#!/usr/bin/env perl
use strict;
use warnings;
die "useage:perl $0 input longvcf_input output longvcf_output project cancer_type" unless @ARGV == 6;

my ($input, $longvcf_input, $output, $longvcf_output, $project, $cancer_type) = @ARGV;

my $public_path = defined $ENV{'PUBLIC'} ? $ENV{'PUBLIC'} : "/dataseq/jmdna/codes/public/";
open INFO, "$public_path/info.csv";
<INFO>;
my (@fusion, @longindel);
while (<INFO>) {
    chomp;
    my @line = split(/,/, $_);
    if ($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[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));
}
=pod
##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];	
}
=cut
open DIS, "/dataseq/jmdna/codes/reportbase/oncotree.cancertype.20230801.txt";
<DIS>;
my (%dis, @id, %dis2);
while (<DIS>) {
    chomp;
    my @line = split(/\t/);
    $dis{lc $line[2]} = $line[3];
    $dis{lc $line[4]} = $line[5];
    push @{$dis2{$line[0]}}, lc $line[2];
    push @{$dis2{$line[0]}}, lc $line[4];
    push @id, $line[0];
}
foreach my $ID ($cancer_type) {
    my @family;
    my @ids = split("", $ID);
    for (my $i = 1; $i < @ids; $i = $i + 2) {
        push @family, join("", @ids[0 .. $i]);
    }
    push @family, (grep {/^$ID/} @id);
    foreach my $t (@family) {
        push @{$dis2{$ID}}, @{$dis2{$t}};
    }
}
foreach my $key (keys(%dis2)) {
    my %uniq;
    @{$dis2{$key}} = grep {++$uniq{$_} < 2} @{$dis2{$key}};
}

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, "$input";
    open POS, ">$output.fusion.pos.txt";
    open NEG, ">$output.fusion.neg.txt";
    open VUS, ">$output.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[14] eq 'A') and (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[14] eq 'A') 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 (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[14] eq 'A') and (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[14] eq 'A') 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 (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;
                    }
                }
            }
        }
    }
    my $h = $h2 . "\tOncogenic\t" . join("\t", (split("\t", $h1))[0 .. 9, 14]) . "\tLabel\tDrugCn\tIndication";
    if (@pos) {
        print POS "$h\n";
        print POS join("\n", @pos) . "\n";
    }

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

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

if (@longindel) {
    my @pos;
    open LONGINDEL, ">$longvcf_output";
    open IN2, "$longvcf_input";
    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";
    }
}