ORCID Profile
0000-0002-9625-5731
Current Organisation
University of Toledo College of Medicine
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Publications
Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions
Publisher: Springer Science and Business Media LLC
Date: 16-04-2021
DOI: 10.1186/S13059-021-02315-0
Abstract: Targeted sequencing using oncopanels requires comprehensive assessments of accuracy and detection sensitivity to ensure analytical validity. By employing reference materials characterized by the U.S. Food and Drug Administration-led SEquence Quality Control project phase2 (SEQC2) effort, we perform a cross-platform multi-lab evaluation of eight Pan-Cancer panels to assess best practices for oncopanel sequencing. All panels demonstrate high sensitivity across targeted high-confidence coding regions and variant types for the variants previously verified to have variant allele frequency (VAF) in the 5–20% range. Sensitivity is reduced by utilizing VAF thresholds due to inherent variability in VAF measurements. Enforcing a VAF threshold for reporting has a positive impact on reducing false positive calls. Importantly, the false positive rate is found to be significantly higher outside the high-confidence coding regions, resulting in lower reproducibility. Thus, region restriction and VAF thresholds lead to low relative technical variability in estimating promising biomarkers and tumor mutational burden. This comprehensive study provides actionable guidelines for oncopanel sequencing and clear evidence that supports a simplified approach to assess the analytical performance of oncopanels. It will facilitate the rapid implementation, validation, and quality control of oncopanels in clinical use.
Advancing NGS quality control to enable measurement of actionable mutations in circulating tumor DNA
Publisher: Elsevier BV
Date: 11-2021
A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency
Publisher: Springer Science and Business Media LLC
Date: 16-04-2021
DOI: 10.1186/S13059-021-02316-Z
Abstract: Oncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference s les having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten erse cancer cell lines in idually and their pool, termed S le A, to develop a reference s le with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance. In reference S le A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5–100× more than existing commercially available s les. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference S le B can be admixed with S le A to create new s les with a similar number of known variants at much lower allele frequency than what exists in S le A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels. These new reference s les and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.
Related Organisations
University Of Toledo College Of Medicine
Location: United States of America
Related Funding Activities
No related grants have been discovered for Daniel Craig.