Human Health Exposure Analysis Resource Core: Untargeted Analysis

人类健康暴露分析资源核心：非目标分析

• 批准号: 9814480
• 负责人: Xiuxia Du
• 金额: $ 200万
• 依托单位: RESEARCH TRIANGLE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-05 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9814480
• 关键词: Acetaminophen; Amines; Amino Acids; Aromatic Polycyclic Hydrocarbons; Big Data Methods; Biological; Carboxylic Acids; Cardiovascular Diseases; Chemicals; Child Health; Client; Communication; Coupled; Data; Data Analyses; Data Reporting; Databases; Detection; Development; Diabetes Mellitus; Disease; Ensure; Environment; Environmental Exposure; Environmental Health; Epidemiology; Exposure to; Fatty Acids; Feces; Food; Funding; Gas Chromatography; Goals; Grant; Health; Heroin; Human; Infrastructure; Ingestion; Intervention; Investigation; Kidney Diseases; Knowledge; Laboratories; Leadership; Libraries; Link; Liquid Chromatography; Lysophospholipids; Mass Spectrum Analysis; Maternal and Child Health; Measures; Metabolic; Metabolism; Metformin; Methods; Modeling; Morphine; National Institute of Environmental Health Sciences; Nuclear Magnetic Resonance; Nucleosides; Nutrient; Obesity; Ontology; Opioid; Outcome; Parabens; Pesticides; Pharmaceutical Preparations; Phenols; Phenotype; Plasma; Procedures; Process; Protocols documentation; Publications; Quality Control; Reporting; Reproducibility; Research; Resolution; Resources; Running; Sampling; Serum; Services; Signal Transduction; Sweat; System; Technology; Time; Translating; United States; United States National Institutes of Health; Urine; Work; acylcarnitine; case control; cohort; comparative; data resource; drug of abuse; evidence base; experience; high throughput analysis; improved; inorganic phosphate; ion mobility; metabolic phenotype; metabolomics; metabolomics resource; multiple reaction monitoring; outreach; phthalates; polyphenol; programs; quality assurance; response; sample collection; success; sugar; therapy development; time of flight mass spectrometry; tobacco products; treatment response; volatile organic compound

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.

项目概要/摘要（总体） 暴露于与环境相关的化学品、药物、药物和摄入营养物质，以及 它们如何干扰内源性代谢与许多类型的不良健康结果有关。 我们的中心拥有资源，熟练的员工和知识，可以立即为Exposome提供服务， 人类健康暴露分析资源（HHEAR）计划（RFA-ES-18-012）的客户。我们发起 2012年，我们通过NIH共同基金（C-F）代谢组学的资助， 程序，并已建立和应用代谢组学方法，以数百项研究，超过30 美国各地的组织。这些研究包括对广泛的 生物样本（例如，尿液、血清、血浆、汗液、粪便）与多种类型的健康结果相关联 在孕产妇和儿童健康、肾脏疾病、心血管疾病、肥胖症和糖尿病的研究中， 对治疗反应。NIH 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 （CHEMICAL）作为NIEHS CHEMICAL计划的一部分。在CHEMICAL计划下，我们成功地 执行我们的目标，其中包括a）扩大我们的服务，包括高通量分析， B）使用高分辨率Orbitrap质谱法对暴露体进行分析， 在非靶向平台上运行的外源性和内源性化合物的标准品库，以及c） 参与跨实验室比较，以揭示环境相关分析物的范围 在我们的非目标平台上识别。我们的非靶向方法导致成千上万的信号， 通过与公共数据库匹配进行注释，并根据我们的内部物理 标准库，使用大数据分析。我们的核心领导了基于证据的本体论的发展 CHEMICAL计划的系统，它确保注释和作业的信心将 在枢纽之间进行了明确的沟通。我们有超过100个微调的协议，跨越工作流程 从接收样品到报告数据，并已制定质量控制/保证程序 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）， 为非目标分析提供客户服务，并在整个联盟内协调和 综合成果。HHEAR中心将由Timothy Fennell博士在多PI领导计划下领导 （行政核心和发展核心主任），Susan Sumner博士（非目标分析主任 资源）和杜秀霞博士（计算暴露体工作流程负责人）。我们准备提供 使用广泛的生物标本和最先进的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。