DRAGEN Array v1.1.0 Release Notes

RELEASE DATE

September 2024

RELEASE HIGHLIGHTS

• New EX PGx beadchips enabled for PGx analysis

• Increased coverage of high priority PGx genes

• Custom optimized .egt files accepted in PGx analysis

• Up-to-date database reflecting latest versions of public PGx resources

• DPWG guidelines now available for metabolizer status calling on cloud analysis

NEW FEATURES IN DETAIL

• DRAGEN Array supports multiple PGx products

  • Two new EX PGx beadchips enabled through genotyping, PGx CNV calling, and star allele annotation

    • Infinium Global Screening Array with Enhanced PGx-48 v4.0 Kit

    • Infinium Global Clinical Research Array with Enhanced PGx-24 v1.0 Kit

  • In total 3 PGx products supported

    Product	Manifest Name	Genome Build	Product Files Link
    GDA-ePGx	GDA_PGx-8v1-0_20042614_G2	38	GDA-ePGx product files
    GSAv4-ePGx	GSA-PGx-48v4-0_20079540_E2	38	GSAv4-ePGx product files
    GCRA-ePGx	GCRA-PGx-24v1-0_20084467_C2	38	GCRA-ePGx product files

• Increased coverage of high priority PGx genes

  • Star allele annotation now covers CYP2E1, CYP1A2, ABCG2, CYP2C8, HMGCR, UGT1A4, UGT2B15, F13A1, and HLA-B*15:02

  • CNV calling now covers SULT1A1

  • Extended bi-allelic PGx variants from source databases to multi-allelic variants based on the designs in the supported PGx products.

  • See PGx Star Allele Coverage and PGx CNV Coverage for the full coverage lists.

• Allows flexibility for GTCs generated with a custom cluster file (.egt) to be used with the commercial CN model file (.dat). This alleviates the burden to retrain the CN model file.

  • The cluster file is a required input for the genotype call command in DRAGEN Array. The CN (Copy Number) model file is a required input to the copy-number call command to enable accurate copy number calling for pharmacogenomics. Custom cluster files and CN model files may be required for optimal genotyping and PGx performance. See section Optimizing cluster files and copy number models for additional details.

• Database revision reflecting PGx Allele Definitions and PGx Guidelines updates.

• Standardization of star allele JSON output file

  • Renamed databaseSources to phenotypeDatabaseSources and starAlleleDatabaseSources

  • Renamed Phenotype to PhenotypeDatabaseAnnotation

  • Combined missingVariants and allMissingVariants to missingVariantSites

  • JSONized supportingVariants and missingVariants at the gene and candidate solution allele levels

  • Removed redundant info in the Alleles fields

• Updated VCF tabix indexing, improving performance and disk usage for SNV VCF.

KNOWN ISSUES

• Some simple variants have REF and ALT delimited by _ instead of > in the star_alleles.csv and metabolizer status JSON files (e.g., "ryr1.38577931a_c" instead of "ryr1.38577931a>c")

• Some multi-nucleotide variant (MNV) designs reverse compliment the "Allele1/2 Top" fields in the Final Report

• Occasional star-allele solution score discorcordance between Linux and Windows OS with concordant solution ranking.

• Rare intermittent memory issues during star allele calling. Example error message: The model has been changed since the solution was last computed.. To workaround the issue, user should restart star allele calling or run it on a machine with more memory.

KNOWN LIMITATIONS

• Star allele calling does not support novel alleles but those defined in the PharmVar and PharmGKB databases.

• CYP2D6 non-*36 star alleles with exon 9 conversion, such as *83, are reported as *36 with *83 as an underlying allele.

• Genotyping only supports diploid organisms. Polyploid genotyping is currently not supported.

• DRAGEN Array were only validated and intended to be used for commercial PGx beadchips with specified manifests (see table above). PGx star allele annotation is not backwards compatable with v1.0 manifest version, e.g., GDA_PGx-8v1-0_20042614_E2 is supported in DRAGEN Array v1.0, GDA_PGx-8v1-0_20042614_G2 is supported in DRAGEN Array v1.1.

• Command line options unsquash-duplicates and filter-loci for gtc-to-vcf conversion should not be used when star allele calling is desired. In addition, VCFs must be gzipped and tabix indexed (the default for gtc-to-vcf) to be used in star allele calling.