#
# BioPerl module for IUPAC
#
# Please direct questions and support issues to <bioperl-l@bioperl.org>
#
# Cared for by Aaron Mackey <amackey@virginia.edu>
#
# Copyright Aaron Mackey
#
# You may distribute this module under the same terms as perl itself
# POD documentation - main docs before the code
=head1 NAME
Bio::Tools::IUPAC - Generates unique sequence objects or regular expressions from
an ambiguous IUPAC sequence
=head1 SYNOPSIS
use Bio::PrimarySeq;
use Bio::Tools::IUPAC;
# Get the IUPAC code for proteins
my %iupac_prot = Bio::Tools::IUPAC->new->iupac_iup;
# Create a sequence with degenerate residues
my $ambiseq = Bio::PrimarySeq->new(-seq => 'ARTCGUTGN', -alphabet => 'dna');
# Create all possible non-degenerate sequences
my $iupac = Bio::Tools::IUPAC->new(-seq => $ambiseq);
while ($uniqueseq = $iupac->next_seq()) {
# process the unique Bio::Seq object.
}
# Get a regular expression that matches all possible sequences
my $regexp = $iupac->regexp();
=head1 DESCRIPTION
Bio::Tools::IUPAC is a tool that manipulates sequences with ambiguous residues
following the IUPAC conventions. Non-standard characters have the meaning
described below:
IUPAC-IUB SYMBOLS FOR NUCLEOTIDE (DNA OR RNA) NOMENCLATURE:
Cornish-Bowden (1985) Nucl. Acids Res. 13: 3021-3030
---------------------------------------------------------------
Symbol Meaning Nucleic Acid
---------------------------------------------------------------
A A Adenine
C C Cytosine
G G Guanine
T T Thymine
U U Uracil
M A or C aMino
R A or G puRine
W A or T Weak
S C or G Strong
Y C or T pYrimidine
K G or T Keto
V A or C or G not T (closest unused char after T)
H A or C or T not G (closest unused char after G)
D A or G or T not C (closest unused char after C)
B C or G or T not A (closest unused char after A)
X G or A or T or C Unknown (very rarely used)
N G or A or T or C Unknown (commonly used)
IUPAC-IUP AMINO ACID SYMBOLS:
Biochem J. 1984 Apr 15; 219(2): 345-373
Eur J Biochem. 1993 Apr 1; 213(1): 2
------------------------------------------
Symbol Meaning
------------------------------------------
A Alanine
B Aspartic Acid, Asparagine
C Cysteine
D Aspartic Acid
E Glutamic Acid
F Phenylalanine
G Glycine
H Histidine
I Isoleucine
J Isoleucine/Leucine
K Lysine
L Leucine
M Methionine
N Asparagine
O Pyrrolysine
P Proline
Q Glutamine
R Arginine
S Serine
T Threonine
U Selenocysteine
V Valine
W Tryptophan
X Unknown
Y Tyrosine
Z Glutamic Acid, Glutamine
* Terminator
There are a few things Bio::Tools::IUPAC can do for you:
=over
=item *
report the IUPAC mapping between ambiguous and non-ambiguous residues
=item *
produce a stream of all possible corresponding unambiguous Bio::Seq objects given
an ambiguous sequence object
=item *
convert an ambiguous sequence object to a corresponding regular expression
=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://redmine.open-bio.org/projects/bioperl/
=head1 AUTHOR - Aaron Mackey
Email amackey-at-virginia.edu
=head1 APPENDIX
The rest of the documentation details each of the object
methods. Internal methods are usually preceded with a _
=cut
package Bio::Tools::IUPAC;
use strict;
use base qw(Bio::Root::Root);
use vars qw(%IUB %IUB_AMB %REV_IUB %IUP %IUP_AMB $AUTOLOAD);
BEGIN {
# Ambiguous nucleic residues are matched to unambiguous residues
%IUB = (
A => [qw(A)],
C => [qw(C)],
G => [qw(G)],
T => [qw(T)],
U => [qw(U)],
M => [qw(A C)],
R => [qw(A G)],
S => [qw(C G)],
W => [qw(A T)],
Y => [qw(C T)],
K => [qw(G T)],
V => [qw(A C G)],
