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

快速低成本纸基生物剂量测定可揭示个体器官损伤

• 批准号: 10092103
• 负责人: JOSHUA LABAER
• 金额: $ 53.93万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10092103
• 关键词: Acute; Address; Affect; Animals; Arizona; Biological; Biological Markers; Biological Models; Blood; Bone Marrow; Categories; Cells; Collaborations; Collection; Coupled; Data Analyses; Data Set; Development; Devices; Diagnostic tests; Dose; Drops; Ensure; Exposure to; Future; Gene Chips; Gene Expression; Gene Expression Profiling; Genes; Genetic Transcription; Genomic approach; Health Personnel; Hour; Human; Individual; Injury; Ionizing radiation; Laboratories; Literature; Lymphocyte; Lymphocyte Count; Lymphocyte Depletion; Measures; Medical; Methods; Modeling; Mus; Normal Range; Nuclear Accidents; Nucleic Acid Amplification Tests; Organ; Paper; Patients; Population; Probability; RNA; Radiation; Radiation Accidents; Radiation Dose Unit; Radiation Injuries; Radiation Tolerance; Radiation exposure; Radiation-Induced Gene Expression; Resources; Risk; Sampling; Specificity; Techniques; Technology; Terrorism; Testing; Therapeutic Intervention; Time; Tissues; Triage; Universities; Work; Zika Virus; base; biodosimetry; biomarker panel; classification algorithm; cohort; cost; design; experience; human model; improved; in vivo; in vivo Model; next generation sequencing; novel strategies; organ injury; peripheral blood; personalized diagnostics; point of care; point of care testing; population based; predictive marker; radiation absorbed dose; response; screening; specific biomarkers; tool

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.

抽象的： 核事故和/或恐怖主义的威胁日益增加，迫切需要 能够确认和量化暴露于辐射的大量人群中吸收的辐射剂量 未知数量的意外辐射。有效的分诊方法有可能节省 成千上万的生命。为了最好地利用可用资源，首先建议逐步分类 使用区分非暴露和暴露的即时护理 (POC) 测试 人口，然后使用高通量定量评估暴露人群 分析方法来估计其吸收的辐射剂量。理想的 POC 测试将预测 对骨髓等主要器官的急性和迟发性辐射损伤。来估计 吸收剂量，生物剂量测定法测量宿主对电离辐射的生物反应。这 特定基因的表达根据辐射剂量而改变。这里我们使用表达式 这些辐射响应基因的水平作为辐射暴露的生物标志物。之前， 我们使用基因组方法结合体内 NHP 模型来识别许多辐射 响应基因并开发高通量实验室测试来检测和量化吸收 暴露后 7 天内的辐射剂量。对这些数据的新分析揭示了一个子集 区分暴露个体和非暴露个体的生物标志物。此外，其中之一 辐射暴露的标志是淋巴细胞总数迅速下降。这个新的 一组生物标志物可以定量预测 7 时淋巴细胞计数的显着下降 暴露后几天，仅暴露后 24 小时。我们还拥有转换我们的技术 将基因表达测定转化为低成本纸质 POC 测试，与筛选 人口众多。通过结合我们的能力和当前可用的生物标志物，我们打算 开发一种低成本的 POC 测试； 1) 识别暴露于意外辐射的个人； 2） 根据吸收的辐射剂量对个体进行定性分类； 3）预测风险 通过计算他们未来第 7 天第一天的淋巴细胞计数来评估严重骨髓损伤。我们 将分三步执行我们的项目研究计划。首先，我们将选择最好的子集 通过分析基因表达数据集和整理文献来确定生物标记。其次，我们将 使我们基于纸质的低成本 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验证我们的测试和生物标志物。