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vcfparser.pl
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vcfparser.pl
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#!/usr/bin/env perl
use Modern::Perl qw{ 2014 };
use warnings qw{ FATAL utf8 };
use autodie qw{ open close :all };
use v5.18;
use utf8;
use open qw{ :encoding(UTF-8) :std };
use charnames qw{ :full :short };
use Carp;
use English qw{ -no_match_vars };
use Cwd;
use FindBin qw{ $Bin };
use File::Basename qw{ basename };
use File::Spec::Functions qw{ catdir catfile devnull };
use Getopt::Long;
use Params::Check qw{ check allow last_error };
$Params::Check::PRESERVE_CASE = 1; #Do not convert to lower case
use IO::File;
## Third party module(s)
use Set::IntervalTree;
##MIPs lib/
use lib catdir( $Bin, q{lib} );
use MIP::Check::Modules qw{ check_perl_modules };
use MIP::Log::MIP_log4perl qw{ initiate_logger };
use MIP::Script::Utils qw{ help };
our $USAGE;
BEGIN {
require MIP::Check::Modules;
my @modules =
qw{ Modern::Perl autodie Set::IntervalTree Log::Log4perl MIP::Log::MIP_log4perl };
## Evaluate that all modules required are installed
check_perl_modules(
{
modules_ref => \@modules,
program_name => $PROGRAM_NAME,
}
);
$USAGE = basename($0) . qq{ infile.vcf [OPTIONS] > outfile.vcf
-pvep/--parse_vep Parse VEP transcript specific entries (Supply flag to enable)
-rf/--range_feature_file (tsv)
-rf_ac/--range_feature_annotation_columns
-sf/--select_feature_file (tsv)
-sf_mc/--select_feature_matching_column
-sf_ac/--select_feature_annotation_columns
-sof/--select_outfile (vcf)
-pad/--padding (Default: "5000" nucleotides)
-peg/--per_gene Output most severe consequence transcript (Supply flag to enable)
-wst/--write_software_tag (Default: "1")
-l/--log_file Log file (Default: "vcfparser.log")
-h/--help Display this help message
-v/--version Display version
};
}
my ( $infile, $select_feature_file, $select_feature_matching_column,
$range_feature_file, $select_outfile );
##Scalar parameters with defaults
my ( $write_software_tag, $padding, $log_file ) =
( 1, 5000, catfile( cwd(), q{vcfparser.log} ) );
##Boolean
my ( $parse_vep, $per_gene );
my ( @range_feature_annotation_columns, @select_feature_annotation_columns );
my ( %consequence_severity, %range_data, %select_data, %snpeff_cmd, %tree,
%meta_data );
my $vcfparser_version = q{1.2.13};
## Enables cmd "vcfparser.pl" to print usage help
if ( !@ARGV ) {
help(
{
USAGE => $USAGE,
exit_code => 0,
}
);
}
elsif ( ( defined($ARGV) ) && ( $ARGV[0] !~ /^-/ ) )
{ #Collect potential infile - otherwise read from STDIN
$infile = $ARGV[0];
}
###User Options
GetOptions(
'pvep|parse_vep' => \$parse_vep,
'rf|range_feature_file:s' => \$range_feature_file,
'rf_ac|range_feature_annotation_columns:s' =>
\@range_feature_annotation_columns, #Comma separated list
'sf|select_feature_file:s' => \$select_feature_file,
'sf_mc|select_feature_matching_column:n' =>
\$select_feature_matching_column,
'sf_ac|select_feature_annotation_columns:s' =>
\@select_feature_annotation_columns, #Comma separated list
'sof|select_outfile:s' => \$select_outfile,
'wst|write_software_tag:n' => \$write_software_tag,
'pad|padding:n' => \$padding,
'peg|per_gene' => \$per_gene,
'l|log_file:s' => \$log_file,
'h|help' => sub { say STDOUT $USAGE; exit; }, #Display help text
'v|version' => sub {
say STDOUT "\n" . basename($0) . " " . $vcfparser_version, "\n";
exit;
}, #Display version number
)
or help(
{
USAGE => $USAGE,
