September 2024
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
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
GDA-ePGx
GDA_PGx-8v1-0_20042614_G2
38
GSAv4-ePGx
GSA-PGx-48v4-0_20079540_E2
38
GCRA-ePGx
GCRA-PGx-24v1-0_20084467_C2
38
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.
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.
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.