engine objects
$seq1->display_id('seq1') unless ( defined $seq1->id() );
$seq2->display_id('seq2') unless ( defined $seq2->id() );
if ($seq1->alphabet eq 'dna' and $seq2->alphabet eq 'dna') {
$aln = Bio::Ext::Align::Align_DNA_Sequences($seq1->seq, $seq2->seq, $self->{'match'}, $self->{'mismatch'}, $self->{'gap'}, $self->{'ext'}, $self->{'alg'});
}
elsif ($seq1->alphabet eq 'protein' and $seq2->alphabet eq 'protein') {
$aln = Bio::Ext::Align::Align_Protein_Sequences($seq1->seq, $seq2->seq, $self->{'matrix'}, $self->{'alg'});
}
else {
croak("There is currently no support for the types of sequences you want to align!\n");
}
$out = Bio::Ext::Align::AlnBlock->new();
my $s1 = Bio::Ext::Align::AlnSequence->new();
my $s2 = Bio::Ext::Align::AlnSequence->new();
my $a1 = $aln->aln1;
my $a2 = $aln->aln2;
my $first_col = undef;
my $last_col = undef;
my $col;
my $alu1;
my $alu2;
my $g1 = 0;
my $g2 = 0;
# construct AlnBlock
for (my $i = 0; $i < length($a1); ++$i) {
$col = Bio::Ext::Align::AlnColumn->new();
$alu1 = Bio::Ext::Align::AlnUnit->new();
$alu2 = Bio::Ext::Align::AlnUnit->new();
$first_col = $col unless defined $first_col;
Bio::Ext::Align::AlnColumn::set_next($last_col, $col) if defined $last_col;
if (substr($a1, $i, 1) eq "-") {
Bio::Ext::Align::AlnUnit::set_text_label($alu1, "INSERT");
Bio::Ext::Align::AlnUnit::set_text_label($alu2, "SEQUENCE");
++$g1;
}
elsif (substr($a2, $i, 1) eq "-") {
Bio::Ext::Align::AlnUnit::set_text_label($alu1, "SEQUENCE");
Bio::Ext::Align::AlnUnit::set_text_label($alu2, "INSERT");
++$g2;
}
else {
Bio::Ext::Align::AlnUnit::set_text_label($alu1, "SEQUENCE");
Bio::Ext::Align::AlnUnit::set_text_label($alu2, "SEQUENCE");
}
Bio::Ext::Align::AlnUnit::set_start($alu1, $aln->start1+$i-$g1-2);
Bio::Ext::Align::AlnUnit::set_end($alu1, $aln->start1+$i-$g1-2);
Bio::Ext::Align::AlnUnit::set_start($alu2, $aln->start2+$i-$g2-2);
Bio::Ext::Align::AlnUnit::set_end($alu2, $aln->start2+$i-$g2-2);
Bio::Ext::Align::AlnColumn::add_alu($col, $alu1);
Bio::Ext::Align::AlnColumn::add_alu($col, $alu2);
$last_col = $col;
}
Bio::Ext::Align::AlnBlock::set_start($out, $first_col);
$col = Bio::Ext::Align::AlnColumn->new();
$alu1 = Bio::Ext::Align::AlnUnit->new();
$alu2 = Bio::Ext::Align::AlnUnit->new();
Bio::Ext::Align::AlnUnit::set_start($alu1, $aln->end1);
Bio::Ext::Align::AlnUnit::set_end($alu1, $aln->end1);
Bio::Ext::Align::AlnUnit::set_text_label($alu1, "END");
Bio::Ext::Align::AlnUnit::set_start($alu2, $aln->end2);
Bio::Ext::Align::AlnUnit::set_end($alu2, $aln->end2);
Bio::Ext::Align::AlnUnit::set_text_label($alu2, "END");
Bio::Ext::Align::AlnColumn::add_alu($col, $alu1);
Bio::Ext::Align::AlnColumn::add_alu($col, $alu2);
Bio::Ext::Align::AlnColumn::set_next($last_col, $col);
&Bio::Ext::Align::write_pretty_str_align($out,$seq1->id,$seq1->seq,$seq2->id,$seq2->seq,12,50,$fh);
}
=head2 match
Title : match
Usage : $match = $factory->match() #get
: $factory->match($value) #set
Function : the set get for the match score
Example :
Returns : match value
Arguments : new value
=cut
sub match {
my ($self,$val) = @_;
if( defined $val ) {
if( $val < 0 ) { # Fixed so that match==0 is allowed /AE
$self->throw("Can't have a match score less than 0");
}
$self->{'match'} = $val;
}
return $self->{'match'};
}
=head2 mismatch
Title : mismatch
Usage : $mismatch = $factory->mismatch() #get
: $factory->mismatch($value) #set
Function : the set get for the mismatch penalty
Example :
Returns : mismatch value
Arguments : new value
=cut
sub mismatch {
my ($self,$val) = @_;
if( defined $val ) {
if( $val > 0 ) { # Fixed so that mismatch==0 is allowed /AE
$self->throw("Can't have a mismatch penalty greater than 0");
}
$self->{'mismatch'} = $val;
}
return $self->{'mismatch'};
}
=head2 gap
Title : gap
Usage : $gap = $factory->gap() #get
: $factory->gap($value) #set
Function : the set get for the gap penalty
Example :
Returns : gap value
Arguments : new value
=cut
sub gap {
my ($self,$val) = @_;
if( defined $val ) {
if( $val < 0 ) { # Fixed so that gap==0 is allowed /AE
$self->throw("Can't have a gap penalty less than 0");
}
$self->{'gap'} = $val;
}
return $self->{'gap'};
}
=head2 ext
Title : ext
Usage : $ext = $factory->ext() #get
: $factory->ext($value) #set
Function : the set get for the ext penalty
Example :
Returns : ext value
Arguments : new value
=cut
sub ext {
my ($self,$val) = @_;
if( defined $val ) {
if( $val < 0 ) { # Fixed so that ext==0 is allowed /AE
$self->throw("Can't have a extension penalty less than 0");
}
$self->{'ext'} = $val;
}
return $self->{'ext'};
}
=head2 alg
Title : alg
Usage : $alg = $factory->alg() #get
: $factory->alg($value) #set
Function : the set get for the algorithm
Example :
Returns : alg value
Arguments : new value
=cut
sub alg {
my ($self,$val) = @_;
if( defined $val ) {
if( $val != DPALIGN_LOCAL_MILLER_MYERS and $val != DPALIGN_GLOBAL_MILLER_MYERS and $val != DPALIGN_ENDSFREE_MILLER_MYERS) {
$self->throw("Can't have an algorithm that is not 1, 2 or 3");
}
$self->{'alg'} = $val;
}
return $self->{'alg'};
}
1;