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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::Variation::BaseVariationFeatureOverlap
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24
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25 =head1 SYNOPSIS
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26
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27 use Bio::EnsEMBL::Variation::BaseVariationFeatureOverlap;
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28
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29 my $bvfo = Bio::EnsEMBL::Variation::BaseVariationFeatureOverlap->new(
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30 -feature => $feature,
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31 -base_variation_feature => $var_feat
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32 );
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33
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34 print "consequence type: ", (join ",", @{ $bvfo->consequence_type }), "\n";
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35 print "most severe consequence: ", $bvfo->display_consequence, "\n";
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36
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37 =head1 DESCRIPTION
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38
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39 A BaseVariationFeatureOverlap represents a BaseVariationFeature which is in close
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40 proximity to another Ensembl Feature. It is the superclass of variation feature
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41 specific classes such as VariationFeatureOverlap and StructuralVariationOverlap
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42 and has methods common to all such objects. You will not normally instantiate this
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43 class directly, instead instantiating one of the more specific subclasses.
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44
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45 =cut
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46
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47 package Bio::EnsEMBL::Variation::BaseVariationFeatureOverlap;
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48
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49 use strict;
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50 use warnings;
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51
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52 use Bio::EnsEMBL::Utils::Argument qw(rearrange);
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53 use Bio::EnsEMBL::Utils::Scalar qw(assert_ref);
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54 use Bio::EnsEMBL::Utils::Exception qw(throw warning);
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55 use Bio::EnsEMBL::Variation::Utils::VariationEffect qw(overlap within_cds);
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56
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57 sub new {
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58 my $class = shift;
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59
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60 my (
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61 $adaptor,
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62 $base_variation_feature,
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63 $feature,
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64 $no_transfer
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65 ) = rearrange([qw(
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66 ADAPTOR
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67 BASE_VARIATION_FEATURE
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68 FEATURE
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69 NO_TRANSFER
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70 )], @_);
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71
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72 assert_ref($base_variation_feature, 'Bio::EnsEMBL::Variation::BaseVariationFeature');
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73
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74 if (defined $feature) {
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75
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76 assert_ref($feature, 'Bio::EnsEMBL::Feature');
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77
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78 # we need to ensure the Feature and the BaseVariationFeature live on the same slice
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79 # so we explicitly transfer the Feature here
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80 unless($no_transfer && $no_transfer == 1) {
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81 $feature = $feature->transfer($base_variation_feature->slice)
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82 or throw("Unable to transfer the supplied feature to the same slice as the base variation feature");
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83 }
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84 }
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85
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86 my $self = bless {
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87 base_variation_feature => $base_variation_feature,
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88 feature => $feature,
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89 adaptor => $adaptor,
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90 }, $class;
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91
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92 return $self;
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93 }
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94
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95 sub new_fast {
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96 my ($class, $hashref) = @_;
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97 return bless $hashref, $class;
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98 }
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99
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100 =head2 feature
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101
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102 Arg [1] : (optional) A Bio::EnsEMBL::Feature
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103 Description: Get/set the associated Feature, lazy-loading it if required
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104 Returntype : Bio::EnsEMBL::Feature
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105 Exceptions : throws isf the argument is the wrong type
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106 Status : At Risk
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107
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108 =cut
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109
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110 sub feature {
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111 my ($self, $feature, $type) = @_;
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112
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113 if ($feature) {
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114 assert_ref($feature, 'Bio::EnsEMBL::Feature');
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115 $self->{feature} = $feature;
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116 }
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117
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118 if ($type && !$self->{feature}) {
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119
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120 # try to lazy load the feature
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121
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122 if (my $adap = $self->{adaptor}) {
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123
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124 my $get_method = 'get_'.$type.'Adaptor';
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125
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126 # XXX: this can doesn't work because the method is AUTOLOADed, need to rethink this...
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127 #if ($adap->db->dnadb->can($get_method)) {
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128 if (my $fa = $adap->db->dnadb->$get_method) {
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129
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130 # if we have a stable id for the feature use that
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131 if (my $feature_stable_id = $self->{_feature_stable_id}) {
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132 if (my $f = $fa->fetch_by_stable_id($feature_stable_id)) {
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133 $self->{feature} = $f;
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134 delete $self->{_feature_stable_id};
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135 }
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136 }
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137 elsif (my $feature_label = $self->{_feature_label}) {
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138 # get a slice covering the vf
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139
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140 #for my $f ($fa->fetch_all_by_Slice_constraint)
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141 }
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142 }
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143 #}
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144 else {
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145 warn "Cannot get an adaptor for type: $type";
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146 }
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147 }
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148 }
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149
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150 return $self->{feature};
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151 }
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152
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153 sub _fetch_feature_for_stable_id {
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154
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155 # we shouldn't actually need this method as there will apparently
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156 # soon be core support for fetching any feature by its stable id,
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157 # but I'm waiting for core to add this...
