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Update SpliceAI header and add output option #756

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Update SpliceAI header and add output option #756

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103 changes: 64 additions & 39 deletions SpliceAI.pm
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Original file line number Diff line number Diff line change
Expand Up @@ -36,6 +36,7 @@ limitations under the License.
A VEP plugin that retrieves pre-calculated annotations from SpliceAI.
SpliceAI is a deep neural network, developed by Illumina, Inc
that predicts splice junctions from an arbitrary pre-mRNA transcript sequence.
By default, this plugin appends all scores from SpliceAI files.

Delta score of a variant, defined as the maximum of (DS_AG, DS_AL, DS_DG, DS_DL),
ranges from 0 to 1 and can be interpreted as the probability of the variant being
Expand All @@ -53,33 +54,36 @@ limitations under the License.
https://www.ncbi.nlm.nih.gov/pubmed/30661751

Running options:
(1) By default, this plugin appends all scores from SpliceAI files.
(2) Besides the pre-calculated scores, it can also be specified a score
cutoff between 0 and 1.

cutoff : Only return the scores for the speficied cutoff
Accepted values are between 0 and 1

split_output : Return each type of score in a different header.
This is easier for parsing the output file.

Output:
The output includes the gene symbol, delta scores (DS) and delta positions (DP)
for acceptor gain (AG), acceptor loss (AL), donor gain (DG), and donor loss (DL).

- For tab the output contains one header 'SpliceAI_pred' with all
- For tab the output contains one header "SpliceAI_pred" with all
the delta scores and positions. The format is:
'SYMBOL|DS_AG|DS_AL|DS_DG|DS_DL|DP_AG|DP_AL|DP_DG|DP_DL'
"SYMBOL|DS_AG|DS_AL|DS_DG|DS_DL|DP_AG|DP_AL|DP_DG|DP_DL"

- For JSON the output is a hash with the following format:
"spliceai":
{"DP_DL":0,"DS_AL":0,"DP_AG":0,"DS_DL":0,"SYMBOL":"X","DS_AG":0,"DP_AL":0,"DP_DG":0,"DS_DG":0}

- For VCF output the delta scores and positions are stored in different headers.
The values are 'SpliceAI_pred_xx' being 'xx' the score/position.
Example: 'SpliceAI_pred_DS_AG' is the delta score for acceptor gain.
- For VCF output and option 'split_output' the delta scores and positions are stored in different headers.
The values are "SpliceAI_pred_xx" being "xx" the score/position.
Example: "SpliceAI_pred_DS_AG" is the delta score for acceptor gain.

Gene matching:
SpliceAI can contain scores for multiple genes that overlap a variant,
and VEP can also predict consequences on multiple genes for a given variant.
The plugin only returns SpliceAI scores for the gene symbols that match (if any).

If plugin is run with option 2, the output also contains a flag: 'PASS' if delta score
passes the cutoff, 'FAIL' otherwise.
If plugin is run with option 2, the output also contains a flag: "PASS" if delta score
passes the cutoff, "FAIL" otherwise.

The following steps are necessary before running this plugin:

Expand All @@ -98,6 +102,7 @@ limitations under the License.
The plugin can then be run:
./vep -i variations.vcf --plugin SpliceAI,snv=/path/to/spliceai_scores.raw.snv.hg38.vcf.gz,indel=/path/to/spliceai_scores.raw.indel.hg38.vcf.gz
./vep -i variations.vcf --plugin SpliceAI,snv=/path/to/spliceai_scores.raw.snv.hg38.vcf.gz,indel=/path/to/spliceai_scores.raw.indel.hg38.vcf.gz,cutoff=0.5
./vep -i variations.vcf --plugin SpliceAI,snv=/path/to/spliceai_scores.raw.snv.hg38.vcf.gz,indel=/path/to/spliceai_scores.raw.indel.hg38.vcf.gz,split_output=1

=cut

Expand Down Expand Up @@ -141,36 +146,56 @@ sub new {
$output_vcf = 1;
}

if(defined($param_hash->{split_output})) {
$self->{split_output} = 1;
}

return $self;
}

sub feature_types {
return ['Transcript'];
return ["Transcript"];
}

sub get_header_info {
my $self = shift;

my %header;

if($output_vcf) {
$header{'SpliceAI_pred_SYMBOL'} = 'SpliceAI gene symbol';
$header{'SpliceAI_pred_DS_AG'} = 'SpliceAI predicted effect on splicing. Delta score for acceptor gain';
$header{'SpliceAI_pred_DS_AL'} = 'SpliceAI predicted effect on splicing. Delta score for acceptor loss';
$header{'SpliceAI_pred_DS_DG'} = 'SpliceAI predicted effect on splicing. Delta score for donor gain';
$header{'SpliceAI_pred_DS_DL'} = 'SpliceAI predicted effect on splicing. Delta score for donor loss';
$header{'SpliceAI_pred_DP_AG'} = 'SpliceAI predicted effect on splicing. Delta position for acceptor gain';
$header{'SpliceAI_pred_DP_AL'} = 'SpliceAI predicted effect on splicing. Delta position for acceptor loss';
$header{'SpliceAI_pred_DP_DG'} = 'SpliceAI predicted effect on splicing. Delta position for donor gain';
$header{'SpliceAI_pred_DP_DL'} = 'SpliceAI predicted effect on splicing. Delta position for donor loss';
# Get the SpliceAI tool version from one of the files
my $spliceai_version;
my $spliceai_file = $self->{_files}[0];
open(my $fh, "gzip -dc $spliceai_file |") or die "Could not open '$spliceai_file': $!";
while (my $line = <$fh>) {
last if $line !~ /^#/;
if ($line =~ /^##INFO/) {
if ($line =~ /(SpliceAIv[\d.]+)/) {
$spliceai_version = $1;
}
}
}
close($fh);

