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1 =head1 LICENSE
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2
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3 Copyright (c) 1999-2012 The European Bioinformatics Institute and
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4 Genome Research Limited. All rights reserved.
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5
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6 This software is distributed under a modified Apache license.
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7 For license details, please see
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8
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9 http://www.ensembl.org/info/about/code_licence.html
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10
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11 =head1 CONTACT
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12
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13 Please email comments or questions to the public Ensembl
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14 developers list at <dev@ensembl.org>.
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15
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16 Questions may also be sent to the Ensembl help desk at
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17 <helpdesk@ensembl.org>.
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18
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19 =cut
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20
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21 =head1 NAME
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22
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23 Bio::EnsEMBL::IdMapping::SyntenyFramework - framework representing syntenic
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24 regions across the genome
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25
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26 =head1 SYNOPSIS
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27
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28 # build the SyntenyFramework from unambiguous gene mappings
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29 my $sf = Bio::EnsEMBL::IdMapping::SyntenyFramework->new(
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30 -DUMP_PATH => $dump_path,
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31 -CACHE_FILE => 'synteny_framework.ser',
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32 -LOGGER => $self->logger,
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33 -CONF => $self->conf,
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34 -CACHE => $self->cache,
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35 );
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36 $sf->build_synteny($gene_mappings);
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37
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38 # use it to rescore the genes
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39 $gene_scores = $sf->rescore_gene_matrix_lsf($gene_scores);
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40
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41 =head1 DESCRIPTION
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42
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43 The SyntenyFramework is a set of SyntenyRegions. These are pairs of
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44 locations very analoguous to the information in the assembly table (the
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45 locations dont have to be the same length though). They are built from
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46 genes that map uniquely between source and target.
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47
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48 Once built, the SyntenyFramework is used to score source and target gene
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49 pairs to determine whether they are similar. This process is slow (it
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50 involves testing all gene pairs against all SyntenyRegions), this module
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51 therefor has built-in support to run the process in parallel via LSF.
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52
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53 =head1 METHODS
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54
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55 new
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56 build_synteny
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57 _by_overlap
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58 add_SyntenyRegion
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59 get_all_SyntenyRegions
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60 rescore_gene_matrix_lsf
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61 rescore_gene_matrix
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62 logger
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63 conf
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64 cache
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65
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66 =cut
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67
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68 package Bio::EnsEMBL::IdMapping::SyntenyFramework;
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69
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70 use strict;
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71 use warnings;
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72 no warnings 'uninitialized';
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73
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74 use Bio::EnsEMBL::IdMapping::Serialisable;
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75 our @ISA = qw(Bio::EnsEMBL::IdMapping::Serialisable);
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76
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77 use Bio::EnsEMBL::Utils::Argument qw(rearrange);
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78 use Bio::EnsEMBL::Utils::Exception qw(throw warning);
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79 use Bio::EnsEMBL::Utils::ScriptUtils qw(path_append);
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80 use Bio::EnsEMBL::IdMapping::SyntenyRegion;
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81 use Bio::EnsEMBL::IdMapping::ScoredMappingMatrix;
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82
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83 use FindBin qw($Bin);
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84 FindBin->again;
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85
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86
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87 =head2 new
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88
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89 Arg [LOGGER]: Bio::EnsEMBL::Utils::Logger $logger - a logger object
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90 Arg [CONF] : Bio::EnsEMBL::Utils::ConfParser $conf - a configuration object
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91 Arg [CACHE] : Bio::EnsEMBL::IdMapping::Cache $cache - a cache object
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92 Arg [DUMP_PATH] : String - path for object serialisation
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93 Arg [CACHE_FILE] : String - filename of serialised object
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94 Example : my $sf = Bio::EnsEMBL::IdMapping::SyntenyFramework->new(
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95 -DUMP_PATH => $dump_path,
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96 -CACHE_FILE => 'synteny_framework.ser',
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97 -LOGGER => $self->logger,
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98 -CONF => $self->conf,
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99 -CACHE => $self->cache,
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100 );
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101 Description : Constructor.
