Nature biotechnology · 2021

Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology.

СтатьяПоддержка NIH: внешняя программаResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАВалидационное исследованиеНазвание и аннотация: Перевод в очереди

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Deveson Ira W, Gong Binsheng, Lai Kevin, LoCoco Jennifer S, Richmond Todd A, Schageman Jeoffrey, Zhang Zhihong, Novoradovskaya Natalia, Willey James C, Jones Wendell, Kusko Rebecca, Chen Guangchun, Madala Bindu Swapna, Blackburn James, Stevanovski Igor, Bhandari Ambica, Close Devin, Conroy Jeffrey, Hubank Michael, Marella Narasimha, Mieczkowski Piotr A, Qiu Fujun, Sebra Robert, Stetson Daniel, Sun Lihyun, Szankasi Philippe, Tan Haowen, Tang Lin-Ya, Arib Hanane, Best Hunter, Burgher Blake, Bushel Pierre R, Casey Fergal, Cawley Simon, Chang Chia-Jung, Choi Jonathan, Dinis Jorge, Duncan Daniel, Eterovic Agda Karina, Feng Liang, Ghosal Abhisek, Giorda Kristina, Glenn Sean, Happe Scott, Haseley Nathan, Horvath Kyle, Hung Li-Yuan, Jarosz Mirna, Kushwaha Garima, Li Dan, Li Quan-Zhen, Li Zhiguang, Liu Liang-Chun, Liu Zhichao, Ma Charles, Mason Christopher E, Megherbi Dalila B, Morrison Tom, Pabón-Peña Carlos, Pirooznia Mehdi, Proszek Paula Z, Raymond Amelia, Rindler Paul, Ringler Rebecca, Scherer Andreas, Shaknovich Rita, Shi Tieliu, Smith Melissa, Song Ping, Strahl Maya, Thodima Venkat J, Tom Nikola, Verma Suman, Wang Jiashi, Wu Leihong, Xiao Wenzhong, Xu Chang, Yang Mary, Zhang Guangliang, Zhang Sa, Zhang Yilin, Shi Leming, Tong Weida, Johann Donald J, Mercer Timothy R, Xu Joshua, SEQC2 Oncopanel Sequencing Working Group

Аннотация

Circulating tumor DNA (ctDNA) sequencing is being rapidly adopted in precision oncology, but the accuracy, sensitivity and reproducibility of ctDNA assays is poorly understood. Here we report the findings of a multi-site, cross-platform evaluation of the analytical performance of five industry-leading ctDNA assays. We evaluated each stage of the ctDNA sequencing workflow with simulations, synthetic DNA spike-in experiments and proficiency testing on standardized, cell-line-derived reference samples. Above 0.5% variant allele frequency, ctDNA mutations were detected with high sensitivity, precision and reproducibility by all five assays, whereas, below this limit, detection became unreliable and varied widely between assays, especially when input material was limited. Missed mutations (false negatives) were more common than erroneous candidates (false positives), indicating that the reliable sampling of rare ctDNA fragments is the key challenge for ctDNA assays. This comprehensive evaluation of the analytical performance of ctDNA assays serves to inform best practice guidelines and provides a resource for precision oncology.

Предметные рубрики MeSH

Circulating Tumor DNA High-Throughput Nucleotide Sequencing Humans Limit of Detection Medical Oncology Neoplasms Practice Guidelines as Topic Precision Medicine Reproducibility of Results Sequence Analysis, DNA

Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology.

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Аннотация

Предметные рубрики MeSH