--- /dev/null	Thu Jan 01 00:00:00 1970 +0000
+++ b/old_version/score_complete_alt.pl	Wed Jul 22 19:20:30 2020 +0000
@@ -0,0 +1,296 @@
+#!/usr/bin/perl  -w
+#use strict;
+
+%arguments=
+(
+"vcf"=>"",		#file	mandatory, provided at runtime
+"disease"=>"",		#name	optional
+"similarD"=>"",         #file optional
+"lgenes"=>"",           #file optional
+"leQTL"=>"qfile",       #file   mandatory, but default value
+"keywords"=>"kfile",	#file	mandatory, but default value
+"effects"=>"efile",	#file	mandatory, but default value
+"disease_clinvar"=>8, 	#numeric mandadory, but default value
+"score_AF"=>4, 		#numeric mandatory, but default value
+"score_functional"=>8,  #numeric mandatory, but default value
+"score_NS"=>6,		#numeric mandatory, but default value
+"score_nIND"=>8,	#numeric mandatory, but default value
+"AF"=>0.0001,		#numeric mandatory, but default value
+"scoreeQTL"=>1,		#numeric mandatory, but default value
+"nind"=>5,		#numeric  mandatory, but default value
+"scoreG"=>2,		#numeric  mandatory, but default value
+#####OUTPUT file#############################################
+"ofile"=>"final_res.csv", #file #OUTPUT #tabulare
+"ovcfile"=>"final_res.vcf"  #file #OUTOUT #vcf
+);
+
+
+@arguments=@ARGV;
+for ($i=0;$i<=$#ARGV;$i+=2)
+{
+	$act=$ARGV[$i];
+	$act=~s/-//g;
+	$val=$ARGV[$i+1];
+	if (exists $arguments{$act})
+	{
+		$arguments{$act}=$val;
+	}else{
+		warn("$act: unknown argument\n");
+		@valid=keys %arguments;
+		warn("Valid arguments are @valid\n");
+		die("All those moments will be lost in time, like tears in rain.\n Time to die!\n");
+	}
+	#print "$act $val\n";
+}
+
+$ofile_name=$arguments{"ofile"};
+open(O,">$ofile_name");
+$ovcfile=$arguments{"ovcfile"};
+open(OV,">$ovcfile");
+
+
+$file=$arguments{"vcf"} ;
+die ("input file $file not found!\n") unless -e $file;
+
+$lgenes=$arguments{"lgenes"};
+if (-e $lgenes)
+{
+	open(IN,$lgenes);
+	while(<IN>)
+	{
+		chomp;
+		$Lgenes{$_}=1;
+	}
+}
+
+
+$kfile=$arguments{"keywords"};
+die ("keyword file $kfile not found!\n") unless -e $kfile;
+open(IN,$kfile);
+while(<IN>)
+{
+	chomp;
+	$specialKeys{$_}=1;	
+}
+
+
+$diseaseO=$arguments{"disease"} ? $arguments{"disease"} : "GinocchioValgoDellaLavandaiaZoppa";
+
+$sfile=$arguments{"similarD"};
+if (-e $sfile)
+{
+	open(IN,$sfile);
+	while(<IN>)
+	{
+		chomp;
+		push(@kw,$_)
+	}
+}
+
+$efile=$arguments{"effects"};
+die ("effect file $efile not found!\n") unless -e $efile;
+open(IN,$efile);
+while(<IN>)
+{
+        chomp;
+        $effects{$_}=1;
+}
+
+$leQTLfile=$arguments{"leQTL"};
+if (-e $leQTLfile)
+{	
+	open(IN,$leQTLfile);
+        while(<IN>)
+	{
+		chomp();
+		$Qlist{$_}=1;
+	}
+}
+
+$disease_clinvar=$arguments{"disease_clinvar"};
