New Approaches for Quantitative Reconstruction of Radiation Dose in Human Blood Cells

In the event of a nuclear attack or radiation event, there would be an urgent need for assessing and reconstructing the dose to which hundreds or thousands of individuals were exposed. These measurements would need a rapid assay to facilitate triage and medical management for individuals based on dose. Our approaches to development of rapid assays for reconstructing dose, using transcriptomics, have led to identification of gene sets that have potential to be used in the field; but need further testing. This was a proof-of-principle study for new methods using radiation-responsive genes to generate quantitative, rather than categorical, radiation-dose reconstructions based on a blood sample. We used a new normalization method to reduce effects of variability of gene signals in unirradiated samples across studies; developed a quantitative dose-reconstruction method that is generally under-utilized compared to categorical methods; and combined these to determine a gene-set as a reconstructor. Our dose-reconstruction biomarker was trained on two data sets and tested on two independent ones. It was able to predict dose up to 4.5 Gy with root mean squared error (RMSE) of {+/-} 0.35 Gy on test datasets (same platform), and up to 6.0 Gy with RMSE of 1.74 Gy on another (different platform).