Mayo Clinic Undiagnosed Disease Network Metabolomics Core

项目摘要 该提案将现有的分析资源与马约诊所的临床专业知识结合起来， UDN在罕见病诊断和机制理解中的作用。总体目标是应用国家- 最先进的非靶向和靶向/定量代谢组学方法、生物信息学和专家临床 在已建立的UDN管道内收集的生物样本的解释。的具体目标 马约诊所UDN代谢组学核心是：1）与其他UDN中心合作，2）在全球范围内， 非靶向代谢物分析，3）对选定代谢物进行靶向定量分析，4）提供 检测开发能力，5）为UDN提供临床专业知识，以及6）提供访问我们的 不断壮大的代谢组学专家全国网络。我们的非靶向代谢物分析方法涉及3 通过GC-MS，LC-MS/MS， 和核磁共振光谱。我们有针对性的量化方法将包括关键优先目标（即，聚糖， 脂质和线粒体代谢物）以及广泛的其他靶向代谢物， 在个案基础上提供重要的代谢见解。为了实现这些目标，我们团结了一个多元化的群体， 分析化学家，生理学家，生物信息学家和临床医生作为一个单一的，综合的核心， 为UDN贡献当前的业务工作流程和专业知识。

PROJECT SUMMARY This proposal pairs existing analytical resources with clinical expertise at Mayo Clinic toward the goal of aiding the UDN in the diagnosis and mechanistic understanding of rare diseases. The overall goal is to apply state- of-the-art untargeted and targeted/quantitative metabolomics approaches, bioinformatics, and expert clinical interpretation to the biological samples collected within the established UDN pipeline. The specific aims of the Mayo Clinic UDN Metabolomics Core are: 1) to collaborate with other UDN centers, 2) to perform global, untargeted metabolite profiling, 3) to perform targeted quantitative analysis of select metabolites, 4) to provide assay development capabilities, 5) to provide clinical expertise to the UDN, and 6) to provide access to our growing national network of metabolomics experts. Our approach to untargeted metabolite profiling involves 3 complementary analytical platforms for optimal coverage and annotation of metabolites by GC-MS, LC-MS/MS, and NMR spectroscopy. Our targeted quantitative approach will include key priority targets (i.e., glycans, lipids, and mitochondrial metabolites) as well as a wide breadth of other targetable metabolites that will provide crucial metabolic insights on a case-by-case basis. To accomplish these goals, we unite a diverse group of analytical chemists, physiologists, bioinformaticians, and clinicians as a single, integrated core that is prepared to contribute currently operational workflows and expertise to the UDN.