PNNL Proteome Characterization Center

PNNL 蛋白质组表征中心

• 批准号: 9210313
• 负责人: Tao Liu
• 金额: $ 112.38万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9210313
• 关键词: Achievement; Affinity; Amino Acid Sequence; Area; Bioinformatics; Biological Assay; Cancer Biology; Cancer Diagnostics; Carcinoma; Cell Line; Center for Translational Science Activities; Chromosomal Rearrangement; Classification; Clinical; Collection; Colorectal Cancer; Comb animal structure; Data; Data Analyses; Defect; Development; Disease; Early Diagnosis; Gases; Genome; Genomics; Goals; Hereditary Disease; Human; Informatics; Label; Laboratories; Liquid Chromatography; Malignant Neoplasms; Malignant neoplasm of ovary; Measurement; Metals; Methodology; Methods; Mutation; Ovarian; Pacific Northwest; Pathway Analysis; Patients; Peptides; Performance; Phase; Post-Translational Modification Alteration; Post-Translational Protein Processing; Pre-Clinical Model; Prevention; Process; Proteins; Proteome; Proteomics; Publishing; Research; Resolution; Sample Size; Sampling; Serous; Signal Pathway; Signal Transduction; Specimen; Technology; The Cancer Genome Atlas; Therapeutic; Work; Xenograft procedure; arm; assay development; base; cancer type; data integration; genomic variation; human tissue; improved; informatics infrastructure; instrumentation; malignant breast neoplasm; member; multiple reaction monitoring; new technology; novel; outcome forecast; ovarian neoplasm; pancreatic secretory trypsin inhibitor I; phosphoproteomics; pre-clinical; programs; prospective; proteogenomics; quality assurance; stoichiometry; success; tandem mass spectrometry; technology development; tool; treatment strategy; tumor

PROJECT SUMMARY The overall objective of the PNNL Proteome Characterization Center (PCC) is to integrate genomic information with proteomic technologies to comprehensively characterize the proteome and post-translational modifications (PTMs) as well as the functional interaction of proteins in signaling networks in cancers. As one of the PCCs in the current Clinical Proteomic Tumor Analysis Consortium (CPTAC) program, PNNL successfully applied advanced proteomics capabilities and expertise to the comprehensive proteogenomic and phosphoproteomic characterization of ovarian high-grade serous carcinomas from The Cancer Genome Atlas, and has developed novel mass spectrometric approaches to facilitate the analysis of intact proteins, low stoichiometry PTMs, and extremely small samples. The planned PNNL PCC will build on these achievements and contribute to the success of the CPTAC network by characterizing multiple new tumor types assigned by CPTAC, using both the proven standardized, multiplexed discovery and targeted confirmatory workflows as well as introducing novel technologies and platforms, as appropriate, to improve proteomic measurements. Both human biospecimens and preclinical models provided by NCI will be analyzed. The Discovery Research Arm will comprehensively characterize the proteome and multiple PTM-omes in human biospecimens and preclinical samples of 2-3 cancers with the validated advanced proteomics platforms, integrated workflows and informatics tools, using highly multiplexed isobaric labeling and state-of- the-art liquid chromatography-tandem mass spectrometry instrumentation at a throughput of up to 300 samples per year. The Confirmatory Research Arm will verify the impact of genomic variation on the changes in proteome and PTM-omes with validated targeted proteomics platforms (e.g., multiple reaction monitoring), peptide standards and quality assurance. Up to 100 highly specific, multiplexed targeted proteomics assays for both proteins and PTMs will be developed each year for the confirmatory studies using up to 150 samples per year. We will also refine and validate several developmental strategies and platforms at the PNNL PCC leveraging our on-going technology development in areas such as ultrafast gas phase separations and small- sized sample analysis platforms and methodologies to further improve the throughput and sensitivity in both the discovery and confirmatory studies. The PNNL PCC will work closely with the other PCCs, Proteogenomic Data Analysis Centers and Proteogenomic Translational Research Centers in the CPTAC network on data integration and bioinformatics analysis, as well as translational applications.

项目概要 PNNL 蛋白质组表征中心 (PCC) 的总体目标是整合基因组信息 利用蛋白质组学技术全面表征蛋白质组和翻译后修饰 （PTM）以及癌症信号网络中蛋白质的功能相互作用。作为 PCC 之一 目前临床蛋白质组学肿瘤分析联盟（CPTAC）计划，PNNL成功申请 先进的蛋白质组学能力和专业知识，涵盖全面的蛋白质组学和磷酸化蛋白质组学 癌症基因组图谱中卵巢高级别浆液性癌的特征，并已开发 新颖的质谱方法可促进完整蛋白质、低化学计量 PTM 和 极小的样本。计划中的 PNNL PCC 将在这些成就的基础上再接再厉，并为 CPTAC 网络通过表征 CPTAC 指定的多种新肿瘤类型而取得成功，同时使用 经过验证的标准化、多重发现和有针对性的确认工作流程以及引入 酌情改进蛋白质组测量的新技术和平台。既是人类 将分析 NCI 提供的生物样本和临床前模型。 发现研究部门将全面表征蛋白质组和多个 PTM-omes 人类生物样本和 2-3 种癌症的临床前样本，具有经过验证的高级蛋白质组学 平台、集成工作流程和信息学工具，使用高度多重同量异位标记和状态 最先进的液相色谱-串联质谱仪器，处理量高达 300 个样品 每年。验证性研究部门将验证基因组变异对基因组变化的影响 具有经过验证的目标蛋白质组平台的蛋白质组和 PTM-omes（例如，多重反应监测）， 肽标准和质量保证。多达 100 种高度特异性、多重靶向蛋白质组学检测 每年将开发蛋白质和 PTM 以进行验证性研究，每个样本使用多达 150 个样本 年。我们还将完善和验证 PNNL PCC 的多项发展战略和平台 利用我们在超快气相分离和小型化等领域的持续技术开发 大小的样品分析平台和方法，以进一步提高两种方法的通量和灵敏度 发现和验证性研究。 PNNL PCC 将与其他 PCC、蛋白质组数据分析中心和 CPTAC 网络中关于数据集成和生物信息学的蛋白质基因组转化研究中心 分析以及转化应用。