Biomarker integration for improved biodosimetry of mixed neutron + photon exposures

Abstract

There is a persistent risk of a large-scale malicious or accidental exposure to ionizing radiation that may affect a large number of people. Exposure will consist of both a photon and neutron component, which will vary in magnitude between individuals and is likely to have profound impacts on radiation-induced diseases. To mitigate these potential disasters, there exists a need for novel biodosimetry approaches that can estimate the radiation dose absorbed by each person based on biofluid samples, and predict delayed effects. Integration of several radiation-responsive biomarker types (transcripts, metabolites, blood cell counts) by machine learning (ML) can improve biodosimetry. Here we integrated data from mice exposed to various neutron + photon mixtures, total 3 Gy dose, using multiple ML algorithms to select the strongest biomarker combinations and reconstruct radiation exposure magnitude and composition. We obtained promising results, such as receiver operating characteristic curve area of 0.904 (95% CI: 0.821, 0.969) for classifying samples exposed to ≥ 10% neutrons vs. < 10% neutrons, and R2 of 0.964 for reconstructing photon-equivalent dose (weighted by neutron relative biological effectiveness) for neutron + photon mixtures. These findings demonstrate the potential of combining various -omic biomarkers for novel biodosimetry.