DRAGEN Array v1.2.0 Release Notes

RELEASE DATE

February 2025

RELEASE HIGHLIGHTS

• Whole-genome copy number and loss of heterozygosity (LOH) calling, with VCF output format, for any human genotyping array.

• B-allele frequency bedgraph output file to power informative CNV visualizations.

• Additional outputs including ISCN and cytoband nomenclature to support cytogenetics applications.

NEW FEATURES IN DETAIL

• Cytogenetic CNV and LOH Calling and VCF Output

  • Ability to obtain output files for any human genotyping array. Detection abilities vary by array probe density and spacing.

  • Detects copy number up to 4+.

  • Provides Phred scaled quality score to assess the event quality.

  • Addition of mosaic tagging to detect mosaic deletions and duplications.

  • Three arrays tested for performance including:

    • Infinium Global Diversity Array with Cytogenetics-8

    • Infinium Global Screening Array with Cytogenetics-24

    • Infinium CytoSNP-850K BeadChip using the iScan System

  • Ability to adjust minimum size and probe number for copy number and LOH event calling

• BAF and LRR Bedgraph files

  • Additional bedgraph file output for B-allele frequency (BAF) for use in visualization. Updated file extensions to differentiate BAF.bedgraph and LRR.bedgraph files.

  • Added a smoothing parameter to the genotype gtc-to-bedgraph command for LRR.bedgraph (log R ratio bedgraph file) generation for improved visualization.

  • Bedgraph files are compatible with IGV (Integrative Genomics Viewer) for visualization purposes.

• Cytogenetic annotation and JSON Output

  • Provides summary statistics per sample and per CNV/LOH event. Includes gene count and gene names within each event based on the RefSeq database.

  • Annotates each event using International System for Human Cytogenomic Nomenclature (ISCN) 2020 and cytoband nomenclature based on Ensembl database.

• Pharmacogenomics

  • Added root command pgx for grouping PGx copy number and star allele calling.

  • Fixed issue causing pgx star-allele annotate command to fail mid-analysis from version 1.1.

KNOWN ISSUES

• If a sample's sex estimate is called as unknown in the genotyping module, the cytogenetic caller will assume the sample is male. Consequently, detection results on sex chromosomes could be inaccurate if the sample is actually female.

• ISCN annotations in the cytogenetic annotation JSON output file are only provided for variants greater than 1 Kb in length. This is often cited as a minimum size limit used to define copy number variants.

• Centromere regions typically have low sequence complexity and are prone to artifacts. As a result, cytogenetic calling results in these regions are likely to be false positives.

• The cyto annotate subcommand produces extraneous logs (e.g., No credential is provided) that can be safely ignored.

• During cyto call, there is a log for the CytoPlatform currently hardcoded to LCG regardless of the product used. This has no bearing on the underlying algorithm and is just what is reported in the log. It can be safely ignored.

KNOWN LIMITATIONS

• DRAGEN Array CNV and LOH calling is intended for constitutional samples only, oncology samples not supported at this time.

• DRAGEN Array CNV and LOH calling was only validated for specific array platforms (Infinium Global Diversity Array with Cytogenetics-8, Infinium Global Screening Array with Cytogenetics-24, Infinium CytoSNP-850K BeadChip using the iScan System).

• DRAGEN Array CNV and LOH calling may call large events that are broken into smaller pieces and require visual confirmation.

• DRAGEN Array CNV and LOH calling does not product mosaic fraction estimation or mosaic ISCN notation at this time.

• When using CytoSNP-850Kv1-4_iScan_B, GSACyto-24v1_20044998_C, or GDACyto-8v1-0_20047166_E manifests, DRAGEN Array CNV and LOH calling will be unable to call events or visualize probes in the PAR (pseudo-autosomal regions). Please reach out to [e-mail] for additional details.

• GT is hardcoded to homozygous alt (1/1) for cyto VCF entries.

• IDATs originating from NextSeq550 not tested.