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158
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159 my ($self, $feature_stable_id) = @_;
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160
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161 my $type_lookup = {
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162 G => { type => 'Gene', group => 'core' },
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163 T => { type => 'Transcript', group => 'core' },
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164 R => { type => 'RegulatoryFeature', group => 'funcgen' },
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165 };
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166
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167 if ($feature_stable_id =~ /^ENS[A-Z]*([G|R|T])\d+$/) {
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168
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169 my $type = $type_lookup->{$1}->{type};
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170 my $group = $type_lookup->{$1}->{group};
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171
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172 if (my $adap = $self->{adaptor}) {
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173
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174 my $get_method = 'get_'.$type.'Adaptor';
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175
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176 if ($adap->db->dnadb->can($get_method)) {
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177 if (my $fa = $adap->db->dnadb->$get_method) {
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178
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179 # if we have a stable id for the feature use that
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180 if (my $feature_stable_id = $self->{_feature_stable_id}) {
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181 if (my $f = $fa->fetch_by_stable_id($feature_stable_id)) {
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182 $self->{feature} = $f;
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183 delete $self->{_feature_stable_id};
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184 }
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185 }
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186 elsif (my $feature_label = $self->{_feature_label}) {
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187 # get a slice covering the vf
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188
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189
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190 #for my $f ($fa->fetch_all_by_Slice_constraint)
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191 }
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192 }
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193 }
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194 else {
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195 warn "Cannot get an adaptor for type: $type";
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196 }
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197 }
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198 }
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199 }
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200
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201 sub _fetch_adaptor_for_group {
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202 my ($self, $group) = @_;
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203
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204 }
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205
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206 sub _feature_stable_id {
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207 my $self = shift;
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208 if ($self->feature && $self->feature->can('stable_id')) {
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209 return $self->feature->stable_id;
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210 }
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211 elsif (my $id = $self->{_feature_stable_id}) {
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212 return $id;
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213 }
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214 else {
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215 return undef;
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216 }
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217 }
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218
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219 =head2 base_variation_feature
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220
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221 Arg [1] : (optional) A Bio::EnsEMBL::Variation::BaseVariationFeature
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222 Description: Get/set the associated BaseVariationFeature
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223 Returntype : Bio::EnsEMBL::Variation::BaseVariationFeature
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224 Exceptions : throws if the argument is the wrong type
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225 Status : At Risk
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226
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227 =cut
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228
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229 sub base_variation_feature {
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230 my ($self, $bvf) = @_;
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231
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232 if ($bvf) {
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233 assert_ref($bvf, 'Bio::EnsEMBL::Variation::BaseVariationFeature');
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234 $self->{base_variation_feature} = $bvf;
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235 }
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236
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237 return $self->{base_variation_feature};
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238 }
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239
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240 =head2 add_BaseVariationFeatureOverlapAllele
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241
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242 Arg [1] : A Bio::EnsEMBL::Variation::BaseVariationFeatureOverlapAllele instance
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243 Description: Add an allele to this BaseVariationFeatureOverlap
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244 Returntype : none
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245 Exceptions : throws if the argument is not the expected type
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246 Status : At Risk
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247
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248 =cut
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249
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250 sub add_BaseVariationFeatureOverlapAllele {
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251 my ($self, $bvfoa) = @_;
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252
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253 assert_ref($bvfoa, 'Bio::EnsEMBL::Variation::BaseVariationFeatureOverlapAllele');
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254
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255 if ($bvfoa->is_reference) {
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256 $self->{reference_allele} = $bvfoa;
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257 }
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258 else {
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259 my $alt_alleles = $self->{alt_alleles} ||= [];
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260 push @$alt_alleles, $bvfoa;
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261 }
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262 }
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263
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264 =head2 get_reference_BaseVariationFeatureOverlapAllele
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265
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266 Description: Get the object representing the reference allele of this BaseVariationFeatureOverlapAllele
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267 Returntype : Bio::EnsEMBL::Variation::BaseVariationFeatureOverlapAllele instance
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268 Exceptions : none
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269 Status : At Risk
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270
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271 =cut
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272
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273 sub get_reference_BaseVariationFeatureOverlapAllele {
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274 my $self = shift;
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275 return $self->{reference_allele};
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276 }
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277
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278 =head2 get_all_alternate_BaseVariationFeatureOverlapAlleles
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279
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280 Description: Get a list of the alternate alleles of this BaseVariationFeatureOverlapAllele
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281 Returntype : listref of Bio::EnsEMBL::Variation::BaseVariationFeatureOverlapAllele objects
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282 Exceptions : none
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283 Status : At Risk
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284
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285 =cut
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286
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287 sub get_all_alternate_BaseVariationFeatureOverlapAlleles {
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288 my $self = shift;
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289
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290 $self->{alt_alleles} ||= [];
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291
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292 return $self->{alt_alleles};
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293 }
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294
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295 =head2 get_all_BaseVariationFeatureOverlapAlleles
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296
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297 Description: Get a list of the all the alleles, both reference and alternate, of this
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298 BaseVariationFeatureOverlap
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299 Returntype : listref of Bio::EnsEMBL::Variation::BaseVariationFeatureOverlapAllele objects
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300 Exceptions : none
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301 Status : At Risk
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302
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303 =cut
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304
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305 sub get_all_BaseVariationFeatureOverlapAlleles {
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306 my $self = shift;
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307
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308 my @alleles = @{ $self->get_all_alternate_BaseVariationFeatureOverlapAlleles };
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309
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310 my $ref = $self->get_reference_BaseVariationFeatureOverlapAllele;
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311
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312 unshift @alleles, $ref if defined $ref;
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313
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314 return \@alleles;
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315 }
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316
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317 =head2 consequence_type
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318
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319 Arg [1] : (optional) String $term_type
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320 Description: Get a list of all the unique consequence terms of the alleles of this
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321 BaseVariationFeatureOverlap. By default returns Ensembl display terms
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322 (e.g. 'NON_SYNONYMOUS_CODING'). $term_type can also be 'label'
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323 (e.g. 'Non-synonymous coding'), 'SO' (Sequence Ontology, e.g.