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102 Return type : Bio::EnsEMBL::IdMapping::SyntenyFramework
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103 Exceptions : thrown on wrong or missing arguments
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104 Caller : InternalIdMapper plugins
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105 Status : At Risk
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106 : under development
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107
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108 =cut
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109
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110 sub new {
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111 my $caller = shift;
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112 my $class = ref($caller) || $caller;
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113 my $self = $class->SUPER::new(@_);
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114
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115 my ($logger, $conf, $cache) = rearrange(['LOGGER', 'CONF', 'CACHE'], @_);
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116
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117 unless ($logger and ref($logger) and
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118 $logger->isa('Bio::EnsEMBL::Utils::Logger')) {
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119 throw("You must provide a Bio::EnsEMBL::Utils::Logger for logging.");
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120 }
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121
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122 unless ($conf and ref($conf) and
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123 $conf->isa('Bio::EnsEMBL::Utils::ConfParser')) {
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124 throw("You must provide configuration as a Bio::EnsEMBL::Utils::ConfParser object.");
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125 }
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126
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127 unless ($cache and ref($cache) and
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128 $cache->isa('Bio::EnsEMBL::IdMapping::Cache')) {
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129 throw("You must provide configuration as a Bio::EnsEMBL::IdMapping::Cache object.");
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130 }
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131
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132 # initialise
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133 $self->logger($logger);
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134 $self->conf($conf);
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135 $self->cache($cache);
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136 $self->{'cache'} = [];
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137
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138 return $self;
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139 }
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140
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141
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142 =head2 build_synteny
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143
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144 Arg[1] : Bio::EnsEMBL::IdMapping::MappingList $mappings - gene mappings
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145 to build the SyntenyFramework from
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146 Example : $synteny_framework->build_synteny($gene_mappings);
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147 Description : Builds the SyntenyFramework from unambiguous gene mappings.
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148 SyntenyRegions are allowed to overlap. At most two overlapping
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149 SyntenyRegions are merged (otherwise we'd get too large
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150 SyntenyRegions with little information content).
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151 Return type : none
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152 Exceptions : thrown on wrong or missing argument
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153 Caller : InternalIdMapper plugins
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154 Status : At Risk
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155 : under development
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156
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157 =cut
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158
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159 sub build_synteny {
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160 my $self = shift;
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161 my $mappings = shift;
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162
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163 unless ($mappings and
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164 $mappings->isa('Bio::EnsEMBL::IdMapping::MappingList')) {
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165 throw('Need a gene Bio::EnsEMBL::IdMapping::MappingList.');
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166 }
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167
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168 # create a synteny region for each mapping
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169 my @synteny_regions = ();
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170
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171 foreach my $entry (@{ $mappings->get_all_Entries }) {
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172
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173 my $source_gene = $self->cache->get_by_key('genes_by_id', 'source',
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174 $entry->source);
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175 my $target_gene = $self->cache->get_by_key('genes_by_id', 'target',
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176 $entry->target);
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177
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178 my $sr = Bio::EnsEMBL::IdMapping::SyntenyRegion->new_fast([
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179 $source_gene->start,
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180 $source_gene->end,
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181 $source_gene->strand,
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182 $source_gene->seq_region_name,
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183 $target_gene->start,
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184 $target_gene->end,
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185 $target_gene->strand,
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186 $target_gene->seq_region_name,
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187 $entry->score,
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188 ]);
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189
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190 push @synteny_regions, $sr;
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191 }
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192
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193 unless (@synteny_regions) {
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194 $self->logger->warning("No synteny regions could be identified.\n");
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195 return;
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196 }
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197
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198 # sort synteny regions
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199 #my @sorted = sort _by_overlap @synteny_regions;
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200 my @sorted = reverse sort {
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201 $a->source_seq_region_name cmp $b->source_seq_region_name ||
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202 $a->source_start <=> $b->source_start ||
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203 $a->source_end <=> $b->source_end } @synteny_regions;
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204
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205 $self->logger->info("SyntenyRegions before merging: ".scalar(@sorted)."\n");
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206
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207 # now create merged regions from overlapping syntenies, but only merge a
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208 # maximum of 2 regions (otherwise you end up with large synteny blocks which
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209 # won't contain much information in this context)
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210 my $last_merged = 0;
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211 my $last_sr = shift(@sorted);
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212
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213 while (my $sr = shift(@sorted)) {
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214 #$self->logger->debug("this ".$sr->to_string."\n");
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215
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216 my $merged_sr = $last_sr->merge($sr);
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217
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218 if (! $merged_sr) {
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219 unless ($last_merged) {
