The following versions of DRAGEN Array have been released:
December 2023
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.
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
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.
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.
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
| Product | Manifest Name | Genome Build | Product Files Link |
|---|---|---|---|
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.
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
May 2024
Adjustable thresholds to determine pass/fail status
Data summary plots for a quick visual check of each analysis batch
Determining detection p-value, beta-values, and m-values from each methylation sample
Deployment on BaseSpace™ Sequence Hub user interface for easy analysis kickoff
Adjustable thresholds for 21 built in controls, p-value detection, proportion probes passing, and offset correction within BaseSpace Sequence Hub to customize for user’s study needs
Thresholds are used to assign pass (1) or fail (0) status to each sample
Failed metrics can be highlighted for easy viewing
Pinpoint areas of failure including bisulfite conversion, staining, hybridization, etc. to identify assay steps in need of troubleshooting
Quantitative values for each control removing ambiguity with manual interpretation
Data summary plots with information on passing p-value detection and principal component analysis of beta values
Provides detection p-value, beta-values and m-values for each CG site per sample to use in downstream analysis
Standard thresholds may not be applicable for all discontinued, semi-custom or custom BeadChips and IDATs originating from NextSeq550
Built-in controls may not be available on all discontinued, semi-custom or custom BeadChips
March 2024
Ability to genotype and produce related reports for human and non-human arrays in the cloud.
Configureable interfaces in Basespace that allows for flexibility and easy kick off.
Some multi-nucleotide variant (MNV) designs reverse compliment the "Allele1/2 Top" fields in the Final Report
Genotyping only works on diploid organisms at this time. Polyploid genotyping is not currently supported.