H => [qw(A C T)],
D => [qw(A G T)],
B => [qw(C G T)],
N => [qw(A C G T)],
X => [qw(A C G T)],
);
# Same as %IUB but ambiguous residues are matched to ambiguous residues only
%IUB_AMB = (
M => [qw(M)],
R => [qw(R)],
W => [qw(W)],
S => [qw(S)],
Y => [qw(Y)],
K => [qw(K)],
V => [qw(M R S V)],
H => [qw(H M W Y)],
D => [qw(D K R W)],
B => [qw(B K S Y)],
N => [qw(B D H K M N R S V W Y)],
);
# The inverse of %IUB
%REV_IUB = (
A => 'A',
T => 'T',
U => 'U',
C => 'C',
G => 'G',
AC => 'M',
AG => 'R',
AT => 'W',
CG => 'S',
CT => 'Y',
GT => 'K',
ACG => 'V',
ACT => 'H',
AGT => 'D',
CGT => 'B',
ACGT => 'N',
N => 'N'
);
# Same thing with proteins now
%IUP = (
A => [qw(A)],
B => [qw(D N)],
C => [qw(C)],
D => [qw(D)],
E => [qw(E)],
F => [qw(F)],
G => [qw(G)],
H => [qw(H)],
I => [qw(I)],
J => [qw(I L)],
K => [qw(K)],
L => [qw(L)],
M => [qw(M)],
N => [qw(N)],
O => [qw(O)],
P => [qw(P)],
Q => [qw(Q)],
R => [qw(R)],
S => [qw(S)],
T => [qw(T)],
U => [qw(U)],
V => [qw(V)],
W => [qw(W)],
X => [qw(X)],
Y => [qw(Y)],
Z => [qw(E Q)],
'*' => [qw(*)],
);
%IUP_AMB = (
B => [qw(B)],
J => [qw(J)],
Z => [qw(Z)],
);
}
=head2 new
Title : new
Usage : Bio::Tools::IUPAC->new($seq);
Function: Create a new IUPAC object, which acts as a sequence stream (akin to
SeqIO)
Args : an ambiguously coded sequence object that has a specified 'alphabet'
Returns : a Bio::Tools::IUPAC object.
=cut
sub new {
my ($class,@args) = @_;
my $self = $class->SUPER::new(@args);
my ($seq) = $self->_rearrange([qw(SEQ)],@args);
if ( (not defined $seq) && @args && ref($args[0]) ) {
# parameter not passed as named parameter?
$seq = $args[0];
}
if (defined $seq) {
if (not $seq->isa('Bio::PrimarySeqI')) {
$self->throw('Must supply a sequence object');
}
if (length $seq->seq == 0) {
$self->throw('Sequence had zero-length');
}
$self->{'_seq'} = $seq;
}
return $self;
}
sub _initialize {
my ($self) = @_;
my %iupac = $self->iupac;
$self->{'_alpha'} = [ map { $iupac{uc $_} } split('', $self->{'_seq'}->seq) ];
$self->{'_string'} = [(0) x length($self->{'_seq'}->seq())];
$self->{'_string'}->[0] = -1;
}
=head2 next_seq
Title : next_seq
Usage : $iupac->next_seq();
Function: returns the next unique sequence object
Args : none.
Returns : a Bio::Seq object
=cut
sub next_seq {
my ($self) = @_;
if (not exists $self->{'_string'}) {
$self->_initialize();
}
for my $i ( 0 .. $#{$self->{'_string'}} ) {
next unless $self->{'_string'}->[$i] || @{$self->{'_alpha'}->[$i]} > 1;
if ( $self->{'_string'}->[$i] == $#{$self->{'_alpha'}->[$i]} ) { # rollover
if ( $i == $#{$self->{'_string'}} ) { # end of possibilities
return;
} else {
$self->{'_string'}->[$i] = 0;
next;
}
} else {
$self->{'_string'}->[$i]++;
my $j = -1;
my $seqstr = join('', map { $j++; $self->{'_alpha'}->[$j]->[$_]; } @{$self->{'_string'}});
my $desc = $self->{'_seq'}->desc() || '';
$self->{'_num'}++;
1 while $self->{'_num'} =~ s/(\d)(\d\d\d)(?!\d)/$1,$2/;
$desc =~ s/( \[Bio::Tools::IUPAC-generated\sunique sequence # [^\]]*\])|$/ \[Bio::Tools::IUPAC-generated unique sequence # $self->{'_num'}\]/;
$self->{'_num'} =~ s/,//g;
# Return a fresh sequence object
return Bio::PrimarySeq->new(-seq => $seqstr, -desc => $desc);
}
}
}
=head2 iupac
Title : iupac
Usage : my %symbols = $iupac->iupac;
Function: Returns a hash of symbols -> symbol components of the right type
for the given sequence, i.e. it is the same as iupac_iup() if
Bio::Tools::IUPAC was given a proteic sequence, or iupac_iub() if the
sequence was nucleic. For example, the key 'M' has the value ['A', 'C'].
