Homologous Recombination Deficiency

DRAGEN Homologous Recombination Deficiency (HRD) Scoring takes in allele-specific copy number calls in either VCF format or directly streamed from somatic copy number callers. DRAGEN HRD then calculates scores for Loss of Heterozygosity (LOH), Telomeric Allelic Imbalance (TAI), and Large-Scale State Transition (LST). The three scores are output to the .hrdscore.csv file. You can only use DRAGEN HRD when inputting results from WGS somatic CNV calling or ASCN WES somatic CNV calling.

Command-Line Options

Use the following command-line options to run HRD scoring. You can run HRD scoring with somatic CNV calling or after using somatic CNV calling results.

To run HRD scoring together with somatic CNV calling, use the following options. For more CNV parameters, please refer to CNV calling.

--enable-hrd=true Set to true to enable HRD scoring to quantify genomic instability.

--enable-cnv=true Set to true to enable CNV calling to run together with HRD scoring.

To run HRD scoring after somatic CNV calling, use the following options:

--enable-hrd=true Set to true to enable HRD scoring to quantify genomic instability.

--hrd-input-ascn Specify the allele-specific copy number file (*cnv.vcf.gz). The CNV VCF file should include REF calls for proper HRD segmentation. See the option --cnv-enable-ref-calls in the CNV section.

--hrd-input-tn Specify the tumor normalized bin count file (*.tn.tsv.gz).

If reference is failed to AutoDetected, then centromere and blacklist files should be specified with following options:

--hrd-input-centromere Centromere locations per chromosome in tsv format

--hrd-input-blacklist Blacklist bed file

HRD Output

The following metrics are included in the .hrdscore.csv output file. The following is an example output file.

Sample	LOH_Score	TAI_Score	LST_Score	HRD_Score
Sample	16	17	28	61

Example command line

The following example command runs HRD end to end workflow with CNV. This is an example of Somatic WGS T/N. See the Somatic CNV section for other use cases. HRD is supported for any CNV workflows that support ASCN, and just needs to add --enable-hrd=true on top of the CNV command lines.

dragen \
-r <HASH_TABLE> \
--tumor-bam-input <TUMOR_BAM> \
--cnv-normal-b-allele-vcf <NORMAL_VCF> \
--output-directory <OUTPUT> \
--output-file-prefix <SAMPLE> \
--enable-map-align=false \
--enable-cnv=true \
--enable-hrd=true \

The following example command runs HRD standalone.

dragen \
-r <HASH_TABLE> \
--hrd-input-ascn <CNV_VCF> \
--hrd-input-tn <TN_TSV> \
--output-directory <OUTPUT> \
--output-file-prefix <SAMPLE> \
--enable-hrd=true \