exit_code => 1,
}
);
## Creates log object
my $log = initiate_logger(
{
file_path => $log_file,
log_name => q{Vcfparser},
}
);
## Basic flag option check
if ( ( !@range_feature_annotation_columns ) && ($range_feature_file) ) {
$log->info($USAGE);
$log->fatal(
"Need to specify which feature column(s) to use with range feature file: "
. $range_feature_file
. " when annotating variants by using flag -rf_ac",
"\n"
);
exit 1;
}
if ( ( !$select_feature_matching_column ) && ($select_feature_file) ) {
$log->info($USAGE);
$log->fatal(
"Need to specify which feature column to use with select feature file: "
. $select_feature_file
. " when selecting variants by using flag -sf_mc",
"\n"
);
exit 1;
}
if ( ( !$select_outfile ) && ($select_feature_file) ) {
$log->info($USAGE);
$log->fatal(
"Need to specify which a select outfile to use when selecting variants by using flag -sof",
"\n"
);
exit 1;
}
@range_feature_annotation_columns =
split( /,/, join( ',', @range_feature_annotation_columns ) )
; #Enables comma separated annotation columns on cmd
@select_feature_annotation_columns =
split( /,/, join( ',', @select_feature_annotation_columns ) )
; #Enables comma separated annotation columns on cmd
###
#MAIN
###
define_select_data();
if ($range_feature_file) {
read_feature_file(
{
tree_href => \%tree,
feature_data_href => \%range_data,
feature_columns_ref => \@range_feature_annotation_columns,
range_file_key => "range_feature",
infile_path => $range_feature_file,
padding_ref => \$padding,
}
);
}
if ($select_feature_file) {
read_feature_file(
{
tree_href => \%tree,
feature_data_href => \%select_data,
feature_columns_ref => \@select_feature_annotation_columns,
range_file_key => "select_feature",
infile_path => $select_feature_file,
padding_ref => \$padding,
select_feature_matching_column => $select_feature_matching_column,
}
);
}
define_snpeff_annotations();
define_consequence_severity();
read_infile_vcf(
{
meta_data_href => \%meta_data,
snpeff_cmd_href => \%snpeff_cmd,
range_data_href => \%range_data,
select_data_href => \%select_data,
consequence_severity_href => \%consequence_severity,
tree_href => \%tree,
range_feature_annotation_columns_ref =>
\@range_feature_annotation_columns,
select_feature_annotation_columns_ref =>
\@select_feature_annotation_columns,
select_outfile_path => $select_outfile,
vcfparser_version => $vcfparser_version,
select_feature_file => $select_feature_file,
per_gene => $per_gene,
parse_vep => $parse_vep,
write_software_tag => $write_software_tag,
}
);
###
#Sub Routines
###
sub define_select_data {
##define_select_data
##Function : Defines arbitrary INFO fields based on headers in selectFile
##Returns : ""
##Arguments: None
$select_data{select_file}{HGNC_symbol}{info} =
q?##INFO=<ID=HGNC_symbol,Number=.,Type=String,Description="The HGNC gene symbol">?;
$select_data{select_file}{Ensembl_gene_id}{info} =
q?##INFO=<ID=Ensembl_gene_id,Number=.,Type=String,Description="Ensembl gene identifier">?;
$select_data{select_file}{OMIM_morbid}{info} =
q?##INFO=<ID=OMIM_morbid,Number=.,Type=String,Description="OMIM morbid ID associated with gene(s)">?;
$select_data{select_file}{Phenotypic_disease_model}{info} =
q?##INFO=<ID=Phenotypic_disease_model,Number=.,Type=String,Description="Known disease gene(s) phenotype inheritance model">?;
$select_data{select_file}{Clinical_db_gene_annotation}{info} =
q?##INFO=<ID=Clinical_db_gene_annotation,Number=.,Type=String,Description="Gene disease group association">?;