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324 'non_synonymous_codon') or 'NCBI' (e.g. 'missense')
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325 Returntype : listref of strings
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326 Exceptions : none
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327 Status : At Risk
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328
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329 =cut
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330
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331 sub consequence_type {
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332 my $self = shift;
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333 my $term_type = shift;
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334
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335 my $method_name;
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336
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337 # delete cached term
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338 if(defined($term_type)) {
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339 delete $self->{_consequence_type};
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340 $method_name = $term_type.($term_type eq 'label' ? '' : '_term');
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341 $method_name = 'SO_term' unless defined $self->most_severe_OverlapConsequence && $self->most_severe_OverlapConsequence->can($method_name);
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342 }
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343
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344 $method_name ||= 'SO_term';
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345
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346 unless ($self->{_consequence_type}) {
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347
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348 # use a hash to ensure we don't include redundant terms (because more than one
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349 # allele may have the same consequence SO_term)
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350
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351 my %cons_types;
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352
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353 for my $allele (@{ $self->get_all_alternate_BaseVariationFeatureOverlapAlleles }) {
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354 for my $cons (@{ $allele->get_all_OverlapConsequences }) {
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355 $cons_types{$cons->$method_name} = $cons->rank;
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356 }
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357 }
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358
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359 # sort the consequence types by rank such that the more severe terms are earlier in the list
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360
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361 $self->{_consequence_type} = [ sort { $cons_types{$a} <=> $cons_types{$b} } keys %cons_types ];
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362 }
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363
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364 return $self->{_consequence_type};
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365 }
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366
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367 =head2 most_severe_OverlapConsequence
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368
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369 Description: Get the OverlapConsequence considered (by Ensembl) to be the most severe
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370 consequence of all the alleles of this VariationFeatureOverlap
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371 Returntype : Bio::EnsEMBL::Variation::OverlapConsequence
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372 Exceptions : none
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373 Status : At Risk
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374
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375 =cut
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376
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377 sub most_severe_OverlapConsequence {
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378 my $self = shift;
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379
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380 unless ($self->{_most_severe_consequence}) {
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381
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382 my $highest;
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383
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384 for my $allele (@{ $self->get_all_alternate_BaseVariationFeatureOverlapAlleles }) {
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385 for my $cons (@{ $allele->get_all_OverlapConsequences }) {
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386 $highest ||= $cons;
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387 if ($cons->rank < $highest->rank) {
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388 $highest = $cons;
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389 }
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390 }
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391 }
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392
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393 $self->{_most_severe_consequence} = $highest;
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394 }
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395
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396 return $self->{_most_severe_consequence};
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397 }
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398
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399 =head2 display_consequence
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400
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401 Arg [1] : (optional) String $term_type
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402 Description: Get the term for the most severe OverlapConsequence of this
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403 VariationFeatureOverlap. By default returns Ensembl display terms
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404 (e.g. 'NON_SYNONYMOUS_CODING'). $term_type can also be 'label'
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405 (e.g. 'Non-synonymous coding'), 'SO' (Sequence Ontology, e.g.
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406 'non_synonymous_codon') or 'NCBI' (e.g. 'missense')
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407 Returntype : string
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408 Exceptions : none
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409 Status : At Risk
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410
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411 =cut
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412
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413 sub display_consequence {
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414 my $self = shift;
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415 my $term_type = shift;
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416
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417 my $method_name;
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418
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419 # delete cached term
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420 if(defined($term_type)) {
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421 $method_name = $term_type.($term_type eq 'label' ? '' : '_term');
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422 $method_name = 'SO_term' unless @{$self->get_all_OverlapConsequences} && $self->get_all_OverlapConsequences->[0]->can($method_name);
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423 }
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424
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425 $method_name ||= 'SO_term';
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426
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427 my $worst_conseq = $self->most_severe_OverlapConsequence;
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428
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429 return $worst_conseq ? $worst_conseq->$method_name : '';
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430 }
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431
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432 sub adaptor {
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433 my $self = shift;
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434 $self->{adaptor} = shift if @_;
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435
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436 # make adaptor an anonymous hash in its absence
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437 # this allows the VEP to cache OverlapConsequences in offline mode
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438 $self->{adaptor} ||= {};
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439
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440 return $self->{adaptor};
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441 }
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442
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443 1;
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444
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