Are radiosensitive and regular response cells homogeneous in their correlations between copy number state and surviving fraction after irradiation?

Biomarkers of radiosensitivity are currently a widespread research interest due to a demand for a sufficient method of prediction of cell response to ionizing radiation. Copy Number State (CNS) alterations may significantly influence individual radiosensitivity. However, their possible impact has not been entirely investigated yet. The purpose of this research was to select markers for which CNS change is significantly associated with the surviving fraction after irradiation with 2 Gy dose (SF2), which is a commonly used measure of cellular radiosensitivity. Moreover, a new strategy of combining qualitative and quantitative approaches is proposed as the identification of potential biomarkers is based not only on the overall SF2 and CNS correlation, but also on differences of it between radiosensitive and regular response cell strains. Four patterns of association are considered and functional analysis and Gene Ontology enrichment analysis of obtained sets of genomic positions are performed. Proposed strategy provides a comprehensive insight into the strength and direction of association between CNS and cellular radiosensitivity. Obtained results suggest that commonly used approach of group comparison based on testing two samples against each other is not sufficient in terms of radiosensitivity since this is not a discrete variable and division into sensitive, normal and resistant individuals is always stipulated.