$select_data{select_file}{Reduced_penetrance}{info} =
q?##INFO=<ID=Reduced_penetrance,Number=.,Type=String,Description="Pathogenic gene which can exhibit reduced penetrance">?;
$select_data{select_file}{Disease_associated_transcript}{info} =
q?##INFO=<ID=Disease_associated_transcript,Number=.,Type=String,Description="Known pathogenic transcript(s) for gene">?;
$select_data{select_file}{Ensembl_transcript_to_refseq_transcript}{info} =
q?##INFO=<ID=Ensembl_transcript_to_refseq_transcript,Number=.,Type=String,Description="The link between ensembl transcript and refSeq transcript IDs">?;
$select_data{select_file}{Gene_description}{info} =
q?##INFO=<ID=Gene_description,Number=.,Type=String,Description="The HGNC gene description">?;
$select_data{select_file}{Genetic_disease_model}{info} =
q?##INFO=<ID=Genetic_disease_model,Number=.,Type=String,Description="Known disease gene(s) inheritance model">?;
$select_data{select_file}{No_hgnc_symbol}{info} =
q?##INFO=<ID=No_hgnc_symbol,Number=.,Type=String,Description="Clinically relevant genetic regions lacking a HGNC_symbol or Ensembl gene ">?;
}
sub define_snpeff_annotations {
##define_snpeff_annotations
##Function : Defines the snpEff annotations that can be parsed and modified
##Returns : ""
##Arguments: None
$snpeff_cmd{snpeff}{phastCons100way_vertebrate_prediction_term}{File} =
q?SnpSift dbnsfp?;
$snpeff_cmd{snpeff}{phastCons100way_vertebrate_prediction_term}{vcf_key} =
q?dbNSFP_phastCons100way_vertebrate?;
$snpeff_cmd{snpeff}{phastCons100way_vertebrate_prediction_term}{info} =
q?##INFO=<ID=phastCons100way_vertebrate_prediction_term,Number=A,Type=String,Description="PhastCons conservation prediction term">?;
$snpeff_cmd{snpeff}{phyloP100way_vertebrate_prediction_term}{File} =
q?SnpSift dbnsfp?;
$snpeff_cmd{snpeff}{phyloP100way_vertebrate_prediction_term}{vcf_key} =
q?dbNSFP_phyloP100way_vertebrate?;
$snpeff_cmd{snpeff}{phyloP100way_vertebrate_prediction_term}{info} =
q?##INFO=<ID=phyloP100way_vertebrate_prediction_term,Number=A,Type=String,Description="PhyloP conservation prediction term">?;
$snpeff_cmd{snpeff}{'GERP++_RS_prediction_term'}{File} = q?SnpSift dbnsfp?;
$snpeff_cmd{snpeff}{'GERP++_RS_prediction_term'}{vcf_key} =
q?dbNSFP_GERP___RS?;
$snpeff_cmd{snpeff}{'GERP++_RS_prediction_term'}{info} =
q?##INFO=<ID=GERP++_RS_prediction_term,Number=A,Type=String,Description="GERP RS conservation prediction term">?;
}
sub define_consequence_severity {
##define_consequence_severity
##Function : Defines the precedence of consequences for SO-terms
##Returns : ""
##Arguments: None
$consequence_severity{transcript_ablation}{rank} = 1;
$consequence_severity{transcript_ablation}{genetic_region_annotation} =
"exonic";
$consequence_severity{splice_donor_variant}{rank} = 2;
$consequence_severity{splice_donor_variant}{genetic_region_annotation} =
"splicing";
$consequence_severity{splice_acceptor_variant}{rank} = 2;
$consequence_severity{splice_acceptor_variant}{genetic_region_annotation} =
"splicing";
$consequence_severity{stop_gained}{rank} = 3;
$consequence_severity{stop_gained}{genetic_region_annotation} = "exonic";
$consequence_severity{frameshift_variant}{rank} = 4;
$consequence_severity{frameshift_variant}{genetic_region_annotation} =
"exonic";
$consequence_severity{stop_lost}{rank} = 5;
$consequence_severity{stop_lost}{genetic_region_annotation} = "exonic";
$consequence_severity{start_lost}{rank} = 5;
$consequence_severity{start_lost}{genetic_region_annotation} = "exonic";