+$score_AF=$arguments{"score_AF"};
+$score_functional=$arguments{"score_functional"};
+$score_NS=$arguments{"score_NS"};
+$score_nIND=$arguments{"score_nIND"};
+$score_QTL=$arguments{"scoreeQTL"};
+$scoreG=$arguments{"scoreG"};
+
+print O "CHR\tstart\tgene\tref\talt\tAC\t";
+foreach $k (sort keys %specialKeys)
+{
+	print O "$k\t";
+}
+print O "Score\n";
+
+%damaged=();
+open(IN,$file);
+
+#print "$gene_score $disease_HGMD $disease_clinvar $score_functional $score_AF $score_NS $score_eQTL $score_nIND\n";
+while(<IN>)
+{
+	if ($_=~/^#/)
+	{
+		print OV;
+		next;
+	}
+	chomp();
+	@val=(split(/\t/));
+	$chr=$val[0];
+	$start=$val[1];
+	$pstart=$val[2];
+	$b1=$val[3];
+	$b2=$val[4];
+	$qscore=$val[5];
+	$pb2=$val[6];
+	$gene="na";
+	$annot=$val[7];
+	$gt=$val[8];
+	@samples=@val[9..$#val];
+	$samples=(join("\t",@samples));
+	@terms=(split(/\;/,$annot));
+	$DIS=0;
+	if ($_=~/;AC=(\d+);/)
+	{
+		$nind=$1;
+	}
+	if ($_=~/Gene.refGene=(\w+);/)
+	{
+		$gene=$1;
+	}
+	next if $nind==0;
+	$gene=(split(/\,/,$gene))[0];
+	$i=0;
+	%keep=();
+	$score=0;
+	$score+=$scoreG if $Lgenes{$gene};
+	foreach $t (@terms)
+	{
+		($keep,$value)=(split(/\=/,$t))[0,1];
+		$keep{$keep}=$value;
+	}
+	
+	if ($keep{"CLNSIG"} ne "."){
+		$scoreO=0;
+        	$scoreC=0;
+		$add=0;
+		$add=$disease_clinvar  if ($keep{"CLNSIG"} eq "Pathogenic" || $keep{"CLNSIG"} eq "Pathogenic,_other,_risk_factor" || $keep{"CLNSIG"} eq "pathogenic" || $keep{"CLNSIG"} eq "Pathogenic/Likely_pathogenic" );
+		$add=$disease_clinvar/2  if ($keep{"CLNSIG"} eq "Likely_pathogenic" || $keep{"CLNSIG"} eq "Conflicting_interpretations_of_pathogenicity" || $keep{"CLNSIG"} eq "likely-pathogenic");
+		$add=-$disease_clinvar/2 if ($keep{"CLNSIG"} eq "Likely_benign"	||  $keep{"CLNSIG"} eq "Benign/Likely_benign");
+		$add=-$disease_clinvar if ($keep{"CLNSIG"} eq "Benign");
+		@diseases=split(/\|/,$keep{"CLNDN"});
+                @databases=split(/\|/,$keep{"CLNDISDB"});
+                for ($i=0;$i<=$#diseases;$i++)
+                {
+			$dis=lc $diseases[$i];
+			$dat=$databases[$i];
+			if ($dis=~ /$diseaseO/)
+                       	{
+                        	if ($dat=~/OMIM/)
+                                {	
+					$scoreO=$add;
+                                }else{
+					$scoreC=$add;
+                                }
+				last;
+                        }else{
+                        	foreach $kv (@kw)
+                                {
+					if ($dis=~/$kv/)
+					{
+						$DIS=1 if $add>0;
+						if ($dat=~/OMIM/)
+                                        	{
+							$scoreO=$add;
+                                        	}else{
+							$scoreC=$add;
+                                        	}
+					}
