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.

项目摘要 PNNL蛋白质组表征中心（PCC）的总体目标是整合基因组信息 借助蛋白质组学技术，可以全面地表征蛋白质组和翻译后修饰 （PTMS）以及癌症中蛋白质在癌症中的功能相互作用。作为PCC之一 当前的临床蛋白质组学分析联盟（CPTAC）计划，PNNL成功应用了 综合蛋白质组学和磷蛋白质组学的先进蛋白质组学能力和专业知识 从癌症基因组地图集的卵巢高级浆液性癌的表征，并发展了 新型的质谱方法，以促进完整蛋白质，低化学计量PTM和 非常小的样品。计划中的PNNL PCC将基于这些成就，并为 CPTAC网络通过表征CPTAC分配的多种新肿瘤类型的成功，使用两者 经过验证的标准化，多重发现和有针对性的确认工作流以及引入 适当的新技术和平台，以改善蛋白质组学测量。两个人 NCI提供的生物测量和临床前模型将进行分析。 发现研究部门将全面地表征蛋白质组和多个ptm-omes 具有经过验证的高级蛋白质组学的2-3个癌症的人类生物测量和临床前样品 平台，集成的工作流和信息学工具，使用高度多重的同质标签和最新 ART液相色谱串联质谱仪器，最多300个样品的吞吐量 每年。验证性研究部门将验证基因组变异对变化的影响 具有经过验证的靶向蛋白质组学平台（例如，多个反应监测）的蛋白质组和PTM-OMES， 肽标准和质量保证。多达100个高度特定的多重靶向蛋白质组学测定 每年都会开发蛋白质和PTM，用于使用多达150个样品的验证性研究 年。我们还将在PNNL PCC中完善并验证几种发展策略和平台 利用我们正在进行的技术开发在超快气相分离和小型领域 大小的样本分析平台和方法，以进一步提高两者的吞吐量和灵敏度 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网络中的蛋白质组转化研究中心数据集成和生物信息学 分析以及翻译应用。