$consequence_severity{initiator_codon_variant}{rank} = 6;
$consequence_severity{initiator_codon_variant}{genetic_region_annotation} =
"exonic";
$consequence_severity{inframe_insertion}{rank} = 6;
$consequence_severity{inframe_insertion}{genetic_region_annotation} =
"exonic";
$consequence_severity{inframe_deletion}{rank} = 6;
$consequence_severity{inframe_deletion}{genetic_region_annotation} =
"exonic";
$consequence_severity{missense_variant}{rank} = 6;
$consequence_severity{missense_variant}{genetic_region_annotation} =
"exonic";
$consequence_severity{protein_altering_variant}{rank} = 6;
$consequence_severity{protein_altering_variant}{genetic_region_annotation}
= "exonic";
$consequence_severity{transcript_amplification}{rank} = 7;
$consequence_severity{transcript_amplification}{genetic_region_annotation}
= "exonic";
$consequence_severity{splice_region_variant}{rank} = 8;
$consequence_severity{splice_region_variant}{genetic_region_annotation} =
"splicing";
$consequence_severity{incomplete_terminal_codon_variant}{rank} = 9;
$consequence_severity{incomplete_terminal_codon_variant}
{genetic_region_annotation} = "exonic";
$consequence_severity{synonymous_variant}{rank} = 10;
$consequence_severity{synonymous_variant}{genetic_region_annotation} =
"exonic";
$consequence_severity{stop_retained_variant}{rank} = 10;
$consequence_severity{stop_retained_variant}{genetic_region_annotation} =
"exonic";
$consequence_severity{start_retained_variant}{rank} = 10;
$consequence_severity{start_retained_variant}{genetic_region_annotation} =
"exonic";
$consequence_severity{coding_sequence_variant}{rank} = 11;
$consequence_severity{coding_sequence_variant}{genetic_region_annotation} =
"exonic";
$consequence_severity{mature_miRNA_variant}{rank} = 12;
$consequence_severity{mature_miRNA_variant}{genetic_region_annotation} =
"ncRNA_exonic";
$consequence_severity{'5_prime_UTR_variant'}{rank} = 13;
$consequence_severity{'5_prime_UTR_variant'}{genetic_region_annotation} =
"5UTR";
$consequence_severity{'3_prime_UTR_variant'}{rank} = 14;
$consequence_severity{'3_prime_UTR_variant'}{genetic_region_annotation} =
"3UTR";
$consequence_severity{non_coding_transcript_exon_variant}{rank} = 15;
$consequence_severity{non_coding_transcript_exon_variant}
{genetic_region_annotation} = "ncRNA_exonic";
$consequence_severity{non_coding_transcript_variant}{rank} = 15;
$consequence_severity{non_coding_transcript_variant}
{genetic_region_annotation} = "ncRNA";
$consequence_severity{intron_variant}{rank} = 16;
$consequence_severity{intron_variant}{genetic_region_annotation} =
"intronic";
$consequence_severity{NMD_transcript_variant}{rank} = 17;
$consequence_severity{NMD_transcript_variant}{genetic_region_annotation} =
"ncRNA";
$consequence_severity{upstream_gene_variant}{rank} = 18;
$consequence_severity{upstream_gene_variant}{genetic_region_annotation} =
"upstream";
$consequence_severity{downstream_gene_variant}{rank} = 19;
$consequence_severity{downstream_gene_variant}{genetic_region_annotation} =
"downstream";
$consequence_severity{TFBS_ablation}{rank} = 20;
$consequence_severity{TFBS_ablation}{genetic_region_annotation} = "TFBS";
$consequence_severity{TFBS_amplification}{rank} = 21;
$consequence_severity{TFBS_amplification}{genetic_region_annotation} =
"TFBS";
$consequence_severity{TF_binding_site_variant}{rank} = 22;
$consequence_severity{TF_binding_site_variant}{genetic_region_annotation} =
"TFBS";
