#!/usr/bin/perl
use strict;
use warnings;

my ($codes_dir,$name,$output_dir,$project)=@ARGV;
die "useage:perl $0 codes_dir name output_dir project cancer_type" unless @ARGV==5;



open INFO,"$codes_dir/info.txt";
<INFO>;
my (@fusion,@longindel);
my $cancer_type=$ARGV[4];
while (<INFO>){
    chomp;
    my @line=split(/\t/,$_);
    if ($line[0] eq $project){
        if($line[6] ne "NA"){
			@fusion=split(/\//,$line[6]);
		}
		if($line[7] ne "NA"){
			@longindel=split(/\//,$line[7]);
		}	
	}	
}
open THERAPY,"/dataseq/jmdna/codes/reportbase/targetTherapy.txt";
my $h1=<THERAPY>;
chomp $h1;
my %therapy;
while(<THERAPY>){
	chomp;
	my @line=split("\t");
	push @{$therapy{$line[0]}{$line[1]}},$_ if ($line[1]=~/fusion/i and $line[9] ne 'D' and $line[5] ne 'CSCO' and $line[2] !~/Leukemia|Lymphoma|Myeloid/i);
}

##药物翻译信息
open DRUG,"/dataseq/jmdna/codes/reportbase/target_drug.txt";
my %drug;
<DRUG>;
while(<DRUG>){
	chomp;
	my @line=split(/\t/);
	next unless $line[1];
	foreach my $drug(split(/\|/,$line[0])){		
		$drug{lc$drug}=$line[1];
	}
}

sub drug{
	my $drugs=shift @_;
	my @translation;
	foreach my $drug(split(/,/,$drugs)){
		if ($drug=~/\+/){
			my $plus;
			foreach my $drug_c(split(/\s+\+\s+/,$drug)){
				my $new=(exists $drug{lc$drug_c})?$drug{lc$drug_c}:($drug_c);
				$plus.=" + $new";
			}
			$plus=~s/^ \+ //;
			push @translation,$plus;
		}else{
			my $new=(exists $drug{lc$drug})?$drug{lc$drug}:($drug);
			push @translation,$new;
		}
	}
	return(join(",",@translation));
}

##疾病翻译信息
open DIS,"/dataseq/jmdna/codes/reportbase/cancer_type.txt";
my (%dis,%dis2);
<DIS>;
while(<DIS>){
	chomp;
	my @line=split(/\t/);
	$dis{lc$line[0]}=$line[1];
	push @{$dis2{$line[3]}},$line[0];
	push @{$dis2{$line[4]}},$line[0];	
}


if(@fusion){
	open MUT, "/dataseq/jmdna/codes/reportbase/fusion.csv";
	<MUT>;
	my %mut;
	while (<MUT>){
		my @line=split(/,/);
		$mut{$line[1]}{$line[0]}=$line[2];
	}
	
