Organ-specific Biodosimetry Modeling Using Proteomic Biomarkers of Radiation Exposure

Area of Science:

• Proteomics
• Biomarker Discovery
• Radiation Biology

Background:

• Effective medical management of radiation injury requires accurate diagnostics to identify exposed individuals and assess exposure levels.
• Heterogeneous exposures in mass casualty scenarios necessitate methods to determine the degree of exposure and affected vital organs.

Purpose of the Study:

• To characterize novel proteomic biomarkers for radiation exposure.
• To develop predictive algorithms for radiation exposure and dose estimation.
• To differentiate between total-body and organ-specific (brain, gut, lung) radiation exposures.

Main Methods:

• C57BL6 female mice were subjected to various total-body irradiation (TBI) and organ-specific partial-body exposures.
• Plasma samples were analyzed using the SomaScan v4.1 assay to screen approximately 7,000 protein analytes.
• A subset of radiation-responsive protein biomarkers was identified, and predictive models were built and validated.

Main Results:

• Predictive models achieved high accuracy, with overall accuracy reaching 95.4% for differentiating exposure types (control, TBI, partial-body).
• Models for identifying organ-specific exposures demonstrated accuracies of 78.3% (brain), 88.9% (gut), and 94.4% (lung).
• Models distinguishing between TBI and specific partial-body exposures achieved accuracies up to 92.3%.

Conclusions:

• Novel predictive panels of radiation-responsive proteomic biomarkers were identified.
• The study demonstrates the feasibility of developing biodosimetry algorithms for classifying various radiation exposure scenarios.
• These algorithms have potential utility for simultaneous classification of total-body, partial-body, and organ-specific radiation exposures in clinical settings.