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

全身照射后数天内全血基因表达可预测哥廷根小型猪的长期生存

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作者:Sunita Chopra, Maria Moroni, Jaleal Sanjak, Laurel MacMillan, Bernadette Hritzo, Shannon Martello, Michelle Bylicky, Jared May, C Norman Coleman, Molykutty J Aryankalayil

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.

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