$consequence_severity{regulatory_region_variant}{rank} = 22;
$consequence_severity{regulatory_region_variant}{genetic_region_annotation}
= "regulatory_region";
$consequence_severity{regulatory_region_ablation}{rank} = 23;
$consequence_severity{regulatory_region_ablation}{genetic_region_annotation}
= "regulatory_region";
$consequence_severity{regulatory_region_amplification}{rank} = 24;
$consequence_severity{regulatory_region_amplification}
{genetic_region_annotation} = "regulatory_region";
$consequence_severity{feature_elongation}{rank} = 25;
$consequence_severity{feature_elongation}{genetic_region_annotation} =
"genomic_feature";
$consequence_severity{feature_truncation}{rank} = 26;
$consequence_severity{feature_truncation}{genetic_region_annotation} =
"genomic_feature";
$consequence_severity{intergenic_variant}{rank} = 27;
$consequence_severity{intergenic_variant}{genetic_region_annotation} =
"intergenic"
}
sub read_feature_file {
##read_feature_file
##Function : Reads a file containg features to be annotated using range queries e.g. EnsemblGeneID. Adds to Metadata hash and creates Interval tree for feature.
##Returns : ""
##Arguments: $tree_href, $feature_data_href, $feature_columns_ref, $range_file_key, $infile_path, $padding_ref, $select_feature_matching_column
## : $tree_href => Interval tree hash {REF}
## : $feature_data_href => Range file hash {REF}
## : $feature_columns_ref => Range columns to include {REF}
## : $range_file_key => Range file key used to seperate range file(s) i.e., select and range
## : $infile_path => Infile path
## : $padding_ref => Padding distance {REF}
## : $select_feature_matching_column => Column in the select file to match with vcf key annotation {Optional}
my ($arg_href) = @_;
## Flatten argument(s)
my $tree_href;
my $feature_data_href;
my $feature_columns_ref;
my $range_file_key;
my $infile_path;
my $padding_ref;
my $select_feature_matching_column;
my $tmpl = {
tree_href => {
required => 1,
defined => 1,
default => {},
strict_type => 1,
store => \$tree_href
},
feature_data_href => {
required => 1,
defined => 1,
default => {},
strict_type => 1,
store => \$feature_data_href
},
feature_columns_ref => {
required => 1,
defined => 1,
default => [],
strict_type => 1,
store => \$feature_columns_ref
},
range_file_key => {
required => 1,
defined => 1,
strict_type => 1,
store => \$range_file_key
},
infile_path => {
required => 1,
defined => 1,
strict_type => 1,
store => \$infile_path
},
padding_ref => {
required => 1,
defined => 1,
default => \$$,
strict_type => 1,
store => \$padding_ref
},
select_feature_matching_column =>
{ strict_type => 1, store => \$select_feature_matching_column },
};
check( $tmpl, $arg_href, 1 ) or die qw[Could not parse arguments!];
## Retrieve logger object now that log_file has been set
my $log = Log::Log4perl->get_logger("Vcfparser");
my @headers; #Save headers from rangeFile
my $FILEHANDLE = IO::Handle->new(); #Create anonymous filehandle
open( $FILEHANDLE, "<", $infile_path )
or $log->logdie( "Cannot open " . $infile_path . ":" . $!, "\n" );
while (<$FILEHANDLE>) {
chomp $_; #Remove newline
if (m/^\s+$/) { # Avoid blank lines
next;
}
if ( $_ =~ /^##/ ) { #MetaData - Avoid
next;
}
if ( $_ =~ /^#/ ) { #Header/Comment
@headers = split( /\t/, $_ );
for (
my $extract_columns_counter = 0 ;
$extract_columns_counter < scalar(@$feature_columns_ref) ;
$extract_columns_counter++
)
{ #Defines what scalar to store
my $header_ref =
