MOLECULAR TECHNIQUES GUIDING ASSAY DESIGN | WGS
WGS Workflow
Whole-genome sequencing (WGS) provides the most comprehensive genomic view, enabling the detection of all mutation types—including rare and novel alterations—across the entire genome. This unbiased approach allows for simultaneous analysis of single nucleotide variants (SNVs), insertions/deletions, copy number alterations, structural rearrangements, and non-coding mutations, making it especially valuable for identifying new biomarkers, characterizing complex tumor subtypes, and uncovering resistance mechanisms. 20 Despite its scientific value, WGS remains rarely used in routine clinical diagnostics due to several key barriers: high sequencing and data processing costs, long turnaround times, and the requirement for WGS Comprehensive Insight, Limited Accessibility
advanced bioinformatics infrastructure and secure data storage. 21 Interpretation complexity further limits clinical adoption, as many detected variants are of uncertain significance and must be carefully reviewed by experts—using clinical databases and patient context—to determine their relevance and potential impact on diagnosis and treatment. 22 In oncology assay development, WGS is typically reserved for translational research, rare or undiagnosed cancers, or situations where targeted panels fail to yield actionable results ( Table 3 ). As sequencing technologies improve, costs decline, and AI-driven tools enhance variant interpretation, WGS may become more clinically accessible. For now, however, it remains a specialized and infrastructure- heavy option with limited scalability in commercial diagnostic workflows. 23, 24
Table 3 . Overview of CLIA-Approved WGS Assays Supporting Precision Oncology
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