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220 $self->add_SyntenyRegion($last_sr->stretch(2));
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221 #$self->logger->debug("nnn ".$last_sr->to_string."\n");
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222 }
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223 $last_merged = 0;
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224 } else {
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225 $self->add_SyntenyRegion($merged_sr->stretch(2));
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226 #$self->logger->debug("mmm ".$merged_sr->to_string."\n");
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227 $last_merged = 1;
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228 }
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229
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230 $last_sr = $sr;
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231 }
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232
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233 # deal with last synteny region in @sorted
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234 unless ($last_merged) {
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235 $self->add_SyntenyRegion($last_sr->stretch(2));
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236 $last_merged = 0;
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237 }
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238
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239 #foreach my $sr (@{ $self->get_all_SyntenyRegions }) {
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240 # $self->logger->debug("SRs ".$sr->to_string."\n");
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241 #}
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242
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243 $self->logger->info("SyntenyRegions after merging: ".scalar(@{ $self->get_all_SyntenyRegions })."\n");
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244
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245 }
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246
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247
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248 #
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249 # sort SyntenyRegions by overlap
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250 #
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251 sub _by_overlap {
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252 # first sort by seq_region
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253 my $retval = ($b->source_seq_region_name cmp $a->source_seq_region_name);
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254 return $retval if ($retval);
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255
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256 # then sort by overlap:
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257 # return -1 if $a is downstream, 1 if it's upstream, 0 if they overlap
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258 if ($a->source_end < $b->source_start) { return 1; }
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259 if ($a->source_start < $b->source_end) { return -1; }
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260 return 0;
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261 }
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262
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263
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264 =head2 add_SyntenyRegion
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265
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266 Arg[1] : Bio::EnsEMBL::IdMaping::SyntenyRegion - SyntenyRegion to add
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267 Example : $synteny_framework->add_SyntenyRegion($synteny_region);
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268 Description : Adds a SyntenyRegion to the framework. For speed reasons (and
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269 since this is an internal method), no argument check is done.
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270 Return type : none
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271 Exceptions : none
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272 Caller : internal
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273 Status : At Risk
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274 : under development
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275
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276 =cut
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277
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278 sub add_SyntenyRegion {
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279 push @{ $_[0]->{'cache'} }, $_[1];
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280 }
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281
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282
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283 =head2 get_all_SyntenyRegions
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284
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285 Example : foreach my $sr (@{ $sf->get_all_SyntenyRegions }) {
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286 # do something with the SyntenyRegion
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287 }
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288 Description : Get a list of all SyntenyRegions in the framework.
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289 Return type : Arrayref of Bio::EnsEMBL::IdMapping::SyntenyRegion
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290 Exceptions : none
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291 Caller : general
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292 Status : At Risk
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293 : under development
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294
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295 =cut
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296
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297 sub get_all_SyntenyRegions {
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298 return $_[0]->{'cache'};
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299 }
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300
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301
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302 =head2 rescore_gene_matrix_lsf
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303
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304 Arg[1] : Bio::EnsEMBL::IdMapping::ScoredmappingMatrix $matrix - gene
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305 scores to rescore
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306 Example : my $new_scores = $sf->rescore_gene_matrix_lsf($gene_scores);
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307 Description : This method runs rescore_gene_matrix() (via the
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308 synteny_resocre.pl script) in parallel with lsf, then combines
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309 the results to return a single rescored scoring matrix.
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310 Parallelisation is done by chunking the scoring matrix into
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311 several pieces (determined by the --synteny_rescore_jobs
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312 configuration option).
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313 Return type : Bio::EnsEMBL::IdMapping::ScoredMappingMatrix
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314 Exceptions : thrown on wrong or missing argument
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315 thrown on filesystem I/O error
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316 thrown on failure of one or mor lsf jobs
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317 Caller : InternalIdMapper plugins
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318 Status : At Risk
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319 : under development
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320
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321 =cut
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322
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323 sub rescore_gene_matrix_lsf {
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324 my $self = shift;
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325 my $matrix = shift;
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326
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327 unless ($matrix and
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328 $matrix->isa('Bio::EnsEMBL::IdMapping::ScoredMappingMatrix')) {
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329 throw('Need a Bio::EnsEMBL::IdMapping::ScoredMappingMatrix.');
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330 }
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331
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332 # serialise SyntenyFramework to disk
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333 $self->logger->debug("Serialising SyntenyFramework...\n", 0, 'stamped');
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334 $self->write_to_file;
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335 $self->logger->debug("Done.\n", 0, 'stamped');
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336
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337 # split the ScoredMappingMatrix into chunks and write to disk
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338 my $matrix_size = $matrix->size;
