# $Id: GeneMap.pm,v 1.17 2006/07/17 14:16:53 sendu Exp $
#
# BioPerl module for Bio::Map::GeneMap
#
# Please direct questions and support issues to <bioperl-l@bioperl.org>
#
# Cared for by Sendu Bala <bix@sendu.me.uk>
#
# Copyright Sendu bala
#
# You may distribute this module under the same terms as perl itself
# POD documentation - main docs before the code
=head1 NAME
Bio::Map::GeneMap - A MapI implementation to represent the area around a gene
=head1 SYNOPSIS
use Bio::Map::GeneMap;
use Bio::Map::Gene;
use Bio::Map::TranscriptionFactor;
use Bio::Map::GeneRelative;
# make some maps that will represent an area around a particular gene in
# particular species (by default, the map represents the area in the genome
# 1000bp upstream of the gene)
my $map1 = Bio::Map::GeneMap->get(-gene => 'BRCA2',
-species => 'human',
-description => 'breast cancer 2, early onset');
my $map2 = Bio::Map::GeneMap->get(-gene => 'BRCA2',
-species => 'mouse');
# model a TF that binds 500bp upstream of the BRCA2 gene in humans and
# 250bp upstream of BRCA2 in mice
my $rel = Bio::Map::GeneRelative->new(-description => "gene start");
my $tf = Bio::Map::TranscriptionFactor->get(-universal_name => 'tf1');
Bio::Map::Position->new(-map => $map1,
-element => $tf,
-start => -500,
-length => 10,
-relative => $rel);
Bio::Map::Position->new(-map => $map2,
-element => $tf,
-start => -250,
-length => 10,
-relative => $rel);
# find out all the things that map near BRCA2 in all species
foreach my $map ($gene->known_maps) {
foreach my $thing ($map->get_elements) {
next if $thing eq $gene;
foreach my $pos ($thing->get_positions($map)) {
print "In species ", $map->species, ", ",
$thing->universal_name, " maps at ", $pos->value,
" relative to ", $pos->relative->description, " of gene ",
$gene->universal_name, "\n";
}
}
}
# a GeneMap isa PrimarySeq and so can have sequence associated with it
$map1->seq('ATGC');
my $subseq = $map1->subseq(2,3); # TG
=head1 DESCRIPTION
Model the abstract notion of the area around a gene - you don't care exactly
where this area is in the genome, you just want to be able to say "something
binds upstream of gene X" and "something else binds 20bp upstream of the first
something" etc.
It's useful for modelling transcription factor bindings sites, letting you find
out which transcription factors bind near a gene of interest, or which genes
are bound by a transcription factor of interest.
See t/Map/Map.t for more example usage.
=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
the Bioperl mailing list. 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
of the bugs and their resolution. Bug reports can be submitted via the
web:
https://redmine.open-bio.org/projects/bioperl/
=head1 AUTHOR - Sendu Bala
Email bix@sendu.me.uk
=head1 APPENDIX
The rest of the documentation details each of the object methods.
Internal methods are usually preceded with a _
=cut
# Let the code begin...
package Bio::Map::GeneMap;
use strict;
use Bio::Map::Gene;
use Bio::Map::Position;
use base qw(Bio::Map::SimpleMap Bio::PrimarySeq);
our $GENEMAPS = {};
=head2 new
Title : new
Usage : my $obj = Bio::Map::GeneMap->new();
Function: Builds a new Bio::Map::GeneMap object (that has placed on it a
mappable element (Bio::Map::Gene) representing a gene).
Returns : Bio::Map::GeneMap
Args : -gene => string name of the gene this map will be for
(in a form common to all species that have the gene,
but unique amongst non-orthologous genes) or a
Bio::Map::Gene object, REQUIRED
-species => Bio::Taxon or string representing species, REQUIRED
-uid => string, unique identifier for this map (must be
unique amongst all gene/species combinations)
-description => string, free text description of the gene
-upstream => int, the number of bases the map extends before the
start of the gene element (default 1000).
-downstream => int, the number of bases the map extends beyond the
end of the gene element (default 0).