+                                 }
+                        }
+		}
+		$score+=$scoreO+$scoreC;	
+	}
+	$esp=$keep{"esp6500siv2_ea"} eq "." ? 0 : $keep{"esp6500siv2_ea"};
+	$g1000=$keep{"1000g2015aug_all"} eq "." ? 0 : $keep{"1000g2015aug_all"} ;
+	$exac=$keep{"ExAC_NFE"} eq "." ? 0 : $keep{"ExAC_NFE"};
+	$gnomad=$keep{"gnomAD_exome_NFE"} eq "." ? 0 : $keep{"gnomAD_exome_NFE"};
+	@AF=($esp,$g1000,$exac,$gnomad);
+	@AF=sort{$a<=>$b} @AF;
+	$AF=$AF[-1];
+	# Variante molto rara 0.0001 2 punti
+	# Variante rara 0.004 1 punto
+	if ($AF<=$arguments{"AF"}) #0,00002
+	{
+		$score+=$score_AF;
+	}elsif($AF>$arguments{"AF"} && $AF<=$arguments{"AF"}*4){
+		$score+=$score_AF/2;
+	}elsif($AF>0.01){	#commonSNP
+		$score-=$score_AF/2;
+	}
+	
+	$effectO=(split(/\;/,$keep{"ExonicFunc.refGene"}))[0];
+	if ($effects{$effectO})
+	{
+		 $damaged{$gene}{"D"}++;
+		 $score+=$score_functional;
+	}
+	#print "Exon " . $keep{"ExonicFunc.refGene"}. " $score\n";
+	if ($keep{"ExonicFunc.refGene"} eq "nonsynonymous_SNV"){
+		
+		if ($keep{"MetaSVM_pred"} eq "D" && $keep{"CADD_raw"}>=5)
+		{
+			$score+=$score_NS;
+			$damaged{$gene}{"D"}++;
+		}elsif($keep{"MetaSVM_pred"} eq "D" && $keep{"CADD_raw"}<5){
+			$score+=$score_NS/2;
+		}elsif($keep{"MetaSVM_pred"} ne "D" && $keep{"CADD_raw"}>=5){
+                        $score+=$score_NS/2;
+                }
+	}
+	#print "NS ". $keep{"ExonicFunc.refGene"} . " $score\n";
+	$damaged{$gene}{"tot"}++;
+	if ($keep{"Func.refGene"} eq "splicing"){
+		$score+=$score_functional;
+	}
+	#print "SPL ". $keep{"Func.refGene"} . " $score\n";
+	foreach $QTL  (keys %Qlist)
+	{
+		next unless $keep{$QTL};
+		$score+=$score_QTL if ($keep{$QTL} ne ".");
+	}
+	if ($nind>=$arguments{"nind"} && $AF<=0.01)
+	{
+		$score+=$score_nIND;
+	}elsif($nind>=$arguments{"nind"}/2 && $nind<$arguments{"nind"} && $AF<=0.01){
+		$score+=$score_nIND/2;
+	}
+	chomp();
+	#$scores{$score}++;
+	chop($_);
+	$outL="";
+	foreach $k (sort keys %specialKeys)
+	{
+		 #die("$k\n") unless $keep{$k};
+		$outL.="$keep{$k}\t";
+	}
+	print O "$chr\t$start\t$gene\t$b1\t$b2\t$nind\t$outL$score\n"; #if $score>=12 || $DIS==1;
+	print OV "$chr\t$start\t$pstart\t$b1\t$b2\t$qscore\t$pb2\t$annot;COSO_score=$score\t$gt\t$samples\n";
+}
+#open(O,">$file.gc.list.csv");
+#foreach $gene (sort{$a<=>$b} keys %G)
+#{	
+#	$pos=$G{$gene}{"GR"} ? $G{$gene}{"GR"} : 0;
+#	$neg=$G{$gene}{"LW"} ? $G{$gene}{"LW"} : 0;
+	#print O "$gene $pos $neg\n";
+	##$Tscore+=$scores{$score} if $score>=$coff;
+#}
+
+#open(D,">$file\_damaged.csv");
+#foreach $gene (sort{$a<=>$b} keys %damaged)
+#{
+#	$D=$damaged{$gene}{"D"} ? $damaged{$gene}{"D"} : 0;
+#	$T=$damaged{$gene}{"tot"};
+	#print D "$gene $D $T\n";
+#}
+
+#print "$Tscore\n";