Identification of Novel Biomarkers for Acute Radiation Injury Using Multiomics Approach and Nonhuman Primate Model

Purpose: The availability of validated biomarkers to assess radiation exposure and to assist in developing medical counter-measures remains an unmet need. Methods and Materials: We used a cobalt-60 gamma-irradiated nonhuman primate (NHP) model to delineate a multiomics-based serum probability index of radiation exposure. Both male and female NHPs were irradiated with different doses ranging from 6.0 to 8.5 Gy, with 0.5 Gy increments between doses. We leveraged high-resolution mass spectrometry for analysis of metabolites, lipids, and proteins at 1, 2, and 6 days postirradiation in NHP serum. Results: 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 6 days after exposure. This panel was comprised of Serpin family A9, acetylcarnitine, glycerophosphocholine (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 as a molecular diagnostic for human use after larger validation studies. Conclusions: Taken together, this study, for the first time, demonstrates the utility of a combinatorial molecular characterization approach using an NHP model for developing minimally invasive assays from small volumes of blood that can be effectively used for radiation exposure assessments. Published by Elsevier Inc.

Automated summary

This study developed a multiomics-based serum probability index of radiation exposure using a nonhuman primate model. By analyzing metabolites, lipids, and proteins, a panel was constructed to accurately assess radiation exposure, which can contribute to the development of molecular diagnostic tools for radiation exposure.