-seq => string, the sequence of the map, presumably the
genomic sequence -upstream bases of the gene,
including the gene, and -downstream bases of the gene
=cut
sub new {
my ($class, @args) = @_;
my $self = $class->SUPER::new(@args);
my ($uid, $gene, $species, $desc, $up, $down, $seq) = $self->_rearrange([qw(UID
GENE
SPECIES
DESCRIPTION
UPSTREAM
DOWNSTREAM
SEQ)], @args);
unless (defined $gene && defined $species) {
$self->throw("You must supply both -species and -gene");
}
$self->gene(-gene => $gene, -description => $desc, -upstream => $up, -downstream => $down);
$self->seq($seq) if $seq;
unless (defined($uid)) {
# trigger the special behaviour in our unique_id method by supplying it
# the unique_id we got from our parent class
$self->unique_id($self->unique_id);
}
return $self;
}
=head2 get
Title : get
Usage : my $map = Bio::Map::GeneMap->get();
Function: Builds a new Bio::Map::GeneMap object (like new()), or gets a
pre-existing one that corresponds to your arguments.
Returns : Bio::Map::GeneMap
Args : -gene => string name of the gene this map will be for
(in a form common to all species that have the gene,
but unique amongst non-orthologous genes) or a
Bio::Map::Gene object, REQUIRED
-species => Bio::Taxon or string representing species, REQUIRED
-uid => string, unique identifier for this map (must be
unique amongst all gene/species combinations)
-description => string, free text description of the gene
-upstream => int, the number of bases the map extends before the
start of the gene element (default 1000).
-downstream => int, the number of bases the map extends beyond the
end of the gene element (default 0).
-seq => string, the sequence of the map, presumably the
genomic sequence -upstream bases of the gene,
including the gene, and -downstream bases of the gene
If you supply a -uid, and a map had previously been created and
given that uid, that same map object will be returned. Otherwise, the
combination of -gene and -species will be used to determine
if the same map had previously been made. If a corresponding map
hadn't previously been made, a new map object will be created and
returned.
=cut
sub get {
my ($class, @args) = @_;
my ($uid, $gene, $species, $desc, $up, $down, $seq) = Bio::Root::Root->_rearrange([qw(UID
GENE
SPECIES
DESCRIPTION
UPSTREAM
DOWNSTREAM
SEQ)], @args);
my $gene_map;
if ($uid && defined $GENEMAPS->{by_uid}->{$uid}) {
$gene_map = $GENEMAPS->{by_uid}->{$uid};
}
elsif ($gene && $species) {
my $name = ref($gene) ? $gene->universal_name : $gene;
if (defined $GENEMAPS->{by_ns}->{$name}->{$species}) {
$gene_map = $GENEMAPS->{by_ns}->{$name}->{$species};
}
}
if ($gene_map) {
$gene_map->gene->description($desc) if $desc;
$gene_map->upstream($up) if defined($up);
$gene_map->downstream($down) if defined($down);
$gene_map->seq($seq) if $seq;
return $gene_map;
}
return $class->new(@args);
}
=head2 unique_id
Title : unique_id
Usage : my $id = $map->unique_id;
Function: Get/set the unique ID for this map
Returns : string
Args : none to get, OR string to set
=cut
sub unique_id {
my ($self, $id) = @_;
if (defined $id) {
delete $GENEMAPS->{by_uid}->{$self->{'_uid'}};
$self->{'_uid'} = $id;
$GENEMAPS->{by_uid}->{$id} = $self;
}
return $self->{'_uid'};
}
=head2 species
Title : species
Usage : my $species = $map->species;
Function: Get/set Species for a map. It is not recommended to change this once
set.
Returns : Bio::Taxon object or string
Args : none to get, OR Bio::Taxon or string to set
=cut
sub species {
my ($self, $value) = @_;
if ($value) {
my $old_species = $self->{_species};
$self->{'_species'} = $value;
my $name = $self->universal_name || return $value;
if ($old_species) {
delete $GENEMAPS->{by_ns}->{$name}->{$old_species};
}
$GENEMAPS->{by_ns}->{$name}->{$value} = $self;
}
return $self->{'_species'};
}
=head2 type
Title : type
Usage : my $type = $map->type
Function: Get Map type
Returns : string 'gene'
Args : none
=cut
sub type {
return 'gene';
}
=head2 gene
Title : gene
Usage : my $gene = $map->gene;
$map->gene(-gene => $gene);
Function: Get/set the mappable element on this map that represents the gene
this map is for. Once set, it is not recommended to re-set the gene
to something else. Behaviour in that case is undefined.
