Radiation Biodosimetry Using Gene Expression Signatures

迄今为止，我们的研究为应用基因表达生物剂量学奠定了基础，重点是 用于全身高剂量率外部光子照射的特征显影。其它类型的辐射 暴露，包括部分身体暴露、内部发射体、低剂量率和中子暴露，也将 影响分诊需要，并可能产生不同的反应，或剂量测定签名的变化， 鉴定由于剂量估计值仅提供了一个总体概念， 人口，开发可以提供更准确预测的特征也很重要。 辐射损伤的反应和结果在个人的基础上。 项目2将使用功能基因组学方法开发精细的基因表达特征， 辐射照射和剂量的更新主要涉及两个主题：第一，不同辐射的影响 形式（部分身体暴露、内部发射器、低剂量率和中子暴露），以及第二， 预测个体辐射敏感性。微阵列分析将应用于人类和小鼠 样本，以建立在预测签名，我们已经开发了在第一个资助期的赠款 并使其更好地适应现实的辐射暴露场景。小鼠模型也将用于 研究预测辐射剂量的基因表达特征的机制基础， 灵敏度 项目2将通过辐照核心（核心C）与项目1和项目3紧密结合， 信息学核心（核心E），并通过样本共享的方法，使用人类血液辐照前 体内和体内辐照小鼠。这种示例共享方法还将有助于支持 综合分析方法的核心，涵盖所有三个项目，并使用来自 microRNA、mRNA、代谢组学和细胞水平。这种综合办法将有助于提供 对转录组学和代谢组学特征基础的机械见解，以及 建议高通量生物剂量测定法的最佳组合，以应用于特定的实际应用中， 场景

Our studies to date have laid the groundwork for applied gene expression biodosimetry, focusing on signature development for whole-body high dose rate external photon exposure. Other types of radiation exposures, including partial-body exposure, internal emitters, low dose rate, and neutron exposure, will also impact triage needs, and may produce distinct responses, or variations in the dosimetric signatures already identified. As estimates of dose provide only a general idea ofthe radiation injury expected across a population, it will also be important to develop signatures that may provide a more accurate prediction of radiation injury response and outcome on an individual basis. Project 2 will use a functional genomics approach to develop refined gene expression signatures of radiation exposure and dose addressing the two main renewal themes: first, the impact of different radiation modalities (partial-body exposure, internal emitters, low dose rate, and neutron exposure), and second, prediction of individual radiation sensitivity. Microarray analysis will be applied to human and murine samples to build upon the predictive signatures we have developed in the first funding period of this grant and to better adapt them to realistic radiation exposure scenarios. Mouse models will also be used to nvestigate the mechanistic underpinnings ofthe gene expression signatures that predict radiation dose and sensitivity. Project 2 will be tightly integrated with Projects 1 and 3 through the Irradiation Core (Core C), the Informatics Core (Core E), and through a sample sharing approach using both human blood irradiated ex vivo and in vivo irradiated mice. This sample sharing approach will also help to enable development by the Informatics Core of integrative analysis approaches spanning all three Projects and using data from the microRNA, mRNA, metabolomic, and cellular levels. Such an integrative approach will help provide mechanistic insight into the underpinnings of both transcriptomic and metabolomic signatures, as well as suggesting the best combinations of high-throughput biodosimetry assays to apply in specific practical scenarios.