\$headers[ $$feature_columns_ref[$extract_columns_counter] ]
; #Alias
add_meta_data_info(
{
meta_data_href => $feature_data_href,
range_file_key => $range_file_key,
header_ref => $header_ref,
position_ref => \$extract_columns_counter,
range_file_path_ref => \$infile_path,
}
);
}
next;
}
if ( $_ =~ /^(\S+)/ ) {
my @line_elements =
split( "\t", $_ ); #Loads range file line elements
if ( defined($select_feature_matching_column) ) {
$line_elements[$select_feature_matching_column] =~
s/\s/_/g; # Replace whitespace with "_"
$select_data{ $line_elements[$select_feature_matching_column] }
= $line_elements[$select_feature_matching_column];
}
## Create Interval Tree
if (@$feature_columns_ref)
{ #Annotate vcf with features from range file
feature_annotations(
{
tree_href => $tree_href,
feature_columns_ref => $feature_columns_ref,
line_elements_ref => \@line_elements,
range_file_key => $range_file_key,
padding_ref => $padding_ref,
}
);
}
}
}
close($FILEHANDLE);
$log->info(
"Finished reading " . $range_file_key . " file: " . $infile_path );
}
sub read_infile_vcf {
##read_infile_vcf
##Function : Reads infile in vcf format and adds and parses annotations
##Returns : ""
##Arguments: $meta_data_href, $snpeff_cmd_href, $range_data_href, $select_data_href, $consequence_severity_href, $tree_href, $range_feature_annotation_columns_ref, $select_feature_annotation_columns_ref, $select_outfile_path, $vcfparser_version, $select_feature_file, $parse_vep, $write_software_tag, $per_gene_ref
## : $meta_data_href => Vcf meta data {REF}
## : $snpeff_cmd_href => SnpEff meta data {REF}
## : $range_data_href => Range file data {REF}
## : $select_data_href => Select file data {REF}
## : $consequence_severity_href => Consequence severity for SO-terms {REF}
## : $tree_href => Interval tree hash {REF}
## : $range_feature_annotation_columns_ref => Range feature columns {REF}
## : $select_feature_annotation_columns_ref => Select feature columns {REF}
## : $select_outfile_path => The select file path
## : $vcfparser_version => vcfParser version
## : $select_feature_file => The select feature file
## : $parse_vep => Parse VEP output
## : $write_software_tag => Write software tag to vcf header switch
## : $per_gene => Only collect most severe transcript per gene
my ($arg_href) = @_;
## Default(s)
my $select_feature_file;
my $parse_vep;
my $write_software_tag;
## Flatten argument(s)
my $meta_data_href;
my $snpeff_cmd_href;
my $range_data_href;
my $select_data_href;
my $consequence_severity_href;
my $tree_href;
my $range_feature_annotation_columns_ref;
my $select_feature_annotation_columns_ref;
my $select_outfile_path;
my $vcfparser_version;
my $per_gene;
my $tmpl = {
meta_data_href => {
required => 1,
defined => 1,
default => {},
strict_type => 1,
store => \$meta_data_href
},
snpeff_cmd_href => {
required => 1,
defined => 1,
default => {},
strict_type => 1,
store => \$snpeff_cmd_href
},
range_data_href => {
required => 1,
defined => 1,
default => {},
strict_type => 1,
store => \$range_data_href
},
select_data_href => {
required => 1,
defined => 1,
default => {},
strict_type => 1,
store => \$select_data_href
},
consequence_severity_href => {
required => 1,
defined => 1,
default => {},
strict_type => 1,
store => \$consequence_severity_href
},
tree_href => {
required => 1,
defined => 1,
default => {},
strict_type => 1,
store => \$tree_href
},
range_feature_annotation_columns_ref => {
required => 1,
defined => 1,
default => [],
strict_type => 1,
