Identification of multi-omics molecular signature of acute radiation injury using nonhuman primate model

Abstract

The availability of validated biomarkers to assess radiation exposure and to assist in developing medical countermeasures remains an unmet need. We used a cobalt 60 gamma irradiated nonhuman primate model to delineate a multi-omics based serum probability index of radiation exposure. Both male and female NHPs were irradiated with different doses ranging from 6.0 to 8.5 Gray, with 0.5 Gray increments between doses. We leveraged high resolution mass spectrometry for analysis of metabolites, lipids, and proteins at 1, 2, and 6 days post irradiation in NHP serum. A logistic regression model was implemented to develop a 4 analyte panel to stratify irradiated NHPs from unirradiated with high accuracy that was agnostic for all doses of gamma rays tested in the study, up to six days after exposure. This panel was comprised of Serpin Family A9, acetylcarnitine, PC (16:0/22:6), and suberylglycine, which showed 2 to 4 fold elevation in serum abundance upon irradiation in NHPs, and can potentially be translated for human use following larger validation studies. Taken together, this study, for the first time, demonstrates the utility of a combinatorial molecular characterization approach using an nonhuman primate model for developing minimally invasive assays from small volumes of blood that can be effectively used for radiation exposure assessments.