小柯机器人

美国麻省理工学院和哈佛大学布罗德研究所Viktor A. Adalsteinsson团队近期取得重要工作进展，他们研究使用具有高灵敏度的CODEC测序工具来检测单双链DNA突变。相关研究成果2023年4月27日在线发表于《自然—遗传学》杂志上。

据介绍，从单个DNA分子中检测突变在许多领域都至关重要，但具有挑战性。下一代测序（NGS）提供了巨大的通量，但不能直接对双链DNA分子（“单双链”）进行测序，以辨别两链上的真正突变。

研究人员开发了用于纠错的级联原始双链（CODEC）工具，它赋予NGS单链分辨率。CODEC提供了比NGS高1000倍的准确度，使用的读数比双链测序少100倍。CODEC显示39岁个体的精子中突变频率为2.72 × 10⁻⁸，血细胞中体细胞突变随年龄增长而增加。CODEC检测到来自单个DNA分子的全基因组克隆性造血突变、来自肿瘤基因组和液体活检的单个突变双链体、灵敏度和突变特征高10倍的微卫星不稳定性，以及读数低100倍的特异性肿瘤突变。

总之，CODEC能够进行更精确的基因检测，并揭示生物学上显著的突变，这些突变通常被NGS错误所掩盖。

附：英文原文

Title: Single duplex DNA sequencing with CODEC detects mutations with high sensitivity

Author: Bae, Jin H., Liu, Ruolin, Roberts, Eugenia, Nguyen, Erica, Tabrizi, Shervin, Rhoades, Justin, Blewett, Timothy, Xiong, Kan, Gydush, Gregory, Shea, Douglas, An, Zhenyi, Patel, Sahil, Cheng, Ju, Sridhar, Sainetra, Liu, Mei Hong, Lassen, Emilie, Skytte, Anne-Bine, Groska-Pski, Marta, Shoag, Jonathan E., Evrony, Gilad D., Parsons, Heather A., Mayer, Erica L., Makrigiorgos, G. Mike, Golub, Todd R., Adalsteinsson, Viktor A.

Issue&Volume: 2023-04-27

Abstract: Detecting mutations from single DNA molecules is crucial in many fields but challenging. Next-generation sequencing (NGS) affords tremendous throughput but cannot directly sequence double-stranded DNA molecules (‘single duplexes’) to discern the true mutations on both strands. Here we present Concatenating Original Duplex for Error Correction (CODEC), which confers single duplex resolution to NGS. CODEC affords 1,000-fold higher accuracy than NGS, using up to 100-fold fewer reads than duplex sequencing. CODEC revealed mutation frequencies of 2.72×108 in sperm of a 39-year-old individual, and somatic mutations acquired with age in blood cells. CODEC detected genome-wide, clonal hematopoiesis mutations from single DNA molecules, single mutated duplexes from tumor genomes and liquid biopsies, microsatellite instability with 10-fold greater sensitivity and mutational signatures, and specific tumor mutations with up to 100-fold fewer reads. CODEC enables more precise genetic testing and reveals biologically significant mutations, which are commonly obscured by NGS errors.

DOI: 10.1038/s41588-023-01376-0

Source: https://www.nature.com/articles/s41588-023-01376-0

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex