Vanderbilt University Biomolecular Multimodal Imaging Center for 3-Dimensional Mapping of the Human Kidney

范德比尔特大学生物分子多模态成像中心进行人体肾脏 3 维绘图

• 批准号: 10701827
• 负责人: RICHARD M CAPRIOLI
• 金额: $ 221.16万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701827
• 关键词: 3-Dimensional; Academic Medical Centers; Age; Anatomy; Applications Grants; Atlases; Biomedical Research; Cells; Clinical; Clinical Data; Collaborations; Collection; Communities; Cooperative Human Tissue Network; Data; Data Analyses; Data Set; Development; Dimensions; Disease; Ensure; Environment; Eye; Freezing; Funding; Generations; Goals; Health; Histologic; Histology; Human; Human BioMolecular Atlas Program; Image; Imaging technology; Immunofluorescence Microscopy; Infrastructure; International; Ischemia; Kidney; Knowledge; Laboratories; Lipids; Maps; Mass Spectrum Analysis; Medical Imaging; Medical center; Medicine; Microscopy; Mission; Modality; Molecular; Molecular Analysis; Monitor; Multimodal Imaging; National Center for Research Resources; Nephrectomy; Netherlands; Organ; Pancreas; Participant; Performance; Phenotype; Physicians; Positioning Attribute; Procedures; Process; Proteins; Proteomics; Quality Control; RNA; Race; Reproducibility; Research; Research Personnel; Resolution; Resources; Sampling; Scientist; Selection Criteria; Specimen; Stains; Standardization; Surface; System; Techniques; Technology; Testing; Time; Tissue Donors; Tissues; Transcript; Transplantation; United States National Institutes of Health; Universities; Work; biocomputing; body system; cell type; chemical fixation; data integration; demographics; ex vivo imaging; human tissue; imaging facilities; imaging modality; improved; in vivo; innovation; insight; mass spectrometric imaging; member; multidisciplinary; multimodal data; multimodality; novel; preservation; programs; quality assurance; sex; single nucleus RNA-sequencing; single-cell RNA sequencing; tissue mapping; transcriptome sequencing; transcriptomics

PROJECT SUMMARY – Overall This application proposes the continuation of a Tissue Mapping Center (TMC) for the human kidney within the Human BioMolecular Atlas Program (HuBMAP). The mission of the proposed TMC is to build a platform of integrated technologies for imaging and molecular analysis that enables the construction of comprehensive 3- dimensional molecular atlases of the human kidney. This TMC will leverage the unique resources of the Mass Spectrometry Research Center and the National Research Resource for Imaging Mass Spectrometry at Vanderbilt University, the world-class clinical environment of the Vanderbilt University Medical Center, and the advanced biocomputational infrastructure available to the TMC through the Data Analysis Core laboratories at Vanderbilt University and the Delft University of Technology, Netherlands to create a capability to molecularly characterize human tissues in 3-dimensions at a level of understanding unrivaled by current technologies. The innovative aspect of the proposed TMC is the integration of imaging mass spectrometry, highly multiplexed immunofluorescence microscopy, autofluorescence microscopy, stained microscopy, spatial transcriptomics, spatial proteomics, and single-cell RNA-seq to create comprehensive 2-D and 3-D molecular and cellular atlases of the human kidney. Through segmentation and cell type analysis determined by classical markers, we will correlate our molecular and clinical information to the existing knowledge of the kidney to better define the normal phenotypes across a range of diverse samples. The application of this multimodal pipeline to the kidney will provide a new paradigm of understanding the normal state of this organ across multiple dimensions, both molecular (e.g., lipids, metabolites, proteins, and transcripts) and spatial (e.g., whole organs to single cells). As a HuBMAP participant, the molecular atlases produced by this TMC will be disseminated to the community and to collaborators to generate new hypotheses regarding the function of this important organ system, enabling new insight into human health and disease. This multidisciplinary effort requires the creation and integration of three capabilities to 1) procure and manage human tissue specimens, 2) determine and mitigate non-biological pre- analytical factors, and 3) acquire, process, and disseminate multimodal 3-dimensional imaging and large-scale omics data. The goal of the proposed kidney TMC is to create atlases for community users, physicians, and researchers to navigate across the anatomical and molecular landscape of the kidney, generate novel hypotheses, and tackle meaningful biomedical research questions.

项目概要——总体 该申请建议在该中心内继续建立人类肾脏组织绘图中心（TMC） 人类生物分子图谱计划 (HuBMAP)。拟议 TMC 的使命是建立一个平台 成像和分子分析的集成技术，能够构建全面的 3- 人类肾脏的三维分子图谱。该 TMC 将利用大众的独特资源 光谱研究中心和国家成像质谱研究资源 范德比尔特大学、范德比尔特大学医学中心世界一流的临床环境以及 通过数据分析核心实验室，TMC 可以使用先进的生物计算基础设施 范德比尔特大学和荷兰代尔夫特理工大学建立分子生物学能力 以当前技术无法比拟的理解水平对人体组织进行 3 维表征。这 所提出的 TMC 的创新方面是成像质谱、高度多重分析的集成 免疫荧光显微镜、自发荧光显微镜、染色显微镜、空间转录组学、 空间蛋白质组学和单细胞 RNA-seq 创建全面的 2-D 和 3-D 分子和细胞图谱 人类肾脏的。通过经典标记确定的分割和细胞类型分析，我们将 将我们的分子和临床信息与现有的肾脏知识相关联，以更好地定义正常值 一系列不同样本的表型。这种多模式管道在肾脏中的应用将 提供了一种跨多个维度理解该器官正常状态的新范式， 分子（例如脂质、代谢物、蛋白质和转录本）和空间（例如整个器官到单个细胞）。作为 作为 HuBMAP 参与者，该 TMC 制作的分子图谱将向社区传播， 帮助合作者就这一重要器官系统的功能提出新的假设，从而实现新的 对人类健康和疾病的洞察。这种多学科的努力需要创建和整合三个 有能力 1) 采购和管理人体组织样本，2) 确定和减轻非生物预 分析因素，3) 获取、处理和传播多模态 3 维成像和大规模 组学数据。拟议的肾脏 TMC 的目标是为社区用户、医生和患者创建地图集 研究人员探索肾脏的解剖和分子景观，产生新的 假设，并解决有意义的生物医学研究问题。

项目成果

Prospective on Imaging Mass Spectrometry in Clinical Diagnostics.

• DOI: 10.1016/j.mcpro.2023.100576
• 发表时间: 2023-09
• 期刊: MOLECULAR & CELLULAR PROTEOMICS
• 影响因子: 7
• 作者: Moore, Jessica L.;Patterson, Nathan Heath;Norris, Jeremy L.;Caprioli, Richard M.
• 通讯作者: Caprioli, Richard M.