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339 $self->logger->debug("Scores before rescoring: $matrix_size.\n");
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340
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341 my $num_jobs = $self->conf->param('synteny_rescore_jobs') || 20;
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342 $num_jobs++;
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343
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344 my $dump_path = path_append($self->conf->param('basedir'),
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345 'matrix/synteny_rescore');
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346
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347 $self->logger->debug("Creating sub-matrices...\n", 0, 'stamped');
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348 foreach my $i (1..$num_jobs) {
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349 my $start = (int($matrix_size/($num_jobs-1)) * ($i - 1)) + 1;
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350 my $end = int($matrix_size/($num_jobs-1)) * $i;
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351 $self->logger->debug("$start-$end\n", 1);
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352 my $sub_matrix = $matrix->sub_matrix($start, $end);
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353
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354 $sub_matrix->cache_file_name("gene_matrix_synteny$i.ser");
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355 $sub_matrix->dump_path($dump_path);
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356
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357 $sub_matrix->write_to_file;
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358 }
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359 $self->logger->debug("Done.\n", 0, 'stamped');
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360
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361 # create an empty lsf log directory
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362 my $logpath = path_append($self->logger->logpath, 'synteny_rescore');
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363 system("rm -rf $logpath") == 0 or
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364 $self->logger->error("Unable to delete lsf log dir $logpath: $!\n");
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365 system("mkdir -p $logpath") == 0 or
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366 $self->logger->error("Can't create lsf log dir $logpath: $!\n");
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367
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368 # build lsf command
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369 my $lsf_name = 'idmapping_synteny_rescore_'.time;
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370
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371 my $options = $self->conf->create_commandline_options(
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372 logauto => 1,
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373 logautobase => "synteny_rescore",
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374 logpath => $logpath,
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375 interactive => 0,
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376 is_component => 1,
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377 );
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378
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379 my $cmd = qq{$Bin/synteny_rescore.pl $options --index \$LSB_JOBINDEX};
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380
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381 my $bsub_cmd =
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382 sprintf( "|bsub -J%s[1-%d] "
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383 . "-o %s/synteny_rescore.%%I.out "
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384 . "-e %s/synteny_rescore.%%I.err %s",
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385 $lsf_name, $num_jobs, $logpath, $logpath,
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386 $self->conf()->param('lsf_opt_synteny_rescore') );
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387
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388 # run lsf job array
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389 $self->logger->info("Submitting $num_jobs jobs to lsf.\n");
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390 $self->logger->debug("$cmd\n\n");
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391
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392 local *BSUB;
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393 open( BSUB, $bsub_cmd )
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394 or $self->logger->error("Could not open open pipe to bsub: $!\n");
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395
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396 print BSUB $cmd;
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397 $self->logger->error("Error submitting synteny rescoring jobs: $!\n")
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398 unless ($? == 0);
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399 close BSUB;
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400
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401 # submit dependent job to monitor finishing of jobs
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402 $self->logger->info("Waiting for jobs to finish...\n", 0, 'stamped');
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403
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404 my $dependent_job = qq{bsub -K -w "ended($lsf_name)" -q small } .
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405 qq{-o $logpath/synteny_rescore_depend.out /bin/true};
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406
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407 system($dependent_job) == 0 or
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408 $self->logger->error("Error submitting dependent job: $!\n");
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409
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410 $self->logger->info("All jobs finished.\n", 0, 'stamped');
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411
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412 # check for lsf errors
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413 sleep(5);
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414 my $err;
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415 foreach my $i (1..$num_jobs) {
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416 $err++ unless (-e "$logpath/synteny_rescore.$i.success");
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417 }
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418
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419 if ($err) {
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420 $self->logger->error("At least one of your jobs failed.\nPlease check the logfiles at $logpath for errors.\n");
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421 }
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422
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423 # merge and return matrix
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424 $self->logger->debug("Merging rescored matrices...\n");
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425 $matrix->flush;
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426
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427 foreach my $i (1..$num_jobs) {
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428 # read partial matrix created by lsf job from file
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429 my $sub_matrix = Bio::EnsEMBL::IdMapping::ScoredMappingMatrix->new(
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430 -DUMP_PATH => $dump_path,
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431 -CACHE_FILE => "gene_matrix_synteny$i.ser",
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432 );
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433 $sub_matrix->read_from_file;
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434
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435 # merge with main matrix
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436 $matrix->merge($sub_matrix);
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437 }
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438
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439 $self->logger->debug("Done.\n");
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440 $self->logger->debug("Scores after rescoring: ".$matrix->size.".\n");
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441
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442 return $matrix;
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443 }
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444
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445
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446 #
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447 #
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448 =head2 rescore_gene_matrix
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449
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450 Arg[1] : Bio::EnsEMBL::IdMapping::ScoredmappingMatrix $matrix - gene
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451 scores to rescore
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452 Example : my $new_scores = $sf->rescore_gene_matrix($gene_scores);
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453 Description : Rescores a gene matrix. Retains 70% of old score and builds
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454 other 30% from the synteny match.
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455 Return type : Bio::EnsEMBL::IdMapping::ScoredMappingMatrix
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456 Exceptions : thrown on wrong or missing argument
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457 Caller : InternalIdMapper plugins
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458 Status : At Risk
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459 : under development
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460
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|
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461 =cut
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462
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463 sub rescore_gene_matrix {
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464 my $self = shift;
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465 my $matrix = shift;
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466
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467 unless ($matrix and
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468 $matrix->isa('Bio::EnsEMBL::IdMapping::ScoredMappingMatrix')) {
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|
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469 throw('Need a Bio::EnsEMBL::IdMapping::ScoredMappingMatrix.');
|
|
|
470 }
|
|
|
471
|
|
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472 my $retain_factor = 0.7;
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|
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473
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|
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474 foreach my $entry (@{ $matrix->get_all_Entries }) {
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|
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475 my $source_gene = $self->cache->get_by_key('genes_by_id', 'source',
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|
|
476 $entry->source);
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|
|
477
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|
|
478 my $target_gene = $self->cache->get_by_key('genes_by_id', 'target',
|
|
|
479 $entry->target);
|
|
|
480
|
|
|
481 my $highest_score = 0;
|
|
|
482
|
|
|
483 foreach my $sr (@{ $self->get_all_SyntenyRegions }) {
|
|
|
484 my $score = $sr->score_location_relationship($source_gene, $target_gene);
|
|
|
485 $highest_score = $score if ($score > $highest_score);
|
|
|
486 }
|
|
|
487
|
|
|
488 #$self->logger->debug("highscore ".$entry->to_string." ".
|
|
|
489 # sprintf("%.6f\n", $highest_score));
|
|
|
490
|
|
|
491 $matrix->set_score($entry->source, $entry->target,
|
|
|
492 ($entry->score * 0.7 + $highest_score * 0.3));
|
|
|
493 }
|
|
|
494
|
|
|
495 return $matrix;
|
|
|
496 }
|
|
|
497
|
|
|
498
|
|
|
499 =head2 logger
|
|
|
500
|
|
|
501 Arg[1] : (optional) Bio::EnsEMBL::Utils::Logger - the logger to set
|
|
|
502 Example : $object->logger->info("Starting ID mapping.\n");
|
|
|
503 Description : Getter/setter for logger object
|
|
|
504 Return type : Bio::EnsEMBL::Utils::Logger
|
|
|
505 Exceptions : none
|
|
|
506 Caller : constructor
|
|
|
507 Status : At Risk
|
|
|
508 : under development
|
|
|
509
|
|
|
510 =cut
|
|
|
511
|
|
|
512 sub logger {
|
|
|
513 my $self = shift;
|
|
|
514 $self->{'_logger'} = shift if (@_);
|
|
|
515 return $self->{'_logger'};
|
|
|
516 }
|
|
|
517
|
|
|
518
|
|
|
519 =head2 conf
|
|
|
520
|
|
|
521 Arg[1] : (optional) Bio::EnsEMBL::Utils::ConfParser - the configuration
|
|
|
522 to set
|
|
|
523 Example : my $basedir = $object->conf->param('basedir');
|
|
|
524 Description : Getter/setter for configuration object
|
|
|
525 Return type : Bio::EnsEMBL::Utils::ConfParser
|
|
|
526 Exceptions : none
|
|
|
527 Caller : constructor
|
|
|
528 Status : At Risk
|
|
|
529 : under development
|
|
|
530
|
|
|
531 =cut
|
|
|
532
|
|
|
533 sub conf {
|
|
|
534 my $self = shift;
|
|
|
535 $self->{'_conf'} = shift if (@_);
|
|
|
536 return $self->{'_conf'};
|
|
|
537 }
|
|
|
538
|
|
|
539
|
|
|
540 =head2 cache
|
|
|
541
|
|
|
542 Arg[1] : (optional) Bio::EnsEMBL::IdMapping::Cache - the cache to set
|
|
|
543 Example : $object->cache->read_from_file('source');
|
|
|
544 Description : Getter/setter for cache object
|
|
|
545 Return type : Bio::EnsEMBL::IdMapping::Cache
|
|
|
546 Exceptions : none
|
|
|
547 Caller : constructor
|
|
|
548 Status : At Risk
|
|
|
549 : under development
|
|
|
550
|
|
|
551 =cut
|
|
|
552
|
|
|
553 sub cache {
|
|
|
554 my $self = shift;
|
|
|
555 $self->{'_cache'} = shift if (@_);
|
|
|
556 return $self->{'_cache'};
|
|
|
557 }
|
|
|
558
|
|
|
559
|
|
|
560 1;
|
|
|
561
|