Returns : Bio::Map::Gene
Args : none to get, OR to set:
-gene => Bio::Map::Gene or string of the universal name (see
Bio::Map::Gene docs), REQUIRED
-description => string, applied to the Bio::Map::Gene
-upstream => int, the number of bases the map extends before the
start of the gene element (default 1000).
-downstream => int, the number of bases the map extends beyond the
end of the gene element (default 0).
=cut
sub gene {
my ($self, @args) = @_;
if (@args > 0) {
my ($gene, $desc, $up, $down) = $self->_rearrange([qw(GENE
DESCRIPTION
UPSTREAM
DOWNSTREAM)], @args);
$self->throw("You must supply -gene") unless $gene;
my $gene_obj = ref($gene) ? $gene : Bio::Map::Gene->get(-universal_name => $gene, -description => $desc);
if (defined $self->{gene}) {
if ($self->{gene} ne $gene_obj) {
$self->warn("Changing the gene that this map is for, which could be bad");
$self->purge_positions($self->{gene});
delete $GENEMAPS->{by_ns}->{$self->universal_name}->{$self->species};
$self->{gene} = $gene_obj;
}
# change the gene's position on us if necessary
$self->upstream($up) if defined $up;
$self->downstream($down) if defined $down;
}
else {
# give the gene object a position on us
$up ||= 1000;
$up >= 0 || $self->throw("-upstream must be a positive integer");
Bio::Map::Position->new(-map => $self, -start => ($up + 1), -element => $gene_obj);
$self->{gene} = $gene_obj;
$self->downstream($down || 0);
# set other gene positions from db if already user-requested
$gene_obj->_set_from_db($self);
}
$GENEMAPS->{by_ns}->{$self->universal_name}->{$self->species} = $self;
}
return $self->{gene};
}
=head2 universal_name
Title : universal_name
Usage : my $name = $map->universal_name
Function: Get/set the name of Bio::Map::Gene object associated with this map.
It is not recommended to change this once set.
Returns : string
Args : none to get, OR string to set
=cut
sub universal_name {
my ($self, $value) = @_;
$self->gene || return;
if ($value) {
my $species = $self->species;
delete $GENEMAPS->{by_ns}->{$self->gene->universal_name}->{$species};
$self->gene->universal_name($value);
$GENEMAPS->{by_ns}->{$value}->{$species} = $self;
}
return $self->gene->universal_name;
}
=head2 upstream
Title : upstream
Usage : my $distance = $map->upstream;
$map->upstream($distance);
Function: Get/set how long the map is before the start of the Bio::Map::Gene
object on this map.
Returns : int
Args : none to get, OR int to set (the number of bases the map extends
before the start of the gene)
=cut
sub upstream {
my ($self, $value) = @_;
my $pos = $self->gene->position($self);
if (defined($value)) {
$value >= 0 || $self->throw("Supplied value must be a positive integer");
$pos->start($value + 1);
}
return $pos->start - 1;
}
=head2 downstream
Title : downstream
Usage : my $distance = $map->downstream;
$map->downstream($distance);
Function: Get/set the nominal end of the map relative to the end of the
Bio::Map::Gene object on this map.
Returns : int
Args : none to get, OR int to set (the number of bases the map extends
beyond the end of the gene)
=cut
sub downstream {
my $self = shift;
if (@_) { $self->{_downstream} = shift }
return $self->{_downstream} || 0;
}
=head2 length
Title : length
Usage : my $length = $map->length();
Function: Retrieves the length of the map. This is normally the length of the
upstream region + length of the gene + length of the downstream
region, but may be longer if positions have been placed on the map
beyond the end of the nominal downstream region.
Returns : int
Args : none
=cut
sub length {
my $self = shift;
my $expected_length = $self->gene->position($self)->length + $self->upstream + $self->downstream;
my $actual_length = $self->SUPER::length;
return $actual_length > $expected_length ? $actual_length : $expected_length;
}
=head2 seq
Title : seq
Usage : $string = $obj->seq()
Function: Get/set the sequence as a string of letters. When getting, If the
GeneMap object didn't have sequence attached directly to it for the
region requested, the map's gene's database will be asked for the
sequence, and failing that, the map's gene's positions will be asked
for their sequences. Areas for which no sequence could be found will
be filled with Ns, unless no sequence was found anywhere, in which
case undef is returned.
