From 2f82fa49bfe07ea06cfed8bcc7c201cbafd154ef Mon Sep 17 00:00:00 2001
From: Cyriac Kandoth <ckandoth@gmail.com>
Date: Tue, 8 Aug 2017 12:00:42 -0400
Subject: [PATCH] Fix: VCFs need semicolon delim FILTER data, and header lines

---
 maf2vcf.pl | 8 ++++++--
 vcf2maf.pl | 4 ++--
 vcf2vcf.pl | 4 ++--
 3 files changed, 10 insertions(+), 6 deletions(-)

diff --git a/maf2vcf.pl b/maf2vcf.pl
index f58b678..bc0d40c 100644
--- a/maf2vcf.pl
+++ b/maf2vcf.pl
@@ -53,7 +53,7 @@
 
 # Before anything, let's parse the headers of this supposed "MAF-like" file and do some checks
 my $maf_fh = IO::File->new( $input_maf ) or die "ERROR: Couldn't open input MAF: $input_maf!\n";
-my ( %uniq_regions, %flanking_bps, @tn_pair, %col_idx, $header_line );
+my ( %uniq_regions, %filter_tags, %flanking_bps, @tn_pair, %col_idx, $header_line );
 while( my $line = $maf_fh->getline ) {
 
     # If the file uses Mac OS 9 newlines, quit with an error
@@ -89,10 +89,12 @@
     ( %col_idx ) or die "ERROR: Couldn't find a header line (must start with Hugo_Symbol, Chromosome, or Tumor_Sample_Barcode): $input_maf\n";
 
     # For each variant in the MAF, parse out the locus for running samtools faidx later
-    my ( $chr, $pos, $ref ) = map{ my $c = lc; ( defined $col_idx{$c} ? $cols[$col_idx{$c}] : "" )} qw( Chromosome Start_Position Reference_Allele );
+    my ( $chr, $pos, $ref, $filter ) = map{ my $c = lc; ( defined $col_idx{$c} ? $cols[$col_idx{$c}] : "" )} qw( Chromosome Start_Position Reference_Allele FILTER );
     $ref =~ s/^(\?|-|0)+$//; # Blank out the dashes (or other weird chars) used with indels
     my $region = "$chr:" . ( $pos - 1 ) . "-" . ( $pos + length( $ref ));
     $uniq_regions{$region} = 1;
+    # Also track the unique FILTER tags seen, so we can construct VCF header lines for each
+    map{ $filter_tags{$_} = 1 unless( $_ eq "PASS" or $_ eq "." )} split( /,|;/, $filter );
 }
 $maf_fh->close;
 
@@ -152,6 +154,7 @@
                 $tn_vcf{$vcf_file} .= "##FORMAT=<ID=GT,Number=1,Type=String,Description=\"Genotype\">\n";
                 $tn_vcf{$vcf_file} .= "##FORMAT=<ID=AD,Number=G,Type=Integer,Description=\"Allelic depths of REF and ALT(s) in the order listed\">\n";
                 $tn_vcf{$vcf_file} .= "##FORMAT=<ID=DP,Number=1,Type=Integer,Description=\"Total read depth across this site\">\n";
+                $tn_vcf{$vcf_file} .= "##FILTER=<ID=$_,Description=\"\">\n" foreach ( sort keys %filter_tags );
                 $tn_vcf{$vcf_file} .= "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT\t$t_id\t$n_id\n";
             }
 
@@ -304,6 +307,7 @@
 $vcf_fh->print( "##FORMAT=<ID=GT,Number=1,Type=String,Description=\"Genotype\">\n" );
 $vcf_fh->print( "##FORMAT=<ID=AD,Number=G,Type=Integer,Description=\"Allelic Depths of REF and ALT(s) in the order listed\">\n" );
 $vcf_fh->print( "##FORMAT=<ID=DP,Number=1,Type=Integer,Description=\"Read Depth\">\n" );
+$vcf_fh->print( "##FILTER=<ID=$_,Description=\"\">\n" ) foreach ( sort keys %filter_tags );
 $vcf_fh->print( "#CHROM\tPOS\tID\tREF\tALT\tQUAL\tFILTER\tINFO\tFORMAT\t" . join("\t", @vcf_cols) . "\n" );
 
 # Write each variant into the multi-sample VCF
diff --git a/vcf2maf.pl b/vcf2maf.pl
index 7a0e134..17ab171 100644
--- a/vcf2maf.pl
+++ b/vcf2maf.pl
@@ -769,7 +769,7 @@ sub GetBiotypePriority {
     # Copy FILTER from input VCF, and tag calls with high allele counts in any ExAC subpopulation
     my $subpop_count = 0;
     # Remove existing common_variant tags from input, so it's redefined by our criteria here
-    $filter = join( ",", grep{ $_ ne "common_variant" } split( ",", $filter ));
+    $filter = join( ";", grep{ $_ ne "common_variant" } split( /,|;/, $filter ));
     foreach my $subpop ( qw( AFR AMR EAS FIN NFE OTH SAS )) {
         if( $maf_line{"ExAC_AC_AN_$subpop"} ) {
             my ( $subpop_ac ) = split( "/", $maf_line{"ExAC_AC_AN_$subpop"} );
@@ -777,7 +777,7 @@ sub GetBiotypePriority {
         }
     }
     if( $subpop_count > 0 ) {
-        $filter = (( $filter eq "PASS" or $filter eq "." or !$filter ) ? "common_variant" : "$filter,common_variant" );
+        $filter = (( $filter eq "PASS" or $filter eq "." or !$filter ) ? "common_variant" : "$filter;common_variant" );
     }
     $maf_line{FILTER} = $filter;
 
diff --git a/vcf2vcf.pl b/vcf2vcf.pl
index 812eaf6..bac2a34 100644
--- a/vcf2vcf.pl
+++ b/vcf2vcf.pl
@@ -300,7 +300,7 @@
     # Add more filter tags to the FILTER field, if --add-filters was specified
     if( $add_filters ) {
         my %tags = ();
-        map{ $tags{$_} = 1 unless( $_ eq "PASS" or $_ eq "." )} split( ",", $filter );
+        map{ $tags{$_} = 1 unless( $_ eq "PASS" or $_ eq "." )} split( /,|;/, $filter );
         $tags{LowTotalDepth} = 1 if(( $tum_info{DP} ne "." and $tum_info{DP} < $min_tum_depth ) or ( $nrm_info{DP} ne "." and $nrm_info{DP} < $min_nrm_depth ));
         my @tum_depths = split( /,/, $tum_info{AD} );
         my @nrm_depths = split( /,/, $nrm_info{AD} );
@@ -308,7 +308,7 @@
         my $nrm_alt_depth = $nrm_depths[$var_allele_idx];
         $tags{LowTumorSupport} = 1 if( $tum_alt_depth ne "." and $tum_alt_depth < $min_tum_support );
         $tags{HighNormalSupport} = 1 if( $nrm_alt_depth ne "." and $nrm_alt_depth > $max_nrm_support );
-        my $tags_to_add = join( ",", sort keys %tags );
+        my $tags_to_add = join( ";", sort keys %tags );
         $filter = ( $tags_to_add ? $tags_to_add : $filter );
     }