Args : none
Returns : Hash
=cut
sub iupac {
my ($self) = @_;
my $alphabet = lc( $self->{'_seq'}->alphabet() );
if ( ($alphabet eq 'dna') or ($alphabet eq 'rna') ) {
return %IUB; # nucleic
} elsif ( $alphabet eq 'protein' ) {
return %IUP; # proteic
} else {
$self->throw("The input sequence had the unknown alphabet '$alphabet'\n");
}
}
=head2 iupac_amb
Title : iupac_amb
Usage : my %symbols = $iupac->iupac_amb;
Function: Same as iupac() but only contains a mapping between ambiguous residues
and the ambiguous residues they map to. For example, the key 'N' has
the value ['R', 'Y', 'K', 'M', 'S', 'W', 'B', 'D', 'H', 'V', 'N'],
i.e. it matches all other ambiguous residues.
Args : none
Returns : Hash
=cut
sub iupac_amb {
my ($self) = @_;
my $alphabet = lc( $self->{'_seq'}->alphabet() );
if ( ($alphabet eq 'dna') or ($alphabet eq 'rna') ) {
return %IUB_AMB; # nucleic
} elsif ( $alphabet eq 'protein' ) {
return %IUP_AMB; # proteic
} else {
$self->throw("The input sequence had the unknown alphabet '$alphabet'\n");
}
}
=head2 iupac_iup
Title : iupac_iup
Usage : my %aasymbols = $iupac->iupac_iup;
Function: Returns a hash of PROTEIN symbols -> non-ambiguous symbol components
Args : none
Returns : Hash
=cut
sub iupac_iup {
return %IUP;
}
=head2 iupac_iup_amb
Title : iupac_iup_amb
Usage : my %aasymbols = $iupac->iupac_iup_amb;
Function: Returns a hash of PROTEIN symbols -> ambiguous symbol components
Args : none
Returns : Hash
=cut
sub iupac_iup_amb {
return %IUP_AMB;
}
=head2 iupac_iub
Title : iupac_iub
Usage : my %dnasymbols = $iupac->iupac_iub;
Function: Returns a hash of DNA symbols -> non-ambiguous symbol components
Args : none
Returns : Hash
=cut
sub iupac_iub {
return %IUB;
}
=head2 iupac_iub_amb
Title : iupac_iub_amb
Usage : my %dnasymbols = $iupac->iupac_iub;
Function: Returns a hash of DNA symbols -> ambiguous symbol components
Args : none
Returns : Hash
=cut
sub iupac_iub_amb {
return %IUB_AMB;
}
=head2 iupac_rev_iub
Title : iupac_rev_iub
Usage : my %dnasymbols = $iupac->iupac_rev_iub;
Function: Returns a hash of nucleotide combinations -> IUPAC code
(a reverse of the iupac_iub hash).
Args : none
Returns : Hash
=cut
sub iupac_rev_iub {
return %REV_IUB;
}
=head2 count
Title : count
Usage : my $total = $iupac->count();
Function: Calculates the number of unique, unambiguous sequences that
this ambiguous sequence could generate
Args : none
Return : int
=cut
sub count {
my ($self) = @_;
if (not exists $self->{'_string'}) {
$self->_initialize();
}
my $count = 1;
$count *= scalar(@$_) for (@{$self->{'_alpha'}});
return $count;
}
=head2 regexp
Title : regexp
Usage : my $re = $iupac->regexp();
Function: Converts the ambiguous sequence into a regular expression that
matches all of the corresponding ambiguous and non-ambiguous sequences.
You can further manipulate the resulting regular expression with the
Bio::Tools::SeqPattern module. After you are done building your
regular expression, you might want to compile it and make it case-
insensitive:
$re = qr/$re/i;
Args : 1 to match RNA: T and U characters will match interchangeably
Return : regular expression
=cut
sub regexp {
my ($self, $match_rna) = @_;
my $re;
my $seq = $self->{'_seq'}->seq;
my %iupac = $self->iupac;
my %iupac_amb = $self->iupac_amb;
for my $pos (0 .. length($seq)-1) {
my $res = substr $seq, $pos, 1;
my $iupacs = $iupac{$res};
my $iupacs_amb = $iupac_amb{$res} || [];
if (not defined $iupacs) {
$self->throw("Primer sequence '$seq' is not a valid IUPAC sequence.".
" Offending character was '$res'.\n");
}
my $part = join '', (@$iupacs, @$iupacs_amb);
if ($match_rna) {
$part =~ s/T/TU/i || $part =~ s/U/TU/i;
}
if (length $part > 1) {
$part = '['.$part.']';
}
$re .= $part;
}
return $re;
}
sub AUTOLOAD {
my $self = shift @_;
my $method = $AUTOLOAD;
$method =~ s/.*:://;
return $self->{'_seq'}->$method(@_)
unless $method eq 'DESTROY';
}
1;