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1 =head1 LICENSE
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2
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3 Copyright [1999-2015] Wellcome Trust Sanger Institute and the EMBL-European Bioinformatics Institute
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4 Copyright [2016-2018] EMBL-European Bioinformatics Institute
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5
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6 Licensed under the Apache License, Version 2.0 (the "License");
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7 you may not use this file except in compliance with the License.
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8 You may obtain a copy of the License at
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9
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10 http://www.apache.org/licenses/LICENSE-2.0
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11
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12 Unless required by applicable law or agreed to in writing, software
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13 distributed under the License is distributed on an "AS IS" BASIS,
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14 WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
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15 See the License for the specific language governing permissions and
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16 limitations under the License.
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17
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18 =head1 CONTACT
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19
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20 Ensembl <http://www.ensembl.org/info/about/contact/index.html>
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21
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22 =cut
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23
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24 =head1 NAME
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25
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26 FATHMM
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27
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28 =head1 SYNOPSIS
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29
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30 mv FATHMM.pm ~/.vep/Plugins
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31 ./vep -i variations.vcf --plugin FATHMM,"python /path/to/fathmm/fathmm.py"
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32
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33 =head1 DESCRIPTION
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34
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35 A VEP plugin that gets FATHMM scores and predictions for missense variants.
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36
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37 You will need the fathmm.py script and its dependencies (Python, Python
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38 MySQLdb). You should create a "config.ini" file in the same directory as the
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39 fathmm.py script with the database connection options. More information about
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40 how to set up FATHMM can be found on the FATHMM website at
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41 https://github.com/HAShihab/fathmm.
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42
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43 A typical installation could consist of:
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44
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45 > wget https://raw.github.com/HAShihab/fathmm/master/cgi-bin/fathmm.py
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46 > wget ftp://supfam2.cs.bris.ac.uk/FATHMM/database/fathmm.v2.1.SQL
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47 > mysql -h[host] -P[port] -u[user] -p[pass] -e"CREATE DATABASE fathmm"
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48 > mysql -h[host] -P[port] -u[user] -p[pass] -Dfathmm < fathmm.v2.1.SQL
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49 > echo "[DATABASE]\nHOST = [host]\nPORT = [port]\nUSER = [user]\nPASSWD = [pass]\nDB = fathmm\n" > config.ini
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50
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51 =cut
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52
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53 package FATHMM;
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54
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55 use strict;
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56 use warnings;
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57
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58 use Bio::EnsEMBL::Variation::Utils::BaseVepPlugin;
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59
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60 use base qw(Bio::EnsEMBL::Variation::Utils::BaseVepPlugin);
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61
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62 sub new {
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63 my $class = shift;
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64
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65 my $self = $class->SUPER::new(@_);
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66
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67 # get command
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68 my $command = $self->params->[0];
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69
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70 die 'ERROR: No FATHMM command specified. Specify path to FATHMM with e.g. --plugin FATHMM,"python /path/to/fathmm/fathmm.py"\n' unless defined($command);
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71
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72 die 'ERROR: Your FATHMM command does not look correct; it should looks something like "python /path/to/fathmm/fathmm.py"\n' unless $command =~ /python.+fathmm\.py/;
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73
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74 $self->{command} = $command;
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75
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76 die 'ERROR: Temporary directory '.$self->{config}->{tmpdir}.' not found - specify an existing directory with --tmpdir [dir]\n' unless -d $self->{config}->{tmpdir};
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77
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78 return $self;
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79 }
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80
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81 sub version {
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82 return 71;
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83 }
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84
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85 sub feature_types {
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86 return ['Transcript'];
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87 }
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88
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89 sub get_header_info {
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90 return {
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91 FATHMM => "FATHMM prediction (score)",
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92 };
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93 }
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94
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95 sub run {
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96 my ($self, $tva) = @_;
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97
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98 # only for missense variants
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99 return {} unless grep {$_->SO_term eq 'missense_variant'} @{$tva->get_all_OverlapConsequences};
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100
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101 # configure command
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102 my $command = $self->{command};
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103 $command =~ m/(\s.+)\/.+/;
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104 my $command_dir = $1;
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105
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106 # configure tmp dir and in/out files for FATHMM
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107 my $tmp_dir = $self->{config}->{tmpdir};
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108 my $tmp_in_file = $tmp_dir."/fathmm_$$\.in";
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109 my $tmp_out_file = $tmp_dir."/fatmm_$$\.out";
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110
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111 # get required input data from TVA
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112 my $protein = $tva->transcript->{_protein} || $tva->transcript->translation->stable_id;
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113 my $aa_change = $tva->pep_allele_string;
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114 my $aa_pos = $tva->transcript_variation->translation_start;
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115 $aa_change =~ s/\//$aa_pos/;
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116
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117 # check we have valid strings
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118 return {} unless $protein && $aa_change =~ /^[A-Z]\d+[A-Z]$/;
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119
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120 # write input file
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121 open IN, ">$tmp_in_file" or die "ERROR: Could not write to file $tmp_in_file\n";
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122 print IN "$protein $aa_change\n";
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123 close IN;
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124
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125 # run command
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126 my $fathmm_err = `cd $command_dir; $command $tmp_in_file $tmp_out_file;`;
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127
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128 # read output file
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129 open OUT, $tmp_out_file or die "ERROR: Could not read from file $tmp_out_file\n";
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130
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131 my ($pred, $score);
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132 while(<OUT>) {
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133 next if /^\#/;
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134 chomp;
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135 my @data = split;
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136 ($pred, $score) = ($data[4], $data[5]);
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137 }
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138 close OUT;
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139
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140 # delete temporary files
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141 unlink($tmp_in_file, $tmp_out_file);
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142
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143 return $pred && $score ? {
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144 FATHMM => "$pred($score)",
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145 } : {};
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146 }
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147
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148 1;
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149
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