评估化学品的致突变特性对于了解其潜在的癌症风险至关重要。最近基于 Illumina 的纠错测序技术已经能够直接检测诱变剂从头诱导的突变。然而，由于 Illumina 平台缺乏内在的纠错能力，因此需要复杂的文库制备和生物信息学过程来识别这些罕见突变。在本研究中，我们评估了基于 PacBio 的长读长 HiFi 测序 (HiFi seq)（集成了纠错功能）是否可以检测 C57BL/6 小鼠组织中诱变剂诱导的从头突变。使用 HiFi seq，在暴露于 7,12-二甲基苯并[a]蒽、丙卡巴肼和 N-丙基-N-亚硝基脲的小鼠组织中发现突变频率呈剂量依赖性增加。此外，从这些暴露中得出的突变特征与之前报道的这些诱变剂的突变特征一致。这项研究表明 HiFi seq 可以补充已建立的突变检测分析，以促进有害化合物的识别。由牛津大学出版社 2024 年出版。

Evaluating the mutagenic properties of chemicals is crucial for understanding their potential cancer risks. Recent Illumina-based error-corrected sequencing techniques have enabled the direct detection of mutations induced de novo by mutagens. However, as the Illumina platform lacks intrinsic error-correction capabilities, complex library preparations and bioinformatic processes are necessary to identify these rare mutations. In this study, we evaluated whether long-read PacBio-based HiFi sequencing (HiFi seq), which has integrated error-correction, can detect de novo mutations induced by mutagens in C57BL/6 mouse tissues. Using HiFi seq, dose-dependent increases in mutation frequencies were found in tissues from mice exposed to 7,12-dimethylbenz[a]anthracene, procarbazine, and N-propyl-N-nitrosourea. Furthermore, the mutational signatures derived from these exposures were consistent with those previously reported for these mutagens. This study demonstrates that HiFi seq can complement established mutation detection assays to facilitate the identification of hazardous compounds.Published by Oxford University Press 2024.