#!/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'} ? $ENV{'DATABASE'} : "/dataseq/jmdna/codes/reportbase";
print "Fusion药物注释使用路径：$database_path\n";

open MUT, "$database_path/fusion.csv";
<MUT>;
my %mut;
while (<MUT>) {
    my @line = split(/,/);
    $mut{$line[1]}{$line[0]} = $line[2];
}

open THERAPY, "$database_path/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, "$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 IN, "$input";
open POS, ">$output.pos.txt";
open NEG, ">$output.neg.txt";
open VUS, ">$output.vus.txt";

my $h2 = <IN>;
chomp $h2;

print POS $h2 . "\tOncogenic\t" . join("\t", (split("\t", $h1))[0 .. 9, 14]) . "\tLabel\tDrugCn\tIndication\n";
print NEG $h2 . "\tOncogenic\n";
print VUS $h2 . "\tOncogenic\n";

my (@pos, @neg, @vus);
my @column_names = split('\t', $h2);
while (<IN>) {
    chomp;
    my @splitline = split(/\t/);

    # 将数据与表头对应
    my %record;
    @record{@column_names} = @splitline;
    if (not exists $mut{"$record{'FUSION'} Fusion"}{$record{'GENE1'}} and not exists $mut{"$record{'FUSION'} Fusion"}{$record{'GENE2'}}) {
        push @vus, "$_\t.";
    }
    else {
        my $gene = (keys %{$mut{"$record{'FUSION'} Fusion"}})[0];
        my $sig = $mut{"$record{'FUSION'} 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}{"$record{'FUSION'} Fusion"}) {
                    foreach my $entry (@{$therapy{$gene}{"$record{'FUSION'}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;
            }
        }
    }
}

if (@pos) {

    print POS join("\n", @pos) . "\n";
}

if (@neg) {

    print NEG join("\n", @neg) . "\n";
}

if (@vus) {

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