Assessment of in vivo chemical mutagenesis by long-read sequencing.

This article focuses on evaluating the use of PacBio-based HiFi sequencing (HiFi seq), a long-read DNA sequencing technology with integrated error correction, to detect de novo mutations induced by chemical mutagens in tissues of C57BL/6 mice. The study demonstrates that HiFi seq can identify dose-dependent increases in mutation frequencies across multiple tissues exposed to known mutagens—7,12-dimethylbenz[a]anthracene (DMBA), procarbazine (PCZ), and N-propyl-N-nitrosourea (PNU)—and that the resulting mutational signatures align with those previously reported for these chemicals. The approach leverages the genetic homogeneity of the inbred mouse strain to distinguish de novo mutations from pre-existing variants, offering a streamlined alternative to Illumina-based error-corrected sequencing methods that require complex library preparations and bioinformatics. The findings suggest that HiFi seq can complement established assays for assessing chemical mutagenicity in animal models, particularly in genetically uniform populations.