Gene Expression Signatures That Predict Radiation Exposure in Mice and Humans

BackgroundThe capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation. Methods and FindingsWe have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, ranging from 50 cGy to 1,000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from nonirradiated samples with an accuracy of 90%, sensitivity of 85%, and specificity of 94%. We further demonstrate that a radiation profile developed in the mouse can correctly distinguish PB samples from irradiated and nonirradiated human patients with an accuracy of 77%, sensitivity of 82%, and specificity of 75%. Taken together, these data demonstrate that molecular profiles can be generated that are highly predictive of different levels of radiation exposure in mice and humans. ConclusionsWe suggest that this approach, with additional refinement, could provide a method to assess the effects of various environmental inputs into biological phenotypes as well as providing a more practical application of a rapid molecular screening test for the diagnosis of radiation exposure.背景 精准定量测定环境因素对生物表型贡献的能力，目前受限于现有技术手段，电离辐射暴露领域便是典型一例。 方法与结果 本研究通过对外周血（PB）单个核细胞的基因表达分析，构建可精准反映既往辐射暴露情况的表达谱。研究证实，所构建的表达谱不仅能够预测小鼠的辐射暴露情况，还可区分50 cGy至1000 cGy的辐射暴露等级。同样，仅基于受照人类患者样本构建的辐射应答分子特征，可准确区分受照与未受照的人类外周血样本，准确率达90%、灵敏度85%、特异度94%。本研究进一步表明，在小鼠中构建的辐射特征谱，能够正确区分受照与未受照人类患者的外周血样本，准确率达77%、灵敏度82%、特异度75%。综合上述数据可知，可构建分子特征谱以精准预测小鼠与人类的不同等级辐射暴露水平。 结论 本研究提示，该方法经进一步优化后，既可用于评估各类环境因素对生物表型的影响，也可为辐射暴露诊断提供更实用的快速分子筛查手段。