store => \$range_feature_annotation_columns_ref
},
select_feature_annotation_columns_ref => {
required => 1,
defined => 1,
default => [],
strict_type => 1,
store => \$select_feature_annotation_columns_ref
},
select_outfile_path =>
{ strict_type => 1, store => \$select_outfile_path },
vcfparser_version => {
required => 1,
defined => 1,
strict_type => 1,
store => \$vcfparser_version
},
select_feature_file => {
default => 0,
strict_type => 1,
store => \$select_feature_file
},
per_gene => {
default => 0,
allow => [ undef, 0, 1 ],
strict_type => 1,
store => \$per_gene
},
parse_vep => {
default => 0,
allow => [ undef, 0, 1 ],
strict_type => 1,
store => \$parse_vep
},
write_software_tag => {
default => 1,
allow => [ 0, 1 ],
strict_type => 1,
store => \$write_software_tag
},
};
check( $tmpl, $arg_href, 1 ) or die qw[Could not parse arguments!];
## Retrieve logger object now that log_file has been set
my $log = Log::Log4perl->get_logger("Vcfparser");
my $FILEHANDLE =
IO::Handle->new(); #Create anonymous filehandle for select file
my @vep_format_fields;
my %vep_format_field_column;
my %vcf_header;
my @vcf_format_columns; #Catch #vcf header #CHROM line
if ($select_feature_file) {
open( $FILEHANDLE, ">", $select_outfile_path )
or $log->logdie( "Cannot open " . $select_outfile_path . ":" . $!,
"\n" );
}
while (<>) {
chomp $_; # Remove newline
if (m/^\s+$/) { # Avoid blank lines
next;
}
if ( $_ =~ /^##(\S+)=/ ) { # MetaData
parse_meta_data(
{
meta_data_href => $meta_data_href,
meta_data_string => $_,
}
);
if ( $_ =~ /INFO\=\<ID\=(\w+)/ ) { # Collect all INFO keys
$vcf_header{info}{$1} = $1; #Save to hash
}
if ( $_ =~ /SnpSiftCmd\=/ ) { #Find SnpEff command meta line
for my $database ( keys %{ $snpeff_cmd_href->{snpeff} } ) {
if ( $_ =~ /$snpeff_cmd_href->{snpeff}{$database}{File}/ )
{ #SnpEff/Sift has been used to annotate input vcf
unless ( defined( $vcf_header{info}{$database} ) )
{ #Unless INFO header is already present add to meta_dataHeader
$snpeff_cmd_href->{present}{database}{$database} =
$database
; #Save which frequency db has been used for later
push(
@{ $meta_data_href->{info}{$database} },
$snpeff_cmd_href->{snpeff}{$database}{info}
);
if (
defined(
$snpeff_cmd_href->{snpeff}{$database}
{fix_info}
)
)
{ #If FIX_INFO flag is present add to meta_dataHeader
push(
@{
$meta_data_href->{fix_info}{$database}
},
$snpeff_cmd_href->{snpeff}{$database}
{fix_info}
);
}
}
}
}
next;
}
if ( $_ =~ /INFO\=\<ID\=CSQ/ ) { #Find VEP INFO Field
if ( $_ =~ /Format:\s(\S+)"\>/ )
{ #Locate Format within VEP INFO meta line
@vep_format_fields = split( /\|/, $1 );
while ( my ( $field_index, $field ) =
each(@vep_format_fields) )
{
$vep_format_field_column{$field} =
$field_index; #Save the order of VEP features
}
}
if ($parse_vep) {
if ( ( $vep_format_field_column{HGNC_ID} )
&& ( $vep_format_field_column{Consequence} ) )
{
push(
@{
$meta_data_href->{info}{most_severe_consequence}
},
'##INFO=<ID=most_severe_consequence,Number=.,Type=String,Description="Most severe genomic consequence.">'
);
}
}
next;
}
next;
}
if ( $_ =~ /^#CHROM/ ) {
@vcf_format_columns = split( /\t/, $_ ); #Split vcf format line
add_feature_file_meta_data_to_vcf(
{
meta_data_href => $meta_data_href,
vcf_header_href => \%vcf_header,
feature_annotation_columns_ref =>
$range_feature_annotation_columns_ref,
data_href => $range_data_href,
file_key => "Range",
}
);
add_feature_file_meta_data_to_vcf(
{
meta_data_href => $meta_data_href,
vcf_header_href => \%vcf_header,
