A Concordance Study among 26 NGS Laboratories Participating in the NCI Molecular Analysis for Therapy Choice Clinical Trial.
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Zane Linda K, Yee Laura M, Chang Ting-Chia, Sklar Jeffrey, Yang Guangxiao, Wen Jia Di, Li Peining, Harrington Robin, Sims David J, Harper Kneshay, Trent Jeffrey M, LoBello Janine R, Szelinger Szabolcs, Benson Kasey, Zeng Jia, Poorman Kelsey, Xu Danbin, Frampton Garrett M, Pavlick Dean C, Miller Vincent A, Tandon Bevan, Swat Wojciech, Weiss Lawrence, Funari Vincent Anthony, Conroy Jeffrey M, Prescott James L, Chandra Pranil K, Ma Charles, Champion Kristen J, Baschkopf Gregory X, Fesko Yuri A, Freitas Tracey Allen K, Tomlins Scott A, Hovelson Daniel H, White Kevin, Sorrells Shelly, Tell Robert, Beaubier Nike, King David, Li Lei, Kelly Kevin, Uvalic Jasmina, Meyers Bridgette, Kolhe Ravindra, Lindeman Neal I, Baltay Michele, Sholl Lynette M, Lopategui Jean, Vail Eric, Zhang Wenjuan, Telatar Milhan, Afkhami Michelle, Hsiao Susan J, Mansukhani Mahesh M, Adams Emily, Jiang LiQun, NCI-MATCH Designated Laboratories, Aldape Kenneth D, Raffeld Mark, Xi Liqiang, for NCI-COMPASS Team, Stehr Henning, Segal Jeremy P, Aisner Dara L, Davies Kurtis D, Brown Noah A, Livingston Robert J, Konnick Eric Q, Song Wei, Solomon James P, Walther Zenta, for NCI-MATCH Designated Laboratories, McShane Lisa M, Harris Lyndsay N, Chen Alice P, Tsongalis Gregory J, Hamilton Stanley R, Flaherty Keith T, O'Dwyer Peter J, Conley Barbara A, Patton David R, Iafrate A John, Williams P Mickey, Tricoli James V, Karlovich Chris
Аннотация
EXPERIMENTAL DESIGN: Twenty-eight NGS assays from 26 laboratories within the NCI-MATCH Network, including the NCI-MATCH central laboratory (CL) and 11 commercial and 14 academic designated laboratories (DL), were used for this study. DNA from eight cell lines and two clinical samples were sequenced. Pairwise comparisons in variant detection and reporting between each DL and CL were performed for single-nucleotide variant, insertion and deletion, and copy-number variant classes.
RESULTS: We observed high concordance in variant detection between CL and DL for single-nucleotide variants and insertions and deletions [average positive agreement (APA) > 95.4% for all pairwise comparisons] but lower concordance for variant reporting after analysis pipeline filtering. We observed much higher agreement between CL and assays using amplification as the target enrichment method (84.2% < APA ≤ 95.7%, average APA = 88.7%) than other assays using hybridization capture (69.7% < APA ≤ 93.8%, average APA = 77.4%) due to blacklisting of actionable variants in low complexity regions. For copy-number variant reporting, we observed high agreement (APA > 82%) except between CL and two assays (APA = 76.9% and 71.4%) due to differences in estimation of copy numbers. Notably, for all variants, differences in variant interpretation also contributed to reporting discrepancies.
CONCLUSIONS: This study indicates that different NGS tumor profiling tests currently in widespread clinical use achieve high concordance between assays in variant detection. For variant reporting, observed discrepancies are mainly introduced during the bioinformatic analysis.