RadiSeq: a single- and bulk-cell whole-genome DNA sequencing simulator for radiation-damaged cell models

Objective.To build and validate a simulation framework to perform single-cell and bulk-cell whole genome sequencing simulation of radiation-exposed Monte Carlo (MC) cell models to assist radiation genomics studies.Approach.Sequencing the genomes of radiation-damaged cells can provide useful insight into radiation action for radiobiology research. However, carrying out post-irradiation sequencing experiments can often be challenging, expensive, and time-consuming. Although computational simulations have the potential to provide solutions to these experimental challenges, and aid in designing optimal experiments, the absence of tools currently limits such application. MC toolkits exist to simulate radiation exposures of cell models but there are no tools to simulate single- and bulk-cell sequencing of cell models containing radiation-damaged DNA. Therefore, we aimed to develop a MC simulation framework to address this gap by designing a tool capable of simulating sequencing processes for radiation-damaged cells. Main results.We developed RadiSeq-a multi-threaded whole-genome DNA sequencing simulator written in C++. RadiSeq can be used to simulate Illumina sequencing of radiation-damaged cell models produced by MC simulations. RadiSeq has been validated through comparative analysis, where simulated data were matched against experimentally obtained data, demonstrating reasonable agreement between the two. Additionally, it comes with numerous features designed to closely resemble actual whole-genome sequencing. RadiSeq is also highly customizable with a single input parameter file.Significance.RadiSeq enables the research community to perform complex simulations of radiation-exposed DNA sequencing, supporting the optimization, planning, and validation of costly and time-intensive radiation biology experiments. This framework provides a powerful tool for advancing radiation genomics research.