小柯机器人

美国食品药品监督管理局Wenming Xiao等研究人员合作建立使用全基因组测序检测癌症突变的评估标准。相关论文于2021年9月9日发表在《自然—生物技术》杂志上。

研究人员报道了从配对的肿瘤-正常基因组DNA（gDNA）样本中获得的参考调用集，这些样本来自一个乳腺癌细胞系（其高度异质性，具有非整倍体基因组，并富含体细胞改变）和一个匹配的淋巴细胞系。研究人员通过不同测序平台的全外显子组测序（WES）和覆盖率大于2,000倍的靶向测序，部分验证了这些调用集的体细胞突变和生殖系变异，并高置信度地跨越了82%的基因组区域。

尽管gDNA参考样本不能代表临床样本的原生癌细胞，但在建立测序流水线时，它们不仅能最大限度地减少技术、检测和信息学的潜在偏差，还能为"纯肿瘤"或"匹配的肿瘤-正常"分析提供独特的基准资源。

据悉，用于生成标准化DNA数据集来建立测序管线的样本缺乏，或对不同算法性能的基准测试限制了癌症基因组学的实施和应用。

附：英文原文

Title: Establishing community reference samples, data and call sets for benchmarking cancer mutation detection using whole-genome sequencing

Author: Fang, Li Tai, Zhu, Bin, Zhao, Yongmei, Chen, Wanqiu, Yang, Zhaowei, Kerrigan, Liz, Langenbach, Kurt, de Mars, Maryellen, Lu, Charles, Idler, Kenneth, Jacob, Howard, Zheng, Yuanting, Ren, Luyao, Yu, Ying, Jaeger, Erich, Schroth, Gary P., Abaan, Ogan D., Talsania, Keyur, Lack, Justin, Shen, Tsai-Wei, Chen, Zhong, Stanbouly, Seta, Tran, Bao, Shetty, Jyoti, Kriga, Yuliya, Meerzaman, Daoud, Nguyen, Cu, Petitjean, Virginie, Sultan, Marc, Cam, Margaret, Mehta, Monika, Hung, Tiffany, Peters, Eric, Kalamegham, Rasika, Sahraeian, Sayed Mohammad Ebrahim, Mohiyuddin, Marghoob, Guo, Yunfei, Yao, Lijing, Song, Lei, Lam, Hugo Y. K., Drabek, Jiri, Vojta, Petr, Maestro, Roberta, Gasparotto, Daniela, Kks, Sulev, Reimann, Ene, Scherer, Andreas, Nordlund, Jessica, Liljedahl, Ulrika, Jensen, Roderick V., Pirooznia, Mehdi, Li, Zhipan, Xiao, Chunlin, Sherry, Stephen T., Kusko, Rebecca, Moos, Malcolm, Donaldson, Eric, Tezak, Zivana, Ning, Baitang, Tong, Weida, Li, Jing, Duerken-Hughes, Penelope, Catalanotti, Claudia, Maheshwari, Shamoni, Shuga, Joe, Liang, Winnie S., Keats, Jonathan, Adkins, Jonathan, Tassone, Erica, Zismann, Victoria

Issue&Volume: 2021-09-09

Abstract: The lack of samples for generating standardized DNA datasets for setting up a sequencing pipeline or benchmarking the performance of different algorithms limits the implementation and uptake of cancer genomics. Here, we describe reference call sets obtained from paired tumor–normal genomic DNA (gDNA) samples derived from a breast cancer cell line—which is highly heterogeneous, with an aneuploid genome, and enriched in somatic alterations—and a matched lymphoblastoid cell line. We partially validated both somatic mutations and germline variants in these call sets via whole-exome sequencing (WES) with different sequencing platforms and targeted sequencing with >2,000-fold coverage, spanning 82% of genomic regions with high confidence. Although the gDNA reference samples are not representative of primary cancer cells from a clinical sample, when setting up a sequencing pipeline, they not only minimize potential biases from technologies, assays and informatics but also provide a unique resource for benchmarking ‘tumor-only’ or ‘matched tumor–normal’ analyses.

DOI: 10.1038/s41587-021-00993-6

Source: https://www.nature.com/articles/s41587-021-00993-6

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex