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Multimodal Imaging Mass Spectrometry and Spatial Omics for the Human Kidney

人类肾脏的多模态成像质谱和空间组学

基本信息

批准号：
10701835
负责人：
Jeffrey M Spraggins
金额：
$ 61.25万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-15 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10701835
关键词：
Academic Medical Centers Acute Renal Failure with Renal Papillary Necrosis Affect Age Analytical Chemistry Anatomy Atlases Automobile Driving Biological Biopsy Blood capillaries Cells Cellular biology Characteristics Chronic Kidney Failure Clinical Collection Computer Analysis Data Data Analyses Data Science Data Set Digestion Disease Distal Duct (organ) structure Elements Environment Filtration Heterogeneity Homeostasis Human Human BioMolecular Atlas Program Image Image Analysis Individual Infrastructure Kidney Kidney Diseases Knowledge Label Laboratories Learning Link Lipids Lymphatic Maps Mass Spectrum Analysis Messenger RNA Microscopy Mission Modality Molecular Molecular Analysis Molecular Profiling Morphology Multimodal Imaging Neighborhoods Nephrology Nephrons Pathology Pathway interactions Patients Performance Process Proteins Proteomics Protocols documentation Race Research Research Personnel Resolution Resources Sampling Site Sodium Chloride Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Stains Structure Surface Technology Therapeutic Intervention Tissue atlas Tissues Translating Tubular formation Universities Validation Water analysis pipeline biocomputing blood pressure control cell type clinical phenotype cohort computerized tools data integration digital disease heterogeneity disorder subtype experience experimental study extracellular human imaging image registration imaging Segmentation imaging facilities injured innovation insight interstitial kidney biopsy kidney cell kidney imaging laser capture microdissection mass spectrometric imaging molecular imaging multimodal data multimodality multiple omics nano-string next generation sequencing patient population potential biomarker precision medicine sex spatial integration spatial relationship specific biomarkers supervised learning transcriptomics unsupervised learning

项目摘要

PROJECT SUMMARY: The mission of the proposed Kidney Precision Medicine Project Tissue Interrogation Site (TIS) is to apply a platform of integrated multiomic imaging and spatially resolved molecular technologies to biopsies from patients with acute kidney injury (AKI) and chronic kidney disease (CKD) to define key pathways and understand the molecular drivers of disease heterogeneity. This TIS will leverage the unique resources of the Mass Spectrometry Research Center and VU Biomolecular Imaging Center, as well as the world-class clinical environment of the Vanderbilt University Medical Center, the valuable input of our patient partner, and the advanced biocomputational infrastructure available through the data analysis laboratories at Vanderbilt University and the Delft University of Technology. The main objectives of our TIS are to: (1) generate high quality images of kidney biopsies using an innovative state-of-the-art multimodal imaging pipeline that includes matrix- assisted laser desorption/ionization imaging mass spectrometry (IMS), autofluorescence, and stained microscopy; (2) acquire spatially resolved proteomics and transcriptomics data using microLESA, laser capture microdissection, and the GeoMx Digital Spatial Profiler as well as perform network and enrichment analysis to validate and enhance biological interpretation of the imaging data; and (3) implement advanced data analysis strategies to identify potential biomarkers and optimal points of therapeutic intervention. With this suite of technologies, data analysis capabilities, and previous experience developing atlases of healthy-for-age human kidney tissue, we will create kidney tissue atlases to define the molecular landscape of biopsies from various patient populations (e.g., age, race, sex) as well as of AKI and CKD clinical phenotypes, disease states, and transitions; with an eye toward determining potential disease subclasses. To accomplish these aims, we assembled a highly interactive and established team of investigators consisting of complementary expertise in nephrology, cell biology, analytical chemistry, and data science.

项目摘要：拟议的肾脏精准医学项目组织审讯的使命 Site（TIS）是应用集成多组学成像和空间分辨分子技术的平台对急性肾损伤 (AKI) 和慢性肾病 (CKD) 患者进行活检以确定关键途径并了解疾病异质性的分子驱动因素。该TIS将利用独特的资源质谱研究中心和VU生物分子成像中心，以及世界一流的临床范德比尔特大学医学中心的环境、我们患者合作伙伴的宝贵意见以及范德堡大学数据分析实验室提供先进的生物计算基础设施大学和代尔夫特理工大学。我们 TIS 的主要目标是： (1) 产生高质量使用创新的最先进的多模态成像管道（包括矩阵- 辅助激光解吸/电离成像质谱 (IMS)、自发荧光和染色显微镜检查； (2) 使用 microLESA、激光捕获获取空间分辨的蛋白质组学和转录组学数据显微解剖和 GeoMx 数字空间分析器以及执行网络和富集分析验证并增强成像数据的生物学解释； (3) 实施高级数据分析确定潜在生物标志物和治疗干预最佳点的策略。有了这套技术、数据分析能力以及以前开发健康适龄人类图谱的经验肾组织，我们将创建肾组织图谱来定义来自各种组织的活检的分子景观患者群体（例如年龄、种族、性别）以及 AKI 和 CKD 临床表型、疾病状态和过渡；着眼于确定潜在的疾病亚类。为了实现这些目标，我们组建了一个高度互动且成熟的研究团队，由互补的专业知识组成肾脏病学、细胞生物学、分析化学和数据科学。