Rapid Low-Cost Paper-based Biodosimetry that reveals individual organ injuries

摘要： 核事故和/或恐怖主义的威胁日益增加，引发了对 确认和量化暴露于核辐射的大量人群的吸收辐射剂量的能力 意外辐射量未知。一种有效的分诊方法有可能节省 成千上万条生命。为了最大限度地利用可用资源，分步分类建议首先 使用护理点(POC)测试来区分未接触者和已接触者 人口，然后使用高通量定量评估那些接触过的人 分析方法估算其吸收的辐射剂量。理想的PoC测试将预测 对主要器官的急性和延迟性辐射损伤，如骨髓。要估计 吸收剂量，生物剂量学测量宿主对电离辐射的生物反应。这个 特定基因的表达会根据辐射剂量的不同而改变。在这里，我们使用表达式 这些辐射反应基因的水平作为暴露于辐射的生物标志物。此前， 我们使用基因组方法结合体内NHP模型来识别许多辐射 并开发一种高通量实验室测试来检测和量化吸收 照射后7天内的辐射剂量。对这些数据的新分析揭示了一个子集 区分接触者和非接触者的生物标记物。此外，其中一个 辐射暴露的特征是淋巴细胞总数迅速下降。这是一项新的 一组生物标志物可以定量地预测7岁时淋巴细胞计数的显著下降 暴露后数天，仅在暴露后24小时。我们也有技术可以将我们的 基因表达分析成为一种低成本的纸质POC测试，与筛查A 人口众多。通过结合我们的能力和目前可用的生物标记物，我们打算 开发一种低成本的POC测试：1)识别暴露在意外辐射中的个人；2) 根据个人吸收的辐射剂量对个人进行定性分类；3)预测风险 通过在第一天计算他们未来的第七天淋巴细胞计数来判断严重的骨髓损伤。我们 将分三步执行我们的项目学习计划。首先，我们将选择最佳子集 通过分析基因表达数据集和整理文献来确定生物标记物。第二，我们将 使我们基于纸质、低成本的POC测试适应这些标记的关键表达水平。 最后，我们将使用独立的未知样本来验证我们的测试和生物标记物。

Abstract: Increasing threats of nuclear accidents and/or terrorism have triggered an urgent need for the ability to confirm and quantify absorbed radiation doses in a large population exposed to an unknown amount of unintended radiation. An effective triage method has the potential to save thousands of lives. To best utilize the available resources, stepwise triage recommends first using a point-of-care (POC) test that distinguishes between the non-exposed and the exposed population, followed by an assessment of those exposed using high throughput quantitative analysis methods to estimate their absorbed doses of radiation. The ideal POC test will predict acute and delayed radiation injuries to major organs, like bone marrow. To estimate the absorbed dose, biodosimetry measures host biological responses to ionizing radiation. The expression of specific genes alters based on the dose of radiation. Here we use the expression levels of these radiation-responsive genes as biomarkers of exposure to radiation. Previously, we used genomic approaches coupled with an in vivo NHP model to identify many radiation responsive genes and develop a high throughput laboratory test to detect and quantify absorbed dose of radiation within 7 days of post exposure. A new analysis of these data reveals a subset of biomarkers that distinguish exposed from non-exposed individuals. Moreover, one of the hallmarks of radiation exposure is a rapid decay in the total number of lymphocytes. This new panel of biomarkers can quantitatively predict a significant drop in the lymphocyte count at 7 days post exposure, only 24 hours post exposure. We also have technology for converting our gene expression assays into a low-cost paper-based POC test, compatible with screening a large population. By combining our capabilities and currently available biomarkers, we intend to develop a low-cost POC test that; 1) identifies individuals exposed to unintended radiation; 2) qualitatively classifies individuals based on their absorbed dose of radiation; 3) predicts the risk of serious bone marrow injury by calculating their future day 7 lymphocyte counts on day 1. We will execute our project study plan in three steps. First, we will select the best subset of biomarkers by analyzing gene expression data sets and curating literature. Second, we will adapt our paper-based, low-cost, POC test to the critical expression levels of these markers. Finally, we will validate our test and biomarkers using independent unknown samples.