Multi-omics Mass Spectrometry and Biomarker Discovery Core

多组学质谱学与生物标志物发现核心设施共享资源 摘要 多组学质谱学和生物标记物发现核心设施(MMSBD)提供癌症中心 (CC)拥有基于质谱仪(MS)的多组学技术的成员，以支持癌症研究 发病机制、癌症生物标志物、新型抗癌药物和诊断研究。多元组学方法 提供蛋白质组学、多肽组学、糖组学、脂类组学、代谢组学、 和小分子分析。定量磷酸蛋白质组学和深度蛋白质组学是提供的新服务 在本供资期间。核心提供从项目构思到实施的科学咨询 用于准备手稿和拨款申请。 主要核心服务有：1)液-质联用(LC/MS)；2)非靶向/靶向 蛋白质组学，包括无标记定量蛋白质组学以及等压串联稳定同位素标记 培养物中氨基酸的质量标记或稳定同位素标记；3)培养后氨基酸的鉴定和定量 翻译修饰；4)从头开始的多肽/蛋白质序列分析；5)多肽序列验证 GMP条件(核心是FDA注册的)；6)脂质组学和代谢组学；7)从 临床样本；8)小分子、多肽、药物的分析发展和量化，以及验证 潜在生物标志物；9)利用MALDI-MS进行组织生物标志物剖析；以及10)组织成像质谱学。 MMSBD配备了尖端的主要仪器，包括Orbitrap Fusion三元质量 光谱仪(Thermo)；6490三重四极杆质谱仪(Agilent)；几个LC Q-TOF质谱仪 光谱仪(Waters和Agilent)和两台MALDI-MS仪器。第二个高端轨道质量 正在购买光谱仪(Fusion Lumos；Thermo)，以满足对LC/MS仪器日益增长的需求 时间到了。数据分析在核心维护的工作站和多节点计算机集群上执行， 同时运行商业和开放源码软件。软件在不断更新，MS和元数据也在不断更新 自动备份并存储在位于主园区内外的多个冗余存储单元上。 《核心》由马库斯·卡尔库姆博士和罗伯特·希基博士共同执导，他们都是贝克曼公司的教员。 研究所。影响核心的关键决定由咨询委员会审查，咨询委员会由协调委员会组成 使用核心服务的成员。自上一次竞争性更新以来，MMSBD贡献了26 由CC成员出版，并为73名调查人员提供服务，其中52名是CC成员，代表所有五名成员 程序。在52个协调委员会成员中，45个(87%)获得了同行审查的资金。因此，MMSBD提供了 可获得、经济高效且高质量的多组学质谱学和生物标志物发现服务，以 支持希望之城综合癌症中心研究。

Multi-omics Mass Spectrometry & Biomarker Discovery Core Facility Shared Resource ABSTRACT The Multi-omics Mass Spectrometry & Biomarker Discovery Core Facility (MMSBD) provides Cancer Center (CC) members with mass spectrometry (MS)-based multi-omics technology to support research on cancer pathogenesis, cancer biomarkers, novel anti-cancer agents, and diagnostic studies. The multi-omics approaches provided encompass high-quality MS services for proteomics, peptidomics, glycomics, lipidomics, metabolomics, and small molecule analyses. Quantitative phosphoproteomics and deep proteomics are new services provided during the current funding period. The Core offers scientific consultation from project conception and execution to preparation of manuscripts and grant applications. Primary Core services are: 1) liquid chromatographic/mass spectrometry (LC/MS); 2) untargeted/targeted proteomics, including label-free quantitative proteomics as well as stable isotope labeling with isobaric tandem mass tags or stable isotope labeling of amino acids in culture; 3) identification and quantification of post- translational modifications; 4) de novo peptide/protein sequence analysis; 5) peptide sequence validation under GMP conditions (the Core is FDA-registered); 6) lipidomics and metabolomics; 7) biomarker discovery from clinical samples; 8) assay development and quantification of small molecules, peptides, drugs, and validation of potential biomarkers; 9) tissue biomarker profiling by MALDI-MS; and 10) tissue imaging mass spectrometry. The MMSBD is well equipped with cutting-edge major instrumentation including an Orbitrap Fusion Tribrid mass spectrometer (Thermo); a 6490 Triple Quadrupole mass spectrometer (Agilent); several LC Q-TOF mass spectrometers (Waters and Agilent), and two MALDI-MS instruments. A second high-end Orbitrap mass spectrometer (a Fusion Lumos; Thermo) is being purchased to meet increased demands for LC/MS instrument time. Data analyses are performed on Core-maintained workstations and multi-node computer clusters that operate both commercial and open source software. Software is constantly updated and MS and metadata are automatically backed up and stored on several redundant storage units located on and off the main campus. The core is co-directed by Drs. Markus Kalkum and Robert Hickey, who are both faculty within Beckman Research Institute. Key decisions affecting the Core are reviewed by an Advisory Committee, composed of CC members who use the Core’s services. Since the last competitive renewal, the MMSBD contributed to 26 publications by CC members and served 73 investigators, 52 of whom were CC members representing all five Programs. Of the 52 CC members, 45 (87%) had peer-reviewed funding. Accordingly, the MMSBD provides accessible, cost-effective, and high-quality multi-omics mass spectrometry and biomarker discovery services to support the research of the City of Hope Comprehensive Cancer Center.