#!/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 THERAPY,"/dataseq/jmdna/codes/reportbase/targetTherapy.txt";
my $h1=<THERAPY>;
chomp $h1;
my %therapy;
my $cancer_type=$ARGV[4];
while(<THERAPY>){
	chomp;
	my @line=split("\t");
	push @{$therapy{$line[0]}{$line[1]}},$_ if (($line[1] eq "Deletion" or $line[1] eq "Amplification") 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];
}


open INFO,"$codes_dir/info.txt";
<INFO>;
while (<INFO>){
    chomp;
    my @line=split(/\t/,$_);
    if ($line[0] eq $project){		
		if($line[5] ne "NA"){
			my @cnv_target=split(/\//,$line[5]);
			open POS,">$output_dir/cnvkit/${name}.cnv.pos.txt";
			open VUS,">$output_dir/cnvkit/${name}.cnv.vus.txt";
			my (@pos,@vus,@cnv_detected);
			open IN,"$output_dir/cnvkit/${name}.rmdup.cns";
			my $h2=<IN>;
			chomp $h2;
			while(<IN>){
				chomp;
				my @line2=split(/\t/);
				my @cnv_detected=split(/,/,$line2[3]);
				my %uniq;
				foreach my $cnv_detected(@cnv_detected){
					$uniq{$cnv_detected}++;
					next if $uniq{$cnv_detected}>1;
					if (grep{$cnv_detected eq $_}@cnv_target){
						my $bool=0;
						my $cn=sprintf("%.1f",2**(1+$line2[4]));
						if($cn>=4 and exists $therapy{$cnv_detected}{'Amplification'}){
							foreach my $entry(@{$therapy{$cnv_detected}{'Amplification'}}){
								my @line=split("\t",$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,"$_\t$cn\tOncogenic\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,"$_\t$cn\tOncogenic\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$cn\tOncogenic\t".join("\t",@line[0..9,14])."\t\.\t".&drug($line[3])."\t".$dis{lc$line[2]};$bool=1;
								}
							}
						}elsif($cn==0 and exists $therapy{$cnv_detected}{'Deletion'}){
							foreach my $entry(@{$therapy{$cnv_detected}{'Deletion'}}){
								my @line=split("\t",$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,"$_\t$cn\tOncogenic\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,"$_\t$cn\tOncogenic\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$cn\tOncogenic\t".join("\t",@line[0..9,14])."\t\.\t".&drug($line[3])."\t".$dis{lc$line[2]};$bool=1;
								}
							}
						}else{
							push @vus,"$_\t$cn\t.";
						}
						if($bool==0){
							push @vus,"$_\t$cn\t.";
						}
					}
				}
			}
			if(@pos){
				my $h=$h2."\tcn\tfun_change\t".join("\t",(split("\t",$h1))[0..9,14])."\t标签\t药物中文名\t疾病中文名";
				print POS "$h\n";
				print POS join("\n",@pos)."\n";	
			}

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