Machine learning approach for quantitative biodosimetry of partial-body or total-body radiation exposures by combining radiation-responsive biomarkers

Abstract

During a large-scale radiological event such as an improvised nuclear device detonation, many survivors will be shielded from radiation by environmental objects, and experience only partial-body irradiation (PBI), which has different consequences, compared with total-body irradiation (TBI). In this study, we tested the hypothesis that applying machine learning to a combination of radiation-responsive biomarkers (ACTN1, DDB2, FDXR) and B and T cell counts will quantify and distinguish between PBI and TBI exposures. Adult C57BL/6 mice of both sexes were exposed to 0, 2.0–2.5 or 5.0 Gy of half-body PBI or TBI. The random forest (RF) algorithm trained on ½ of the data reconstructed the radiation dose on the remaining testing portion of the data with mean absolute error of 0.749 Gy and reconstructed the product of dose and exposure status (defined as 1.0 × Dose for TBI and 0.5 × Dose for PBI) with MAE of 0.472 Gy. Among irradiated samples, PBI could be distinguished from TBI: ROC curve AUC = 0.944 (95% CI: 0.844–1.0). Mouse sex did not significantly affect dose reconstruction. These results support the hypothesis that combinations of protein biomarkers and blood cell counts can complement existing methods for biodosimetry of PBI and TBI exposures.

Assessment of Micronuclei Frequency in the Peripheral Blood of Adult and Pediatric Patients Receiving Fractionated Total Body Irradiation

“…This highlights the important need for future prospective population studies to comprehensively assess individual radiosensitivity using validated biomarkers of radiation exposure. In future work, our goal is to build on these patient datasets for dose and time after TBI (and PBI) exposures and use novel machine learning methods developed in our group to combine MN/BN, NDI, and NLR endpoints to more accurately determine the magnitude of cytogenetic DNA damage in peripheral blood T lymphocytes and likelihood of developing hematopoietic injury following radiation exposure [Shuryak et al, 2022[Shuryak et al, , 2023.…”

BAX and DDB2 as biomarkers for acute radiation exposure with in the first week after irradiation in ex-vivo human and nonhuman primate model

“…Early in our research, we identi ed a panel of top-candidate intracellular protein biomarkers (DDB2, BAX, FDXR, TSPYL2 and ACTN1), using shotgun proteomics to assess proteome-wide changes in human CD45 + blood leukocytes in X-irradiated humanized mice [18] . Since then, we have evaluated the performance of the FAST-DOSE bioassay across different models and species including a human blood ex-vivo model [19] , non-human primates (NHP) 13 , and both humanized and C57BL/6 mice [13,20] . The objective of this work was to transition and integrate two of our top-performing biomarkers BAX (BCL2 associated X, a regulator of apoptosis [21,22] ) and DDB2 (DNA damage speci c binding protein, a protein which binds to DNA as part of the cellular response to DNA damage [23] ) into an ELISA-based platform with the goal to simplify the assay to increase speed and reduce the time-to-result.…”

Performance Evaluation of Radiation-Shielding Materials and Process Technology for Manufacturing Skin Protection Cream

“…However, in reality, these aprons are limited in protecting all parts of the human body [4,5]. In particular, imaging operators are virtually defenseless against radiation exposure because they rely on manual techniques and tactile sensations of the hand [6].…”