Single-cell DNA sequencing-a potential dosimetric tool

Abstract

We hypothesised that single-cell whole-genome sequencing has the potential to detect mutational differences in the genomes of the cells that are irradiated with different doses of radiation and we set out to test our hypothesis using in silico and in vitro experiments. In this manuscript, we present our findings from a Monte Carlo single-cell irradiation simulation performed in TOPAS-nBio using a custom-built geometric nuclear deoxyribonucleic acid (DNA) model, which predicts a significant dose dependence of the number of cluster damages per cell as a function of radiation dose. We also present preliminary experimental results, obtained from single-cell whole-genome DNA sequencing analysis performed on cells irradiated with different doses of radiation, showing promising agreement with the simulation results.