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0
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1 #!/usr/bin/perl -w
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2 #use strict;
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3
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4 %arguments=
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5 (
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6 "AD"=>"T", #value mandatory, T==TRUE F==FALSE
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7 "XL"=>"F", #value mandatory, F==FALSE T==TRUE
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8 "vcf"=>"", #file mandatory, provided at runtime
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9 "disease"=>"", #name optional
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10 "similarD"=>"", #file optional
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11 "lgenes"=>"", #file optional
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12 "leQTL"=>"", #file optional
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13 "keywords"=>"kfile", #file mandatory, but default value
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14 "effects"=>"efile", #file mandatory, but default value
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15 "disease_clinvar"=>8, #numeric mandadory, but default value
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16 "score_AF"=>4, #numeric mandatory, but default value
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17 "score_functional"=>8, #numeric mandatory, but default value
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18 "score_NS"=>6, #numeric mandatory, but default value
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19 "score_nIND"=>8, #numeric mandatory, but default value
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20 "AF"=>0.0001, #numeric mandatory, but default value
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21 "scoreeQTL"=>1, #numeric mandatory, but default value
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22 "nind"=>5, #numeric mandatory, but default value
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23 "scoreG"=>2, #numeric mandatory, but default value
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24 "ifile"=>"", #file optional
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25 "scoreT"=>1, #numeric mandatory, but default value
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26 "scoreGW"=>1, #numeric mandatory but default value
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27 "scoreM"=>1, #numeric mandatory but default value
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28 "scoreR"=>1, #numeric mandatory but default value
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29 "scoreSP"=>1, #numeric mandatory but default value
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30 #####OUTPUT file#############################################
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31 "ofile"=>"final_res.csv", #file #OUTPUT #tabulare
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32 "ovcfile"=>"final_res.vcf",#, #file #OUTOUT #vcf
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33 "osummary"=>"detailed_final_res.csv"
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34 );
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35
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36 @arguments=@ARGV;
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37 for ($i=0;$i<=$#ARGV;$i+=2)
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38 {
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39 $act=$ARGV[$i];
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40 $act=~s/-//g;
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41 $val=$ARGV[$i+1];
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42 if (exists $arguments{$act})
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43 {
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44 $arguments{$act}=$val;
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45 }else{
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46 warn("$act: unknown argument\n");
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47 @valid=keys %arguments;
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48 warn("Valid arguments are @valid\n");
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49 die("All those moments will be lost in time, like tears in rain.\n Time to die!\n");
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50 }
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51 }
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52
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53 $ofile_name=$arguments{"ofile"};
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54 open(O,">$ofile_name");
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55 $ovcfile=$arguments{"ovcfile"};
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56 open(OV,">$ovcfile");
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57 $osummary_name=$arguments{"osummary"};
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58 open(OS,">$osummary_name");
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59 print OS "chr\tstart\tref\talt\tNhom\tNhet\tNind\tGene\tScoreG\tScoreCV\tScoreOth\tScoreAF\tScoreEff\tScoreSP\tScoreTF\tScoremir\tScoreREG\tScoreGWAS\tScoreNS\tScoreQTL\tScoreNi\tScoreT\n";
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60
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61 $ifile=$arguments{"ifile"};
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62 if (-e $ifile)
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63 {
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64 open(IN,$ifile);
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65 while(<IN>)
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66 {
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67 #($G1,$G2)=(split());
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68 #push (@{$interact{$G1}},$G2);
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69 }
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70 }
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71
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72
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73 $file=$arguments{"vcf"} ;
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74 die ("input file $file not found!\n") unless -e $file;
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75
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76 $lgenes=$arguments{"lgenes"};
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77 if (-e $lgenes)
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78 {
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79 open(IN,$lgenes);
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80 while(<IN>)
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81 {
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82 chomp;
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83 $G=(split())[0];
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84 $Lgenes{$G}=1;
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85 }
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86 }
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87
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88
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89 $kfile=$arguments{"keywords"};
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90 die ("keyword file $kfile not found!\n") unless -e $kfile;
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91 open(IN,$kfile);
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92 while(<IN>)
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93 {
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94 chomp;
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95 ($k,$category)=(split())[0,1];
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96 $specialKeys{$k}=$category;
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97 push (@{$annotKeys{$category}},$k);
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98 }
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99
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100 $diseaseO=$arguments{"disease"} ? $arguments{"disease"} : "GinocchioValgoDellaLavandaiaZoppa";
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101 @diseaseO=split(/#/,$diseaseO);
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102
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103 $sfile=$arguments{"similarD"};
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104 if (-e $sfile)
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105 {
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106 open(IN,$sfile);
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107 while(<IN>)
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108 {
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109 chomp;
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110 $Sw=lc($_);
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111 $Sw=~s/\s+//;
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112 push(@kw,$Sw);
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113 }
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114 }
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115
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116 $efile=$arguments{"effects"};
