Clinical validation of a high-performance somatic exome sequencing assay: from target-enrichment strategy to variant calling.

NPJ genomic medicine
Authors
Abstract

Clinical whole-exome sequencing (WES) has revolutionized clinical diagnostics by enabling scalable, cost-effective molecular profiling to detect somatic variants and identify novel therapeutic targets. In particular, the clinical evaluation of somatic variants relies on both high-quality sequencing data and robust variant detection with rapid turnaround times. We developed an updated WES workflow utilizing a co-developed Twist Bioscience targeting panel and the DRAGEN (Dynamic Read Analysis for GENomics) platform, benchmarked with cell line mixtures containing >40,000 simulated variants and a clinical cohort of FFPE tumor specimens. Our assay, the Ó³»­´«Ã½ Clinical Somatic Whole Exome Assay V6.0, demonstrated high sensitivity (96.9% for SNVs with variant allele fraction [VAF] >10% at ≥125X; 93.5% for InDels with VAF > 20% at ≥125X) and low false positive rates (0.04 and 0.01 per Mb, respectively). The assay meets clinical requirements and enables large-scale, accurate variant profiling of cancers, expanding opportunities for molecular diagnostics across diverse clinical settings.

Year of Publication
2026
Journal
NPJ genomic medicine
Date Published
04/2026
ISSN
2056-7944
DOI
10.1038/s41525-026-00569-w
PubMed ID
41963325
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