Abstract：
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.
摘要：
评估化学品的诱变特性对于了解其潜在的癌症风险至关重要。最近基于Illumina的错误校正测序技术已经使得能够直接检测由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，复杂的文库制备和生物信息学过程对于鉴定这些罕见的突变是必要的。在这项研究中,我们评估了基于PacBio的长读数HiFi测序（HiFiseq），集成了纠错，可以检测到C57BL/6小鼠组织中诱变剂诱导的从头突变。使用HiFiseq，在暴露于7,12-二甲基苯并[a]蒽的小鼠组织中发现了突变频率的剂量依赖性增加，丙卡巴嗪,和N-丙基-N-亚硝基脲。此外，来自这些暴露的突变特征与先前报道的这些诱变剂的突变特征一致。这项研究表明，HiFiseq可以补充已建立的突变检测试验，以促进危险化合物的鉴定。