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117 die ("effect file $efile not found!\n") unless -e $efile;
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118 open(IN,$efile);
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119 while(<IN>)
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120 {
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121 chomp;
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122 $effects{$_}=1;
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123 }
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124
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125 $leQTLfile=$arguments{"leQTL"};
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126 if (-e $leQTLfile)
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127 {
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128 open(IN,$leQTLfile);
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129 while(<IN>)
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130 {
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131 chomp();
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132 $Qlist{$_}=1;
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133 }
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134 }
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135
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136 $disease_clinvar=$arguments{"disease_clinvar"};
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137 $score_AF=$arguments{"score_AF"};
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138 $score_functional=$arguments{"score_functional"};
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139 $score_NS=$arguments{"score_NS"};
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140 $score_nIND=$arguments{"score_nIND"};
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141 $score_QTL=$arguments{"scoreeQTL"};
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142 $scoreG=$arguments{"scoreG"};
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143 $scoreM=$arguments{"scoreM"};
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144 $scoreT=$arguments{"scoreT"};
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145 $scoreR=$arguments{"scoreR"};
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146 $scoreGW=$arguments{"scoreGW"};
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147 $scoreSP=$arguments{"scoreSP"};
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148
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149 #print O "CHR\tstart\tgene\tref\talt\tAC\tNhom\tNhet\tNind\tGene\tScoreCV\tScoreOth\tScoreAF\tScoreEff\tScoreNS\tScoreQTL\tScoreNi\tScoreT\n";
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150 print O "CHR\tstart\tgene\tref\talt\tAC\t";
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151
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152 foreach $k (sort keys %specialKeys)
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153 {
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154 print O "$k\t";
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155 }
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156 print O "VINYL_score\n";
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157
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158
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159 open(IN,$file);
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160
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161 #print "$gene_score $disease_HGMD $disease_clinvar $score_functional $score_AF $score_NS $score_eQTL $score_nIND\n";
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162 while(<IN>)
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163 {
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164 if ($_=~/^#/)
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165 {
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166 print OV;
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167 next;
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168 }
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169 chomp();
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170 $summary_line="";
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171 @val=(split(/\t/));
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172 $chr=$val[0];
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173 $start=$val[1];
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174 $pstart=$val[2];
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175 $b1=$val[3];
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176 $b2=$val[4];
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177 $qscore=$val[5];
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178 $pb2=$val[6];
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179 $gene="na";
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180 $annot=$val[7];
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181 $gt=$val[8];
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182 @samples=@val[9..$#val];
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183 $Nhom=0;
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184 $Nhet=0;
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185 $summary_line.="$chr\t$start\t$b1\t$b2\t";
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186 foreach $s (@samples)
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187 {
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188 $sid=(split(/\:/,$s))[0];
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189 next if $sid eq ".";
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190 if ($sid=~/\|/)
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191 {
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192 ($h1,$h2)=(split(/\|/,$sid))[0,1];
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193 }elsif($sid=~/\//){
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194 ($h1,$h2)=(split(/\//,$sid))[0,1];
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195 }
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196 $Nhom++ if $h1==$h2 && $h1 !=0;
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197 $Nhet++ if $h1!=$h2 && ($h1!=0 && $h2!=0) ;
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198 }
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199 $summary_line.="$Nhom\t$Nhet\t";
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200 $samples=(join("\t",@samples));
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201 @terms=(split(/\;/,$annot));
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202 $DIS=0;
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203 if ($_=~/;AC=(\d+);/ || $_=~/\tAC=(\d+);/)
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204 {
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205 $nind=$1;
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206 }
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207 if ($_=~/Gene.refGene=(\w+);/)
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208 {
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209 $gene=$1;
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210 }
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211 $summary_line.="$nind\t$gene\t";
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212 next if $nind==0;
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213 $gene=(split(/\,/,$gene))[0];
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214 $i=0;
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215 %keep=();
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216 $score=0;
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217 %riserva=(7569521=>1, 32974391=>1, 228557681=>1, 228527758=>1, 228525823=>1, 156106964=>1 );
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218 $score+=6 if $riserva{$start};
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219 $G=0;
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220 if ($Lgenes{$gene})
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221 {
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222 $score+=$scoreG;
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223 $G=$scoreG;
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224 }
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225 $summary_line.="$G\t";
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226 foreach $t (@terms)
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227 {
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228 next unless $t;
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229 ($keep,$value)=(split(/\=/,$t))[0,1];
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230 $value="." unless ($value);
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231 $keep{$keep}=$value;
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232 }
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233 if ($keep{"CLNSIG"} ne "."){
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234 $scoreO=0;
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235 $scoreC=0;
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236 $add=0;
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237 $add=$disease_clinvar if ($keep{"CLNSIG"} eq "Pathogenic" || $keep{"CLNSIG"} eq "Pathogenic,_other,_risk_factor" || $keep{"CLNSIG"} eq "pathogenic" || $keep{"CLNSIG"} eq "Pathogenic/Likely_pathogenic" );
