| Title: |
Cross-oncopanel study reveals high sensitivity and accuracy with overall analytical performance depending on genomic regions |
| Authors: |
Gong, B; Li, D; Kusko, R; Novoradovskaya, N; Zhang, Y; Wang, S; Pabón-Peña, C; Zhang, Z; Lai, K; Cai, W; LoCoco, JS; Lader, E; Richmond, TA; Mittal, VK; Liu, LC; Johann, DJ; Willey, JC; Bushel, PR; Yu, Y; Xu, C; Chen, G; Burgess, D; Cawley, S; Giorda, K; Haseley, N; Qiu, F; Wilkins, K; Arib, H; Attwooll, C; Babson, K; Bao, L; Bao, W; Lucas, AB; Best, H; Bhandari, A; Bisgin, H; Blackburn, J; Blomquist, TM; Boardman, L; Burgher, B; Butler, DJ; Chang, CJ; Chaubey, A; Chen, T; Chierici, M; Chin, CR; Close, D; Conroy, J; Coleman, JC; Craig, DJ; Crawford, E; del Pozo, A; Deveson, IW; Duncan, D; Eterovic, AK; Fan, X; Foox, J; Furlanello, C; Ghosal, A; Glenn, S; Guan, M; Haag, C; Hang, X; Happe, S; Hennigan, B; Hipp, J; Hong, H; Horvath, K; Hu, J; Hung, LY; Jarosz, M; Kerkhof, J; Kipp, B; Kreil, DP; Łabaj, P; Lapunzina, P; Li, P; Li, QZ; Li, W; Li, Z; Liang, Y; Liu, S; Liu, Z; Ma, C; Marella, N; Martín-Arenas, R; Megherbi, DB; Meng, Q; Mieczkowski, PA; Morrison, T; Muzny, D; Ning, B; Parsons, BL; Paweletz, CP; Pirooznia, M; Qu, W; Raymond, A; Rindler, P; Ringler, R; Sadikovic, B; Mercer, Timothy; Thomas, David |
| Source: |
urn:ISSN:1474-7596 ; urn:ISSN:1474-760X ; Genome Biology, 22, 1, 109 |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2021 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
31 Biological Sciences; 32 Biomedical and Clinical Sciences; 3105 Genetics; Cancer; Genetics; Cancer Genomics; Human Genome; 3 Good Health and Well Being; Biomarkers; Tumor; DNA Copy Number Variations; Genetic Testing; Genomics; Humans; Molecular Diagnostic Techniques; Mutation; Neoplasms; Oncogenes; Polymorphism; Single Nucleotide; Reproducibility of Results; Sensitivity and Specificity; Analytical performance; Molecular diagnostics; Oncopanel sequencing; Precision medicine; Reproducibility; Target enrichment; anzsrc-for: 31 Biological Sciences; anzsrc-for: 32 Biomedical and Clinical Sciences |
| Description: |
Background: 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. Results: 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. Conclusion: 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://hdl.handle.net/1959.4/unsworks_77105 |
| DOI: |
10.1186/s13059-021-02315-0 |
| Availability: |
https://hdl.handle.net/1959.4/unsworks_77105; https://unsworks.unsw.edu.au/bitstreams/2bcce3a6-7a69-4c31-b40e-2a26ac53db60/download; https://doi.org/10.1186/s13059-021-02315-0 |
| Rights: |
open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ ; free_to_read |
| Accession Number: |
edsbas.98D7150D |
| Database: |
BASE |