feature_annotation_columns_ref =>
$select_feature_annotation_columns_ref,
data_href => $select_data_href,
file_key => "Select",
}
);
if ($write_software_tag) {
add_program_to_meta_data_header(
{
meta_data_href => $meta_data_href,
vcfparser_version => $vcfparser_version,
}
);
}
if ($select_feature_file) { #SelectFile annotations
write_meta_data(
{
meta_data_href => $meta_data_href,
FILEHANDLE => *STDOUT,
SELECTFILEHANDLE => $FILEHANDLE,
}
);
say STDOUT $_; #Write #CHROM header line
say $FILEHANDLE $_; #Write #CHROM header line
}
else {
write_meta_data(
{
meta_data_href => $meta_data_href,
FILEHANDLE => *STDOUT,
}
);
say STDOUT $_; #Write #CHROM header line
}
next;
}
if ( $_ =~ /^(\S+)/ ) {
my %record;
my %consequence;
my %noid_region;
my $variant_line;
my $selected_variant_line;
my @line_elements = split( "\t", $_ ); #Loads vcf file elements
##Check that we have an INFO field
unless ( $line_elements[7] ) {
$log->fatal( "No INFO field at line number: " . $. );
$log->fatal( "Displaying malformed line: " . $_ );
exit 1;
}
##Add line elements to record hash
while ( my ( $element_index, $element ) = each(@line_elements) ) {
$record{ $vcf_format_columns[$element_index] } =
$element; #Link vcf format headers to the line elements
}
my @info_elements = split( /;/, $record{INFO} ); #Add INFO elements
## Collect key value pairs in INFO field
foreach my $element (@info_elements) {
my @key_value_pairs =
split( "=", $element ); #key index = 0 and value index = 1
$record{INFO_key_value}{ $key_value_pairs[0] } =
$key_value_pairs[1];
}
for my $database ( keys %{ $snpeff_cmd_href->{present}{database} } )
{ #Note that the vcf should only contain 1 database entry
my $vcf_key = $snpeff_cmd_href->{snpeff}{$database}{vcf_key};
if ( $record{INFO_key_value}{$vcf_key} ) {
my @allele_scores =
split( ",", $record{INFO_key_value}{$vcf_key} )
; #Split on ","
my $conservation_term;
if ( $database eq
"phastCons100way_vertebrate_prediction_term" )
{
$conservation_term = find_conserved(
{
elements_ref => \@allele_scores,
score_cutoff => 0.8,
}
);
}
if (
$database eq "phyloP100way_vertebrate_prediction_term" )
{
$conservation_term = find_conserved(
{
elements_ref => \@allele_scores,
score_cutoff => 2.5,
}
);
}
if ( $database eq "GERP++_RS_prediction_term" ) {
$conservation_term = find_conserved(
{
elements_ref => \@allele_scores,
score_cutoff => 2,
}
);
}
if ( defined($conservation_term) ) {
## Save database info
$record{INFO_addition}{$database} = $conservation_term;
}
}
}
## Checks if an interval tree exists (per chr) and collects features from input array and adds annotations to line
%noid_region = tree_annotations(
{
tree_href => $tree_href,
data_href => $select_data_href,
record_href => \%record,
line_elements_ref => \@line_elements,
range_file_key => "select_feature",
}
)
; #noid_region is only for selectfile since all variants are passed to research file
## Checks if an interval tree exists (per chr) and collects features from input array and adds annotations to line
tree_annotations(
{
tree_href => $tree_href,
data_href => $range_data_href,
record_href => \%record,
range_file_key => "range_feature",
line_elements_ref => \@line_elements,
}
);
if ($parse_vep) {
parse_vep_csq(
{
record_href => \%record,
vep_format_field_column_href =>
\%vep_format_field_column,
select_data_href => $select_data_href,
consequence_href => \%consequence,
consequence_severity_href => $consequence_severity_href,
per_gene => $per_gene,
}
);