	open IN,"$output_dir/fusion/${name}.fusion.reanno.vcf";
	open POS,">$output_dir/fusion/${name}.fusion.pos.txt";
	open NEG,">$output_dir/fusion/${name}.fusion.neg.txt";
	open VUS,">$output_dir/fusion/${name}.fuison.vus.txt";
	my (@pos,@neg,@vus);
	my $h2;
	while(<IN>){
		next if /^##/;
		if (/^#CHROM/){
			$h2=$_;
			chomp $h2;
		}
		chomp;
		my @line=split(/\t/);
		if(grep{$_ eq $line[13]}@fusion or grep{$_ eq $line[14]}@fusion){
			my ($gene1,$gene2,$alt)=@line[13,14,15];
			if (not exists  $mut{"$alt Fusion"}{$gene1} and not exists  $mut{"$alt Fusion"}{$gene2}){
				push @vus,"$_\t.";
			}else{
				my $gene=(keys %{$mut{"$alt Fusion"}})[0];
				my $sig=$mut{"$alt Fusion"}{$gene};
				if ($sig=~/neutral/i){
					push @neg,"$_\t$sig"; 
				}else{					
					if (not exists $therapy{$gene}){					
						push @vus,"$_\t$sig";
					}else{
						my $bool=0;
##						
						if (exists $therapy{$gene}{"$alt Fusion"}){
							foreach my $entry(@{$therapy{$gene}{"$alt Fusion"}}){
								my @line=split("\t",$entry);
								if (($line[5] eq "FDA" or $line[5] eq "NCCN" or $line[5] eq "NMPA") and (lc$line[2] eq "solid tumor" or grep{lc$line[2] eq lc$_}@{$dis2{$cancer_type}})){
									push @pos,"$_\t$sig\t".join("\t",@line[0..9,14])."\t适应症"."\t".&drug($line[3])."\t".$dis{lc$line[2]};$bool=1;
								}elsif(($line[5] eq "FDA" or $line[5] eq "NCCN" or $line[5] eq "NMPA") and (lc$line[2] ne "solid tumor" and grep{lc$line[2] ne lc$_}@{$dis2{$cancer_type}})){
									push @pos,"$_\t$sig\t".join("\t",@line[0..9,14])."\t非适应症"."\t".&drug($line[3])."\t".$dis{lc$line[2]};$bool=1;
								}elsif(lc$line[2] eq "solid tumor" or grep{lc$line[2] eq lc$_}@{$dis2{$cancer_type}}){
									push @pos,"$_\t$sig\t".join("\t",@line[0..9,14])."\t\.\t".&drug($line[3])."\t".$dis{lc$line[2]};$bool=1;
								}
							}
						}
##
						if (exists $therapy{$gene}{"Fusion"}){
							foreach my $entry(@{$therapy{$gene}{"Fusion"}}){
								my @line=split("\t",$entry);
								if (($line[5] eq "FDA" or $line[5] eq "NCCN" or $line[5] eq "NMPA") and (lc$line[2] eq "solid tumor" or grep{lc$line[2] eq lc$_}@{$dis2{$cancer_type}})){
									push @pos,"$_\t$sig\t".join("\t",@line[0..9,14])."\t适应症"."\t".&drug($line[3])."\t".$dis{lc$line[2]};$bool=1;
								}elsif(($line[5] eq "FDA" or $line[5] eq "NCCN" or $line[5] eq "NMPA") and (lc$line[2] ne "solid tumor" and grep{lc$line[2] ne lc$_}@{$dis2{$cancer_type}})){
									push @pos,"$_\t$sig\t".join("\t",@line[0..9,14])."\t非适应症"."\t".&drug($line[3])."\t".$dis{lc$line[2]};$bool=1;
								}elsif(lc$line[2] eq "solid tumor" or grep{lc$line[2] eq lc$_}@{$dis2{$cancer_type}}){
									push @pos,"$_\t$sig\t".join("\t",@line[0..9,14])."\t\.\t".&drug($line[3])."\t".$dis{lc$line[2]};$bool=1;
								}
							}
						}
						
						push @vus,"$_\t$sig" if $bool==0;
					#	print "yes\n" if $bool==0;
					}	
				}
			}
		}
	}
	my $h=$h2."\tfun_change\t".join("\t",(split("\t",$h1))[0..9,14])."\t标签\t药物中文名\t疾病中文名";
	if(@pos){
			print POS "$h\n";
			print POS join("\n",@pos)."\n";	
	}

	if(@neg){
			print NEG $h2."\tfun_change\n";
			print NEG join("\n",@neg)."\n";	
	}

	if(@vus){
			print VUS $h2."\tfun_change\n";
			print VUS join("\n",@vus)."\n";	
	}
}


if(@longindel){
	my @pos;
	open LONGINDEL, ">$output_dir/fusion/${name}.longindel.pos.txt";
	open IN2, "$output_dir/fusion/${name}.longindel.vcf";
	my $h2;
	while(<IN2>){
		chomp;
		next if /^##/;
		if (/^#CHROM/){
			$h2=$_;
			next;
		}
		my @line=split(/\t/);
		$line[7]=~/Gene.refGene=(.*?);/;
		if (grep{$1=~/$_/}@longindel){
			if($1 eq "BCL2L11"){
				push @pos,$_ if $line[1]=='111883194';
			}else{
				push @pos,$_;
			}
		}
	}
	
	if(@pos){
			print LONGINDEL "$h2\n";
			print LONGINDEL join("\n",@pos)."\n";	
	}
}