$header{"SpliceAI_tool_version"} = $spliceai_version;

if($output_vcf || $self->{split_output}) {
$header{"SpliceAI_pred_SYMBOL"} = "SpliceAI gene symbol";
$header{"SpliceAI_pred_DS_AG"} = "SpliceAI predicted effect on splicing. Delta score for acceptor gain";
$header{"SpliceAI_pred_DS_AL"} = "SpliceAI predicted effect on splicing. Delta score for acceptor loss";
$header{"SpliceAI_pred_DS_DG"} = "SpliceAI predicted effect on splicing. Delta score for donor gain";
$header{"SpliceAI_pred_DS_DL"} = "SpliceAI predicted effect on splicing. Delta score for donor loss";
$header{"SpliceAI_pred_DP_AG"} = "SpliceAI predicted effect on splicing. Delta position for acceptor gain";
$header{"SpliceAI_pred_DP_AL"} = "SpliceAI predicted effect on splicing. Delta position for acceptor loss";
$header{"SpliceAI_pred_DP_DG"} = "SpliceAI predicted effect on splicing. Delta position for donor gain";
$header{"SpliceAI_pred_DP_DL"} = "SpliceAI predicted effect on splicing. Delta position for donor loss";
}

else {
$header{'SpliceAI_pred'} = 'SpliceAI predicted effect on splicing. These include delta scores (DS) and delta positions (DP) for acceptor gain (AG), acceptor loss (AL), donor gain (DG), and donor loss (DL). Format: SYMBOL|DS_AG|DS_AL|DS_DG|DS_DL|DP_AG|DP_AL|DP_DG|DP_DL';
$header{"SpliceAI_pred"} = "SpliceAI predicted effect on splicing. These include delta scores (DS) and delta positions (DP) for acceptor gain (AG), acceptor loss (AL), donor gain (DG), and donor loss (DL). Format: SYMBOL|DS_AG|DS_AL|DS_DG|DS_DL|DP_AG|DP_AL|DP_DG|DP_DL";
}

if($self->{cutoff}) {
$header{'SpliceAI_cutoff'} = 'Flag if delta score pass the cutoff (PASS) or if it does not (FAIL)';
$header{"SpliceAI_cutoff"} = "Flag if delta score pass the cutoff (PASS) or if it does not (FAIL)";
}

return \%header;
Expand All @@ -189,7 +214,7 @@ sub run {

return {} unless(@data);

my $result_data = '';
my $result_data = "";
my $result_flag;

# Store all SpliceAI results
Expand Down Expand Up @@ -218,34 +243,34 @@ sub run {
if ($start == $data_value->{start} && $ref_allele eq $data_value->{ref} && $alt_allele eq $data_value->{alt}) {
my %hash;

if($output_vcf || $self->{config}->{output_format} eq "json" || $self->{config}->{rest}) {
if($output_vcf || $self->{config}->{output_format} eq "json" || $self->{config}->{rest} || $self->{split_output}) {
my @data_values = split /\|/, $data_value->{result};
my $prefix ="";
my $prefix = "";
$prefix = "SpliceAI_pred_" if $output_vcf;
$hash{$prefix. 'SYMBOL'} = $data_values[0];
$hash{$prefix. 'DS_AG'} = $data_values[1];
$hash{$prefix. 'DS_AL'} = $data_values[2];
$hash{$prefix. 'DS_DG'} = $data_values[3];
$hash{$prefix. 'DS_DL'} = $data_values[4];
$hash{$prefix. 'DP_AG'} = $data_values[5];
$hash{$prefix. 'DP_AL'} = $data_values[6];
$hash{$prefix. 'DP_DG'} = $data_values[7];
$hash{$prefix. 'DP_DL'} = $data_values[8];
$hash{$prefix. "SYMBOL"} = $data_values[0];
$hash{$prefix. "DS_AG"} = $data_values[1];
$hash{$prefix. "DS_AL"} = $data_values[2];
$hash{$prefix. "DS_DG"} = $data_values[3];
$hash{$prefix. "DS_DL"} = $data_values[4];
$hash{$prefix. "DP_AG"} = $data_values[5];
$hash{$prefix. "DP_AL"} = $data_values[6];
$hash{$prefix. "DP_DG"} = $data_values[7];
$hash{$prefix. "DP_DL"} = $data_values[8];
}

else {
$hash{'SpliceAI_pred'} = $data_value->{result};
$hash{"SpliceAI_pred"} = $data_value->{result};
}

# Add a flag if cutoff is used
if($self->{cutoff}) {
if($data_value->{info} >= $self->{cutoff}) {
$result_flag = 'PASS';
$result_flag = "PASS";
}
else {
$result_flag = 'FAIL';
$result_flag = "FAIL";
}
$hash{'SpliceAI_cutoff'} = $result_flag;
$hash{"SpliceAI_cutoff"} = $result_flag;
}

$hash_aux{$data_value->{gene}} = \%hash;
Expand Down