Human Health Exposure Analysis Resource Core: Untargeted Analysis

项目摘要/摘要(总体) 暴露于与环境有关的化学品、药物、药物和摄取营养物质，以及 它们如何扰乱内源性新陈代谢与许多类型的不良健康后果有关。 我们的中心拥有资源、熟练的员工和知识，可以立即提供Exposome服务 人类健康暴露分析资源(HHEAR)计划(RFA-ES-18-012)的客户。我们发起了 通过NIH共同基金(C-F)代谢组学的赠款，我们在2012年的非靶向分析核心 计划，并已建立并应用代谢组学方法进行了数百项研究，超过30项 美国各地的组织。这些研究包括对广泛的 与多种类型的健康结果有关的生物菌群(如尿液、血清、血浆、汗液、粪便) 在妇幼健康、肾脏疾病、心血管疾病、肥胖和糖尿病的研究中，以及 对治疗的反应。美国国立卫生研究院C-F东部区域综合代谢组学的成功 资源核心(ERCMRC)导致我们建立了儿童健康暴露分析资源 (CHEAR)中心是NIEHS CHEAR计划的一部分。在CHEAR计划下，我们成功地 执行了我们的目标，其中包括a)扩展我们的服务，以包括对 使用高分辨率Orbitrap质谱学的Exposome，b)建立广泛的内部物理 外源和内源化合物标准库在非目标平台上运行，以及c) 参与实验室间的比较，揭示与环境有关的分析物的范围 在我们的非目标平台上被识别。我们的无目标方法会导致数万个信号 通过匹配公共数据库进行注释，并根据我们的内部物理数据进行注释和识别 标准库，使用大数据分析。我们的核心引领了基于证据的本体论的发展 CHEAR方案的系统，它确保对注释和赋值的信心将是 在集线器之间进行清晰的沟通。我们有100多个经过微调的协议，这些协议跨越整个工作流程 从接收样品到报告数据，并制定了质量控制程序/保证程序 用于工作流程的所有步骤。HHEAR非目标集线器将在HHEAR网络和其他 HHEAR中心、HHEAR数据分析中心(DAC)和HHEAR协调中心(CC) 为非定向分析提供客户服务，并在整个财团内协调和 整合结果。HHEAR中心将在Timothy Fennell博士的多重PI领导计划下领导 (行政核心和发展核心主任)，苏珊·萨姆纳博士(非目标分析主任 资源)和杜秀霞博士(计算展示体工作流程负责人)。我们随时准备为您提供 使用广泛的生物检疫试剂和最新技术进行流行病学调查的非靶向分析 技术和分析方法，以揭示环境对疾病的影响。

Project Summary/Abstract (Overall) Exposures to environmentally relevant chemicals, drugs, medications, and the ingestion of nutrients, and how they perturb endogenous metabolism have been linked with many types of adverse health outcomes. Our Hub has the resources, skilled staff, and knowledge to immediately provide Exposome services to clients of the Human Health Exposure Analysis Resource (HHEAR) Program (RFA-ES-18-012). We initiated our Untargeted Analysis Core in 2012 through a grant from the NIH Common Fund (C-F) Metabolomics Program, and have established and applied metabolomics methods to hundreds of studies with over 30 organizations across the United States. These studies have included analysis of a wide range of biospecimens (e.g., urine, serum, plasma, sweat, feces) with anchors to numerous types of health outcomes in studies of maternal and child health, kidney disease, cardiovascular disease, obesity and diabetes, and response to treatment. The success of the NIH C-F Eastern Regional Comprehensive Metabolomics Resource Core (ERCMRC) led to our establishing a Children's Health Exposure Analysis Resource (CHEAR) Hub as part of the NIEHS CHEAR Program. Under the CHEAR Program, we successfully executed our goals, which included a) expanding our services to include high-throughput analysis of the Exposome using high-resolution Orbitrap mass spectrometry, b) establishing an extensive in-house physical standards library of exogenous and endogenous compounds run on the untargeted platform, and c) participating in cross laboratory comparisons to reveal the range of environmentally relevant analytes identified on our untargeted platform. Our untargeted methods result in tens of thousands of signals that are annotated by matching to public databases, and annotated and identified against our in-house physical standards library, using Big Data Analytics. Our core led the development of an evidence-based Ontology System for the CHEAR Program, which ensures that the confidence in annotations and assignments will be clearly communicated between Hubs. We have in place over 100 fine-tuned protocols that span the workflow from receipt of samples through reporting data, and that have quality control/assurance procedures in place for all steps of the workflow. The HHEAR Untargeted Hub will work within the HHEAR Network and other HHEAR Hubs, the HHEAR Data Analysis Center (DAC), and the HHEAR Coordinating Center (CC) to provide client services for Untargeted Analysis, and to work across the consortium to harmonize and integrate results. The HHEAR Hub will be led under a Multiple PI Leadership Plan by Dr. Timothy Fennell (Director, Administrative Core and the Development Core), Dr. Susan Sumner (Director, Untargeted Analysis Resource), and Dr. Xiuxia Du (leader, Computational Exposome workflow). We are ready to provide untargeted analysis for epidemiology investigations using a wide range of biospecimens and state-of-the-art technologies, and analysis approaches to reveal the influence of the environment on disease.