Whole blood gene expression within days after total-body irradiation predicts long term survival in Gottingen minipigs

Sci Rep. 2021 Aug 5;11(1):15873. doi: 10.1038/s41598-021-95120-5.

Abstract

Gottingen minipigs mirror the physiological radiation response observed in humans and hence make an ideal candidate model for studying radiation biodosimetry for both limited-sized and mass casualty incidents. We examined the whole blood gene expression profiles starting one day after total-body irradiation with increasing doses of gamma-rays. The minipigs were monitored for up to 45 days or time to euthanasia necessitated by radiation effects. We successfully identified dose- and time-agnostic (over a 1-7 day period after radiation), survival-predictive gene expression signatures derived using machine-learning algorithms with high sensitivity and specificity. These survival-predictive signatures fare better than an optimally performing dose-differentiating signature or blood cellular profiles. These findings suggest that prediction of survival is a much more useful parameter for making triage, resource-utilization and treatment decisions in a resource-constrained environment compared to predictions of total dose received. It should hopefully be possible to build such classifiers for humans in the future.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Blood Cells / radiation effects*
  • Dose-Response Relationship, Radiation
  • Gamma Rays / adverse effects
  • Gene Expression / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / genetics
  • Prognosis
  • Radiation Injuries / blood
  • Radiation Injuries / genetics
  • Swine
  • Swine, Miniature / blood
  • Swine, Miniature / metabolism
  • Transcriptome / genetics
  • Whole-Body Irradiation / adverse effects*
  • Whole-Body Irradiation / mortality*

Substances

  • Biomarkers