Returns : string
Args : Optionally on set the new value (a string). An optional second
argument presets the alphabet (otherwise it will be guessed).
=cut
sub seq {
my ($self, @args) = @_;
my $seq = $self->SUPER::seq(@args);
my $expected_length = $self->length;
if (! $seq || CORE::length($seq) < $expected_length) {
my @have = split('', $seq || '');
my @result;
for (0..($expected_length - 1)) {
$result[$_] = shift(@have) || 'N';
}
# build map sequence by asking gene or positions
my @slice_stuff = $self->gene->_get_slice($self);
if (@slice_stuff) {
my ($slice_adaptor, $slice, $strand) = @slice_stuff;
my ($start, $end, $gene_start) = (CORE::length($seq || '') + 1, $expected_length, $self->upstream + 1);
# convert map coords to genomic coords
my $adjust = $strand == -1 ? $slice->end : $slice->start;
my $adjustment = sub { return $strand == -1 ? $adjust - shift() : shift() + $adjust; };
my $converted_start = &$adjustment($start - $gene_start);
my $converted_end = &$adjustment($end - $gene_start);
($converted_start, $converted_end) = ($converted_end, $converted_start) if $converted_start > $converted_end;
# get sequence from a new slice of desired region
#*** what happens if desired region starts or ends off end of chromo?...
my $new_slice = $slice_adaptor->fetch_by_region($slice->coord_system_name, $slice->seq_region_name, $converted_start, $converted_end);
if ($new_slice && (my $seq_str = $new_slice->seq)) {
if ($strand == -1) {
$seq_str = $self->_revcom($seq_str);
}
splice(@result, CORE::length($seq || ''), CORE::length($seq_str), split('', $seq_str));
}
}
else {
foreach my $pos ($self->get_positions) {
next unless $pos->can('seq');
my @pos_seq = split('', $pos->seq(undef, undef, 1) || next);
for my $i ($pos->start($pos->absolute_relative)..$pos->end($pos->absolute_relative)) {
$i--;
my $base = shift(@pos_seq);
if ($result[$i] eq 'N') {
$result[$i] = $base;
}
}
}
}
$seq = join('', @result);
}
return $seq;
}
=head2 subseq
Title : subseq
Usage : $substring = $obj->subseq(10, 40);
Function: Returns the subseq from start to end, where the first base
is 1 and the number is inclusive, ie 1-2 are the first two
bases of the sequence. If the GeneMap object didn't have sequence
attached directly to it for the region requested, the map's gene's
database will be asked for the sequence, and failing that, the map's
gene's positions will be asked for their sequences. Areas for which
no sequence could be found will be filled with Ns, unless no
sequence was found anywhere, in which case undef is returned. subseq
requests that extend beyond the end of the map will throw.
Returns : string
Args : integer for start position AND integer for end position
OR
Bio::LocationI location for subseq (strand honored)
OR
Bio::RangeI (eg. a Bio::Map::PositionI)
=cut
sub subseq {
my ($self, $start, $end) = @_;
if ($start && ref($start) && $start->isa('Bio::RangeI')) {
my $thing = $start;
if ($start->isa('Bio::Map::Position')) {
($start, $end) = ($thing->start($thing->absolute_relative), $thing->end($thing->absolute_relative));
}
else {
($start, $end) = ($thing->start, $thing->end);
}
}
# *** this implementation potentially wastefull? Should duplicate code
# from seq() to do this just for the desired region??
my $orig_seq = $self->{seq};
$self->{seq} = $self->seq();
my $subseq = $self->{seq} ? $self->SUPER::subseq($start, $end) : '';
$self->{seq} = $orig_seq;
return $subseq;
}
# quick revcom for strings (silly to create a PrimarySeq just to revcom and then
# return a string again)
sub _revcom {
my ($self, $seq) = @_;
$seq or return;
$seq = reverse($seq);
$seq =~ tr/acgtrymkswhbvdnxACGTRYMKSWHBVDNX/tgcayrkmswdvbhnxTGCAYRKMSWDVBHNX/;
return $seq;
}
1;