Spatial Metabolomics for Human Kidneys

人类肾脏空间代谢组学

基本信息

批准号：
10005039
负责人：
Kumar Sharma
金额：
$ 52.98万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10005039
关键词：
3-Dimensional Acute Acute Renal Failure with Renal Papillary Necrosis Anatomy Area Atlases Big Data Bioinformatics Biological Markers Blood California Cells Chronic Chronic Kidney Failure Collaborations Communities Complement Data Data Set Databases Development Diagnostic Disease Disease Progression European Fourier transform ion cyclotron resonance Goals Human Human Resources Image In Situ Individual Injury Institutes Kidney Kidney Diseases Knowledge Laboratories Leadership Maps Mass Spectrum Analysis Metabolic Metabolic Pathway Metabolism Methods Molecular Molecular Biology Morbidity - disease rate Nephrology Normal tissue morphology Pacific Northwest Pathogenesis Pathway interactions Patients Phase Phenotype Preventive Protocols documentation Recovery Resolution Sampling Services Site Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Statistical Data Interpretation Structure Technology Therapeutic Tissue Procurements Tissues Translating Universities Urine base bioinformatics resource design disease heterogeneity disorder subtype graphical user interface high resolution imaging improved industry partner metabolic profile metabolomics mortality multidisciplinary multiple omics next generation novel optical imaging precision medicine prognostic programs reconstruction scale up small molecule ultra high resolution web services

项目摘要

Project Summary / Abstract Acute kidney injury (AKI) and chronic kidney disease (CKD) are major contributors to overall morbidity and mortality in patients in the US. The overall objective of the proposed study is to establish untargeted and targeted spatial metabolomics analysis of tissues from normal and diseased kidneys to assess cellular metabolic states associated with healthy function, acute injury, chronic condition, and recovery. We will employ ultra-high resolving power imaging mass spectrometry (e.g., MALDI-FTICR-IMS) complemented with novel bioinformatics (e.g., METASPACE) for metabolite annotation and big data interrogation strategies to identify alterations of metabolism in diseased kidneys compared with normal ones. Our Tissue Interrogation Site will be a multi-disciplinary coordinated program composed of leadership in translational nephrology and imaging mass spectrometry at UCSD, outstanding facilities for multi-omics analysis at Pacific Northwest National Laboratories (PNNL), and bioinformatics for mass spectrometry imaging and 3-D reconstruction housed at European Molecular Biology Laboratories (EMBL). Three specific aims in each phase (i.e., UG3 and UH3) are proposed. In particular, we will establish an untargeted and targeted spatial metabolomics platforms for human kidney interrogation and develop an open bioinformatics platform for data interrogation, 3-D reconstruction, molecular interpretation and public sharing. In the UH3 phase, the untargeted and targeted platforms will be scaled up to improve metabolite coverage and develop key metabolic pathways for specific renal compartments in kidneys from individuals with AKI, CKD, and disease subgroups. Moreover, the bioinformatics platform will also be scaled up to establish 3D (a next-generation technology) metabolite-based maps of kidney structure in normal and diseased kidneys. A web-service SM-Kidney will be implemented as the online platform to have all the datasets and the results publicly sharable. We will contribute and collaborate with the Central Hub (CH) to integrate our service for the formation of a molecular kidney atlas. With strong collaborations among the key personnel from UCSD, PNNL, EMBL, and other universities, institutes, and industry partners, our multidisciplinary team will reach key milestones during both the UG3 and UH3 phases. Milestones include 1) the development of a comprehensive untargeted database of metabolite annotations in the normal human renal compartments, 2) targeted spatial metabolomics analysis for selected classes of metabolites and pathways, 3) methods and SOPs that meet rigorous QC standards for tissue procurement, initial processing and IMS with optical imaging and 4) providing the online service SM-Kidney with a graphical user interface to evalaute spatial metabolic profiles associated with kidney disease and pathogenesis. All protocols, samples, data, and metabolite atlas of normal, AKI, and CKD samples will be shared across the KPMP.

项目概要/摘要急性肾损伤 (AKI) 和慢性肾病 (CKD) 是总体发病率和死亡率的主要原因美国患者的死亡率。拟议研究的总体目标是建立无针对性的、对正常和患病肾脏组织进行有针对性的空间代谢组学分析，以评估细胞与健康功能、急性损伤、慢性病和恢复相关的代谢状态。我们将聘用超高分辨力成像质谱（例如 MALDI-FTICR-IMS）辅以新颖的用于代谢物注释的生物信息学（例如 METASPACE）和大数据询问策略来识别与正常肾脏相比，患病肾脏的代谢发生变化。我们的组织询问站点将是一个多学科协调项目，由转化肾病学和影像质量领域的领导者组成加州大学圣地亚哥分校 (UCSD) 的光谱测定法、太平洋西北国家大学 (Pacific Northwest National) 的多组学分析杰出设施实验室 (PNNL) 以及用于质谱成像和 3D 重建的生物信息学位于欧洲分子生物学实验室（EMBL）。每个阶段（即 UG3 和 UH3）的三个具体目标是建议的。特别是，我们将为人类建立非靶向和靶向空间代谢组学平台。肾脏询问并开发一个开放的生物信息学平台，用于数据询问、3D 重建、分子解释和公众分享。在UH3阶段，非目标和目标平台将被扩大规模以提高代谢物覆盖率并开发特定肾脏的关键代谢途径来自患有 AKI、CKD 和疾病亚组的个体的肾脏隔室。此外，生物信息学该平台还将扩大规模，以建立基于 3D（下一代技术）的肾脏代谢图正常和患病肾脏的结构。网络服务 SM-Kidney 将作为在线平台实施使所有数据集和结果可公开共享。我们将与中央做出贡献并合作 Hub (CH) 整合我们的服务以形成分子肾脏图谱。凭借强大的合作来自 UCSD、PNNL、EMBL 以及其他大学、研究所和行业合作伙伴的关键人员，我们的多学科团队将在 UG3 和 UH3 阶段达到关键里程碑。里程碑包括 1）开发正常人代谢物注释的综合非靶向数据库肾区室，2) 针对选定类别的代谢物进行有针对性的空间代谢组学分析途径，3) 符合组织采购、初始处理严格 QC 标准的方法和 SOP 和具有光学成像的 IMS，4) 提供带有图形用户界面的在线服务 SM-Kidney 评估与肾脏疾病和发病机制相关的空间代谢特征。所有协议、样本、正常、AKI 和 CKD 样本的数据和代谢图谱将在 KPMP 中共享。