Rapid High-Throughput Diagnostic Triage after a Mass Radiation Exposure Event Using Early Gene Expression Changes

Area of Science:

• Radiation biology
• Molecular toxicology
• Genomics and transcriptomics

Background:

• Rapid identification of radiation-exposed individuals is crucial for managing mass casualty events.
• Hematological acute radiation syndrome (HARS) severity dictates clinical management and prognosis.
• Previous work identified gene expression signatures for discriminating radiation exposure levels.

Purpose of the Study:

• To evaluate the speed and accuracy of targeted next-generation sequencing (NGS) for classifying radiation exposure.
• To assess the utility of specific gene expression changes in predicting HARS severity.
• To establish a high-throughput biodosimetry method for large-scale radiological incidents.

Main Methods:

• Peripheral blood samples from two healthy donors were irradiated in vitro and incubated for 24 hours.
• A total of 1,000 split blood samples were analyzed using targeted NGS (TREX) for four key genes (FDXR, DDB2, POU2AF1, WNT3).
• Gene expression changes were correlated with HARS severity scores (H0, H1, H2-4) corresponding to 0 Gy, 0.5 Gy, and 5 Gy radiation doses.

Main Results:

• Targeted NGS processed all 1,000 samples within 30 hours, demonstrating high throughput.
• Classification of HARS severity and corresponding radiation doses achieved 90-97% agreement.
• A small set of genes, particularly FDXR, provided robust predictive values for HARS categories and radiation doses.

Conclusions:

• Targeted NGS offers a rapid and efficient method for high-throughput biodosimetry.
• Gene expression analysis of a limited gene set can accurately predict radiation exposure levels and HARS severity.
• This approach supports the rapid identification of individuals needing medical intervention after radiological events.