Identify QIAseq DNA Somatic Variants with HRD Score (beta)

The Identify QIAseq DNA Somatic Variants with HRD Score (Illumina) (beta) template workflow has been designed to calculate a homologous recombination deficiency (HRD) score using custom QIAseq panels with enrichment of SNPs throughout the genome. The HRD score is based on detected copy number variants (CNVs) and shifts in observed allele frequencies of variants that are expected to be heterozygous.

The workflow is built on Identify QIAseq DNA Somatic Variants and only a few changes have been made compared to the original workflow. Therefore, to see a general description of this workflow and information about how to run it, go to the manual page for the Identify QIAseq DNA Variants template workflows (The Identify QIAseq DNA Variants template workflows). The changes implemented with this workflow include addition of the Detect Regional Ploidy and Calculate HRD Score (beta) tools with relevant inputs and that an input to Control mappings in the Copy Number Variant Detection tool is now mandatory. Note that only variants and target-level CNVs that overlap benchmark regions defined by the Genome in a Bottle Consortium are used as input for the Detect Regional Ploidy tool.

The Detect Regional Ploidy tool takes a target-level annotation track produced by the CNV detection tool as input. Therefore, to run this workflow, control mappings or coverage tables for establishing a CNV baseline must be available. These can be generated with the workflow Create QIAseq DNA CNV Control Mapping (Illumina), see Create QIAseq DNA CNV Control Mapping workflows.

In order to facilitate easy inspection of variants in 15 selected homologous recombination repair genes an additional variant output listing variants in target regions overlapping these genes is included.

Based on internal testing and validation of a limited number of samples, we have identified 50 as a potential HRD score cutoff for distinguishing between normal samples (below 50) and samples with HRD (equal to or above 50). Note that 50 may not be an optimal cutoff for all protocols, and should only be considered as guidance.

The reference data necessary to run this template workflow is available in the reference data set QIAseq DNA Panels hg19. However, primers and target regions for the relevant QIAseq custom panel must be configured independently. To import the target regions/roi file for a QIAseq custom panel, use Import Tracks (see To import the QIAseq custom panel primers, use Import QIAGEN Primers (see Import QIAGEN Primers).