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238 $add=$disease_clinvar/2 if ($keep{"CLNSIG"} eq "Likely_pathogenic" || $keep{"CLNSIG"} eq "Conflicting_interpretations_of_pathogenicity" || $keep{"CLNSIG"} eq "likely-pathogenic");
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239 $add-=$disease_clinvar/4 if ($keep{"CLNSIG"} eq "Likely_benign" || $keep{"CLNSIG"} eq "Benign/Likely_benign");
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240 $add-=$disease_clinvar/2 if ($keep{"CLNSIG"} eq "Benign");
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241 @diseases=split(/\|/,$keep{"CLNDN"});
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242 @databases=split(/\|/,$keep{"CLNDISDB"});
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243 for ($i=0;$i<=$#diseases;$i++)
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244 {
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245 $dis=lc $diseases[$i];
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246 $dat=$databases[$i];
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247 $MDO=0;
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248 foreach $disOL (@diseaseO)
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249 {
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250 $disOL=lc $disOL;
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251 if ($dis=~ /$disOL/)
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252 {
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253 if ($dat=~/OMIM/)
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254 {
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255 $scoreO=$add;
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256 }else{
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257 $scoreC=$add;
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258 }
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259 $MDO=1;
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260 last;
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261 }
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262 }
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263 if ($MDO==0)
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264 {
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265 foreach $kv (@kw)
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266 {
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267 if ($dis=~/$kv/)
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268 {
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269 $DIS=1 if $add>0;
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270 if ($dat=~/OMIM/)
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271 {
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272 $scoreO=$add;
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273 }else{
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274 $scoreC=$add;
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275 }
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276 }
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277 }
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278 }
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279 }
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280 $score+=$scoreO+$scoreC;
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281 $summary_line.="$scoreO\t$scoreC\t";
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282 #duplicate this block for KW annotated
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283 }else{
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284 $summary_line.="0\t0\t";
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285 }
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286 @AFkeys=@{$annotKeys{"AF"}};
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287 $AF=0;
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288 foreach $AFK (@AFkeys)
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289 {
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290 $LOC_af=$keep{$AFK} ? $keep{$AFK} : 0 ;
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291 $LOC_af=0 if $LOC_af eq ".";
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292 $AF=$LOC_af if $LOC_af>$AF;
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293 }
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294 $AF=$AF/20 if ($chr eq "chr1" && ($start==228557681 || $start==228527758 || $start==228525823));
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295 if ($AF<=$arguments{"AF"}) #0,00002
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296 {
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297 $score+=$score_AF;
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298 $summary_line.="$score_AF\t";
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299 }elsif($AF>$arguments{"AF"} && $AF<=$arguments{"AF"}*4){
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300 $score+=$score_AF/2;
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301 $summary_line.=$score_AF/2 ."\t";
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302 }elsif($AF>$arguments{"AF"}*4 && $AF<=0.01){
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303 $summary_line.="0\t";
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304 }elsif($AF>0.01){ #commonSNP
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305 $score-=$score_AF/2;
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306 $summary_line.=-$score_AF/2 ."\t";
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307 }
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308
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309 @EFFkeys=@{$annotKeys{"Effect"}};
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310 $EFFS=0;
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311 foreach $EFF (@EFFkeys)
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312 {
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313 $effectO=(split(/\;/,$keep{$EFF}))[0];
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314 $score+=$score_functional if $effects{$effectO};
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315 $EFFS+=$score_functional if $effects{$effectO};
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316 }
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317 $summary_line.="$EFFS\t";
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318
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319 @SPKeys=@{$annotKeys{"Splice"}};
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320 $SPs=0;
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321 foreach $SPk (@SPKeys)
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322 {
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323 next if ($keep{$SPk} eq ".");
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324 if($keep{$SPk}>0.6)
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325 {
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326 $score+=$scoreSP/($#SPKeys+1);
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327 $SPs+=$scoreSP/($#SPKeys+1);
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328 }
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329 }
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330 $summary_line.="$SPs\t";
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331
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332 $TFscore=0;
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333 @TFBSkeys=@{$annotKeys{"tfbs"}};
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334 foreach $T (@TFBSkeys)
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335 {
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336 $score+=$scoreT if $keep{$T} ne ".";
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337 $TFscore+=$scoreT if $keep{$T} ne ".";
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338 }
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339 $summary_line.="$TFscore\t";
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340
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341 $mirscore=0;
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342 @mirkeys=@{$annotKeys{"mirna"}};
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343 foreach $M (@mirkeys)
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344 {
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345 $score+=$scoreM if $keep{$M} ne ".";
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346 $mirscore+=$scoreM if $keep{$M} ne ".";
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347 }
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348 $summary_line.="$mirscore\t";
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349
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350 $REGscore=0;
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351 @REGkeys=@{$annotKeys{"Reg"}};
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352 foreach $R (@REGkeys)
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353 {
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354 $score+=$scoreR if $keep{$R} ne ".";
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355 $REGscore+=$scoreR if $keep{$R} ne ".";
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356 }
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357 $summary_line.="$REGscore\t";
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358
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359 $GWscore=0;
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360 if ($keep{"GWAS"} ne ".")
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361 {
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362 $GW=$keep{"GWAS"};
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363 $GW=lc($GW);
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364 @Gs=(split(/\|/,$GW));
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365 foreach $Gword (@Gs)
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366 {
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367 next if $Gword eq " ";
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368 $Gword=~s/-/ /g;
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369 foreach $kv (@kw)
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370 {
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371 if ($Gword=~/$kv/)
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372 {
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373 $score+=$scoreGW;
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374 $GWscore+=$scoreGW;
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375 last;
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376 }
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377 }
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378 }
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379
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380 }
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381 $summary_line.="$GWscore\t";
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382
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383 $NSa=0;
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384 #print "Exon " . $keep{"ExonicFunc.refGene"}. " $score\n"; #modify here to use kwords in conf file
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385 if ($keep{"ExonicFunc.refGene"} eq "nonsynonymous_SNV")
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386 {
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387 $ND=0;
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388 @NStools=@{$annotKeys{"NStool"}};
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389 foreach $t (@NStools)
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390 {
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391 $NSscore=$keep{$t};
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392 next if $NSscore eq ".";
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393 $NSscore="D" if $t=~/CADD/ && $NSscore>=5;
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394 $ND++ if $NSscore eq "D";
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395 }
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396
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397 if ($ND==$#NStools+1)
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398 {
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399 $score+=$score_NS;
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400 $NSa+=$score_NS;
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401 }elsif($ND>=($#NStools+1)/2){
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402 $score+=$score_NS/(($#NStools+1)/2);
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403 $NSa+=$score_NS/(($#NStools+1)/2);
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404 }elsif($ND==0){
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405 $score+=$score_NS/($#NStools+1); #da commentare. o NS/4
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406 $NSa+=$score_NS/($#NStools+1);
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407 }
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408 }
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409 $summary_line.="$NSa\t";
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410 $iQTL=0;
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411 foreach $QTL (keys %Qlist)
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412 {
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413 next unless $keep{$QTL};
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414 if ($keep{$QTL} ne ".")
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415 {
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416 $score+=$score_QTL;
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417 $iQTL+=$score_QTL; #if ($keep{$QTL} ne ".");
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418 }
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419
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420 }
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421 $summary_line.="$iQTL\t";
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422 if ($nind>=$arguments{"nind"} && $AF<=0.01)
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423 {
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424 $score+=$score_nIND;
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425 $summary_line.="$score_nIND\t";
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426 }elsif($nind>=$arguments{"nind"}/2 && $nind<$arguments{"nind"} && $AF<=0.01){
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427 $score+=$score_nIND/2;
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428 $summary_line.=$score_nIND/2 ."\t";
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429 }else{
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430 $summary_line.="0\t";
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431 }
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432 chomp();
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433 chop($_);
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434 $outL="";
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435 $IS_MAL=0;
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436 foreach $k (sort keys %specialKeys)
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437 {
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438 unless($keep{$k})
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439 {
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440 #warn("Malformed $_\n");
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441 warn("please check $k is missing\n");
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442 $IS_MAL=1;
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443 }
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444 $outL.="$keep{$k}\t";
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445 }
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446 next if $IS_MAL==1;
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|
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447 $score=$score/2 if $arguments{"AD"} eq "F" && $Nhom==0;
|
|
|
448 $score=$score/2 if $arguments{"XL"} eq "T" && $chr ne "chrX";
|
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|
449 $summary_line.="$score\n";
|
|
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450 print O "$chr\t$start\t$gene\t$b1\t$b2\t$nind\t$outL$score\n"; #if $score>=12 || $DIS==1;
|
|
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451 print OV "$chr\t$start\t$pstart\t$b1\t$b2\t$qscore\t$pb2\t$annot;VINYL_score=$score\t$gt\t$samples\n";
|
|
|
452 print OS "$summary_line";
|
|
|
453 }
|
