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

die "useage:perl $0 input output cancer_type" unless @ARGV == 3;

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

my $database_path = defined $ENV{'DATABASE'} ? $ENV{'DATABASE'} : "/dataseq/jmdna/codes/reportbase";
print "Cnv药物注释使用路径：$database_path\n";

open THERAPY, "$database_path/targetTherapy.txt";
my $h1 = <THERAPY>;
chomp $h1;
my %therapy;
while (<THERAPY>) {
    chomp;
    my @line = split("\t");
    push @{$therapy{lc $line[0]}{lc $line[1]}}, $_ if (($line[1] eq "Deletion" or $line[1] eq "Amplification") and $line[9] ne 'D' and $line[2] !~ /Leukemia|Lymphoma|Myeloid/i);
}


##药物翻译信息
open DRUG, "$database_path/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));
}


open DIS, "$database_path/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}};
}

open POS, ">$output.pos.txt";
open VUS, ">$output.vus.txt";

my (@pos, @vus, @cnv_detected);
open IN, "$input";
my $h2 = <IN>;
chomp $h2;

my $h = $h2 . "\tcn\tfun_change\t" . join("\t", (split("\t", $h1))[0 .. 9, 14]) . "\tLabel\tDrugCn\tIndication";
print POS "$h\n";
print VUS "$h\n";;

while (<IN>) {
    chomp;
    my @line2 = split(/\t/);
    @cnv_detected = split(/,/, $line2[3]);
    my %uniq;
    foreach my $cnv_detected (@cnv_detected) {
        $uniq{$cnv_detected}++;
        next if $uniq{$cnv_detected} > 1;
        my $bool = 0;
        my $cn = int(0.5 + 2 ** (1 + $line2[4]));
        if ($cn >= 4 and exists $therapy{lc $cnv_detected}{lc 'Amplification'}) {
            foreach my $entry (@{$therapy{lc $cnv_detected}{lc 'Amplification'}}) {
                my @line = split("\t", $entry);
                if (!defined($line[16])) {
                    $line[16] = '';
                }

                my $dises;
                if (!(exists $dis{lc $line[2]})) {
                    $dises = 'unknow';
                }
                else {
                    $dises = $dis{lc $line[2]};
                }
                if (($line[14] eq 'A') and (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" . $dises . "\t" . $line[16];
                    $bool = 1;
                }
                elsif (($line[14] eq 'A') 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" . $dises . "\t" . $line[16];
                    $bool = 1;
                }
                elsif (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" . $dises . "\t" . $line[16];
                    $bool = 1;
                }
            }
        }
        elsif ($cn == 0 and exists $therapy{lc $cnv_detected}{lc 'Deletion'}) {
            foreach my $entry (@{$therapy{lc $cnv_detected}{lc 'Deletion'}}) {
                my @line = split("\t", $entry);
                my $dises;
                if (!(exists $dis{lc $line[2]})) {
                    $dises = 'unknow';
                }
                else {
                    $dises = $dis{lc $line[2]};
                }
                if (($line[14] eq 'A') and (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" . $dises . "\t" . $line[16];
                    $bool = 1;
                }
                elsif (($line[14] eq 'A') 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" . $dises . "\t" . $line[16];
                    $bool = 1;
                }
                elsif (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" . $dises . "\t" . $line[16];
                    $bool = 1;
                }
            }
        }
        else {
            push @vus, "$_\t$cn\t.";
        }
        if ($bool == 0) {
            push @vus, "$_\t$cn\t.";
        }
    }
}
if (@pos) {
    print POS join("\n", @pos) . "\n";
}

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