Single-cell DNA sequencing—a potential dosimetric tool.

This article focuses on investigating the potential of single-cell whole-genome DNA sequencing to detect dose-dependent mutational effects in human cells exposed to ionising radiation (IR). Using a Monte Carlo simulation with a custom geometric nuclear DNA model in TOPAS-nBio, the study predicted a linear increase in complex double-strand break (DSB) clusters per cell with increasing radiation dose. Complementary in vitro experiments irradiated human B-lymphoblastoid cells with photons and analyzed approximately 600 individual cells via single-cell whole-genome sequencing, revealing a comparable dose-dependent increase in copy number losses per cell. Although the simulation and experimental conditions differed and the parameters measured were not directly equivalent, the preliminary results suggest that single-cell sequencing can sensitively capture radiation-induced genomic alterations, offering an alternative approach to studying radiation-associated mutational signatures beyond tumor sample analysis.