DRAGEN Array v1.0.0 Release Notes

RELEASE DATE

December 2023

RELEASE HIGHLIGHTS

• Improved star allele calling accuracy for Global Diversity Array with enhanced PGx (GDA-ePGx) BeadChips.

• Reports star allele calls with quality scores for greater transparency and confidence.

• Provides missing variant reporting to improve data quality.

NEW FEATURES IN DETAIL

• Star Allele Calling

  • Star allele calling for genes listed in PGx Star Allele Coverage

    • For in-silico datasets, call rate ≥99%, diplotyping accuracy ≥ 90%

    • Includes reporting of the hybrid star alleles and allelic specific copy number

  • Provides quality score that estimates confidence in the star allele call as an additional quality metric

  • Star allele call rate increased through more robust error tolerance and missing data tolerance

    • Supporting variants and missing variants are listed and can be further reviewed

    • Quality score indicates confidence in result considering the missing data

  • Reports alternative ranked PGx star allele solutions

    • Allows an alternative to be investigated which may be desirable for samples with low confidence calls

    • Provides quality score (negative log likelihood) for alternative solutions

• Function annotations for PGx genes listed in section PGx Allele Definitions and PGx Guidelines

  • Metabolizer and function annotations are supported for two sets of guidelines from CPIC and DPWG respectively

  • Activity scores are provided for CYP2C9, CYP2D6, and DPYD

• CNV VCF

  • CNV coverage for genes listed in PGx CNVs Coverage

  • Compressed and indexed files for size reduction and faster reading

  • Updated VCF header description to indicate copy number of 5 may be reported by the software

  • Revised filter field delimiter to comply with VCF 4.3 specification which allows VCF parsing software to parse the file successfully

• Genotyping VCF

  • Compressed and indexed files for size reduction and faster reading

KNOWN ISSUES

• Corrupt or invalid GTC files will abort with an error instead of skipping. The corrupt or invalid GTC files will need to be removed before proceeding.

• In the gtc-to-vcf subcommand a mismatch between BPM and CSV manifests will not cause the command to abort with an error. The mismatch will need to be addressed before proceeding.

• For gtc-to-vcf, multi-allelic variants designed with multiple assays might not always collapse into one variant correctly and be reported as two separate variants instead. Some indel variants are missing from SNV VCF due to mapping issue between the designed indels and the reference genome.

• Manifest names greater than 80 characters will cause failure when converting IDATs to GTCs.

• Symbolic links for VCFs are not supported as the inputs to the “star-allele call” subcommand.

• The local Linux CLI and Cloud offering do not sort the star_alleles.csv and various fields in the metabolizer_status.json. The local Windows CLI does.

KNOWN LIMITATIONS

• PGx CNV calling and star allele calling and annotation were only validated and intended to be used with GDA_PGx_E2 product files.

• Using subcommands “unsquash-duplicates” and “filter loci” during gtc-to-vcf conversion should not be used when star allele calling is desired.

• Only CPIC guidelines are available for star allele annotation (metabolizer status calling) for the cloud offering. For local, CPIC and DPWG are available.