Analyzing Performance of the Twist Exome with CNV Backbone at Various Probe Densities Leveraging Golden Helix VS-CNV Recap

         February 22, 2024

In our recent webcast, we unveiled the integration of the Twist Bioscience Exome 2.0 Plus Comprehensive Exome Spike-in capture panel with VS-CNV, marking a significant advancement in genetic diagnostics. By addressing the limitations of standard exome kits that miss vast genomic regions, our enhanced panel introduces ‘backbone’ probes for comprehensive genomic coverage. This innovation enables the detection of CNVs, LOH, and other genetic variations with a remarkable 100% sensitivity rate for known CNV events. Our findings, set to be shared at the ACMG 2024 conference, underscore the potential of this technology to streamline genetic testing, offering a promising alternative to conventional assays and paving the way for the future of clinical genetic diagnostics.

Clinical Whole Exome Sequencing (WES) offers a high diagnostic yield test by detecting pathogenic variants in all coding genes of the human genome. WES is poised to consolidate multiple genetic tests by accurately identifying Copy Number Variation (CNV) events, typically necessitating microarray analyses. However, standard commercial exome kits are limited to targeting exon coding regions, leaving significant gaps in coverage between genes which hinders comprehensive CNV detection and breakpoint determination.

Addressing this need for comprehensive coverage, Twist Bioscience has developed an enhanced Twist Exome 2.0 Plus Comprehensive Exome Spike-in capture panel with added “backbone” probes. These probes target common SNPs polymorphic in multiple populations and are evenly distributed in the intergenic and intronic regions, with three varying densities at 25kb, 50kb, and 100kb intervals. This backone enables the genome-wide detection of CNVs and loss of heterozygosity (LOH), on top of single nucleotide variations (SNVs) and small insertions and deletions (InDels) that come with Twist Exome 2.0 product offering. In this webcast, we evaluated the combined efficacy of the backbone-probe enhanced exome capture panel and VS-CNV 2.6 in identifying known CNVs using the Copy Number Variation Panel from the Coriell Institute’s NIGMS Human Genetic Cell Repository.

The integration of the enhanced capture panel with VS-CNV 2.6 achieved a 100% sensitivity rate for the detection of known CNV events at all three probe densities. The application of best-practice quality metrics and filters was shown to have a minimal impact on this high sensitivity. The findings underscore the potential of the augmented Twist Exome panel in tandem with the VS-CNV caller. This combination presents a promising alternative to conventional microarray assays, potentially obviating the need for additional testing in clinical CNV detection.

These findings will be presented during a poster session at the upcoming American College of Medical Genetics and Genomics (ACMG) 2024 conference. Check out our poster or stop by our booth to see a live demo showcasing VarSeq’s comprehensive CNV analysis capabilities. We look forward to seeing you there!

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