Undiagnosed Diseases Network Metabolomics Core

 描述（由申请人提供）：最先进的代谢组学核心将成为未确诊疾病网络（UDN）的重要组成部分。然而，为了让 UDN 充分发挥潜力，代谢组学核心不能简单地充当高科技转诊实验室。我们建议建立合作伙伴关系，将太平洋西北国家实验室 (PNNL) 最先进的分析能力与俄勒冈健康与科学大学 (OHSU) 的临床、遗传和生物信息学专业知识相结合，创建一个代谢组学核心，作为网络的完全集成组件。这种综合专业知识的整合将促进新代谢物或模式的联系 代谢组学核心鉴定的代谢物与潜在的代谢和遗传紊乱以及临床体征和症状有关，并将这些知识转化为有关患者疾病遗传病因学的具体线索。该代谢组学核心的主要目标是提供代谢组学检测和计算资源，以解决开发利用代谢组学诊断疾病的现代方法所面临的巨大挑战。为了实现这些目标，我们将与 UDN 中心互动，为代谢组学实验设计、样品收集和存储、样品分析以及数据处理和分析的各个方面提供指导。我们将进行全面、定量的非靶向和靶向测量，以确定与罕见和未确诊疾病相关的分子谱变化，同时提供与未确诊疾病相关的新型代谢物的结构测定。我们将与 UDN 中心（包括治疗医生）密切合作，将代谢组学和基因组学数据与患者临床表型相结合，以帮助诊断并为罕见和未确诊疾病提供机制见解。这项工作意义重大，因为它将最先进的代谢组学、脂质组学和糖组学测量应用于罕见和未确诊疾病的研究。这项工作具有创新性，因为它将 PNNL 团队在质谱和组学测量方面的集体专业知识与 OHSU 团队在遗传性代谢疾病和深度语义表型分析方面的专业知识相结合，并将其应用于疾病诊断的挑战。

 DESCRIPTION (provided by applicant): A state of the art metabolomics core will be a vital part of the Undiagnosed Diseases Network (UDN). However, in order for the UDN to realize it's the full potential it is essential that the metabolomics core doesn't simply function as a high tec referral lab. We propose the formation of a partnership that will combine the state of the art analytical capabilities of the Pacific Northwest National Laboratory (PNNL), with clinical, genetic and bioinformatics expertise from Oregon Health & Science University (OHSU), to create a metabolomics core that functions as a fully integrated component of the network. The integration of this combined expertise will facilitate the linkage of novel metabolites or patterns of metabolites identified by the metabolomics core to the underlying metabolic and genetic derangements, as well as clinical signs and symptoms, and to translate this knowledge into specific clues regarding the genetic etiology of the patient's disorder. The major goal of this metabolomics core is to provide metabolomics assays and computational resources that will address the enormous challenges in developing a modern approach to the use of metabolomics in the diagnosis of disease. To achieve these objectives, we will interact with the UDN Centers to provide guidance on all aspects of metabolomics experimental design, sample collection and storage, sample analysis, and data processing and analysis. We will perform comprehensive, quantitative untargeted and targeted measurements to identify changes in molecular profiles that are associated with rare and undiagnosed diseases, while providing structural determination of novel metabolites associated with undiagnosed diseases. Working closely with the UDN Centers, including the treating physicians, we will integrate metabolomics and genomics data with patient clinical phenotypes to both aid diagnosis and provide mechanistic insight for rare and undiagnosed diseases. This work is significant because it applies state-of-the- art and advanced metabolomics, lipidomics, and glycomics measurements in the study of rare and undiagnosed diseases. This work is innovative because it combines the collective expertise in mass spectrometry and omics measurements of the PNNL team with the expertise in inherited metabolic disease and deep semantic phenotyping of the OHSU team and applies it to the challenge of diagnosis of disease.