Mass Spectrometry Molecular Imaging and Multi-Omics

项目总结/摘要 Sidney Kimmel综合癌症中心（SKCCC）质谱分子成像和 Multi-Omics（MSMIMO）共享资源（SR）整合了约翰霍普金斯的三个合作机构： 应用成像质谱（AIMS）设施，质谱和蛋白质组学（MSP）设施， 和代谢组MSMIMO SR提供创新的集成多组工作流程，将联合收割机 用于癌细胞和组织的系统生物学分析的组学技术， 用于分子组织成像（空间组学）、代谢组学和蛋白质组学的质谱技术 加速癌症研究的战略。AIMS提供快速基质辅助激光解吸/电离（MALDI） 多种生物分子的成像，包括内源性肽、蛋白质、N-聚糖、脂质、代谢物， 和药物或药物代谢物在癌细胞、球状体、类器官或组织切片中的高空间分辨率 （5微米）。MSP设施提供蛋白质组学标记和无标记策略，包括多维 蛋白质鉴定技术、平行反应监测、串联质量标签和稳定同位素标记 用于鉴定和相对或靶向定量新治疗性蛋白质的细胞培养物中的氨基酸， 修饰或途径，在癌症中失调，并用于跟踪这些目标的相互作用， 信号转导或蛋白质复合物形成的变化。代谢组学单位提供高 组织或液体提取物中极性和非极性代谢物的通量检测和定量。MSMIMO SR服务包括实验设计，组织切片，样品制备，缓冲液交换，蛋白水解， 标记、衍生、色谱、MALDI成像、串联质谱成像、图像 分析，二维纳米流液相色谱串联质谱分析，数据分析和 口译、协助报告结果、培训和向公共资料库提交数据。 生物统计学家和生物信息学家可对空间组学、代谢组学 和蛋白质组学结果。MSMIMO SR提供专有软件和设备的访问和培训 针对希望进行自己分析并提供操作用户研讨会的SKCCC调查人员- 用质谱仪进行检测。MSMIMO SR的创新方法和 工作流程为SKCCC成员提供空间分辨率，以比较代谢组，药物代谢， 脂质组和蛋白质组在肿瘤微环境内的单个细胞或细胞簇中的表达。我们 全面的、高度多重的分子发现平台旨在促进中心成员的 通过揭示驱动肿瘤发生的分子网络进行研究。在本资助期间，63个SKCCC 研究者使用了MSMIMO SR，有30多篇手稿归因于该SR。 SKCCC托管共享资源 报告期：2020年1月1日至2020年12月31日

PROJECT SUMMARY/ABSTRACT The Sidney Kimmel Comprehensive Cancer Center (SKCCC) Mass Spectrometry Molecular Imaging and Multi-Omics (MSMIMO) Shared Resource (SR) integrates three cooperative facilities across Johns Hopkins: the Applied Imaging Mass Spectrometry (AIMS) facility, the Mass Spectrometry and Proteomics (MSP) facility, and the Metabolomics unit. The MSMIMO SR offers innovative, integrated multiomic workflows that combine omic technologies for systems biology analysis of cancer cells and tissues using state-of-the-art and novel mass spectrometry-based technologies for molecular tissue imaging (spatialomic), metabolomic and proteomic strategies to accelerate cancer research. AIMS offers rapid matrix-assisted laser desorption/ionization (MALDI) imaging of a variety of biomolecules, including endogenous peptides, proteins, N-glycans, lipids, metabolites, and drugs or drug metabolites in cancer cells, spheroids, organoids or tissue sections at high spatial resolution (5 micron). The MSP Facility offers proteomic labeling and label-free strategies, including multidimensional protein identification technology, parallel reaction monitoring, tandem mass tags and stable isotopic labeled amino acids in cell culture for identification and relative or targeted quantification of novel therapeutic proteins, modifications or pathways, dysregulated in cancers, and for tracking interactions of these targets during changes in signal transduction or formation of protein complexes. The Metabolomics Unit offers high throughput detection and quantification of polar and nonpolar metabolites in tissue or fluid extracts. MSMIMO SR services include experimental design, tissue sectioning, sample preparation, buffer exchange, proteolysis, labeling, derivatizations, chromatography, MALDI imaging, tandem mass spectrometry imaging, image analysis, two-dimensional nanoflow liquid chromatography tandem mass analysis, data analysis and interpretation, and assistance with reporting results, training and data submission to public repositories. Biostatisticians and Bioinformaticians are available for in-depth statistical analyses of spatialomic, metabolomic and proteomic results. The MSMIMO SR provides access and training to proprietary software and equipment for SKCCC investigators who wish to perform their own analysis and offers workshops on operating user- accessible mass spectrometers several times a year. The MSMIMO SR's innovative approaches and workflows provide SKCCC Members with the spatial resolution to compare metabolomes, drug metabolism, lipidomes and proteomes across individual cells or cell clusters within the tumor microenvironment. Our comprehensive, highly multiplexed molecular discovery platforms are designed to advance Center Members' research by revealing molecular networks that drive tumorigenesis. During this funding period, 63 SKCCC investigators have used the MSMIMO SR, and more than 30 manuscripts are attributed to this SR. SKCCC Managed Shared Resource Reporting Period: January 1, 2020 to December 31, 2020