Center for Application of Advanced Clinical Proteomic Technologies for Cancer

先进癌症临床蛋白质组学技术应用中心

• 批准号: 8521192
• 负责人: Karin D Rodland
• 金额: $ 274.86万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-26 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8521192
• 关键词: Biological Assay; Biological Markers; Biometry; Blood capillaries; Cancer Biology; Cancer Death Rates; Cessation of life; Clinical; Clinical Oncology; Clinical Research; Collaborations; Complement; Data; Data Analyses; Databases; Development; Dimensions; Early Diagnosis; Genome; Genomics; Genotype; Hybrids; Individual; Instruction; Ions; Link; Malignant Neoplasms; Mass Spectrum Analysis; Measurement; Methods; Metric; Mutation; Outcome; Output; Pathway interactions; Patients; Peptides; Performance; Phenotype; Plasma; Post-Translational Protein Processing; Process; Proteins; Proteome; Proteomics; Qualifying; Quality Control; RNA Splicing; Resolution; Sampling; Selection Criteria; Serum; Source; Specimen; Staging; System; Systems Biology; Technology; The Cancer Genome Atlas; Validation; Variant; Weight; Work; assay development; base; cancer genome; candidate selection; capillary; improved; ion mobility; mortality; multiple reaction monitoring; oncology; outcome forecast; quality assurance; success; therapeutic target; tumor

DESCRIPTION (provided by applicant): The Overall Objective of the PNNL Clinical Proteome Characterization Center (PCPCC) is to facilitate cancer biomarker development by linking the cancer genotype to the cancer phenotype using detailed comprehensive and quantitative characterization of cancer proteomes to complement the extensive genome-level characterization provided by The Cancer Genome Atlas (TCGA). The PCPCC will contribute to the success of the planned network of Protein Characterization Centers (PPCs) by utilizing robust and quantitative proteomics technologies and workflows, including simultaneous application of state-of-the-art validated platforms and advanced developmental platforms, for systematic discovery and verification of protein biomarkers that can be qualified in clinical studies, using the cancer specimens and associated data provided by the CPTC. The Discovery Unit will make measurements providing a comprehensive and quantitative characterization of the cancer proteomes that provides Information including protein abundances, splicing variants, mutations, and posttranslational modifications to complement the genomic characterization for CPTC-supplied biospecimens. The extensive database of genomic information on these samples will be integrated with the quantitative proteomic measurements made by the PCPCC, other available proteomics Information (e.g., from other PCC's), and a systems-level analysis of tumor-specific pathways to produce a prioritized list of highly credentialed candidates based on a weighted integration of multiple sources of Information, including clinical oncology and cancer biology. The Verification Unit will systemically develop and apply multiplexed verification assays directed at specific protein targets as identified and selected by the Biomarker Candidate Selection Subcommittee. The PCPCC will develop sensitive, selective, quantitative assays for a minimum of 100 protein targets per year and apply ultra-sensitive assays to biometric verification with a throughput of at least 500 plasma (or serum) samples per year, for a total of at least 2500 samples. Additionally, as in the Discovery efforts, measurements with the best available validated platform will be augmented by measurements with a developmental high performance platform for the same samples (for an overall total of at least 1000 samples per year, and >5000 total) to provide quantitative measurements for low-abundance otherwise undetectable candidates. As part of a consortium of PCC's, the PCPCC will also work to advance the efforts of others based upon e.g. the cancer tumor proteomics data generated, as well as subsequent biomarker clinical qualification and validation efforts.

描述(由申请人提供)：PNNL临床蛋白质组表征中心(PCPCC)的总体目标是通过使用癌症蛋白质组的详细、全面和定量的表征来将癌症基因型与癌症表型联系起来，以补充癌症基因组图谱(TCGA)提供的广泛的基因组水平表征，从而促进癌症生物标记物的开发。PCPCC将利用稳健和定量的蛋白质组学技术和工作流程，包括同时应用最先进的验证平台和先进的开发平台，利用CPTC提供的癌症标本和相关数据，系统地发现和验证可在临床研究中合格的蛋白质生物标志物，从而为计划中的蛋白质表征中心网络的成功做出贡献。发现股将进行测量，提供癌症蛋白质组的全面和定量特征，提供包括蛋白质丰度、剪接变体、突变和翻译后修饰在内的信息，以补充CPTC提供的生物标本的基因组特征。关于这些样本的基因组信息的广泛数据库将与PCPCC进行的定量蛋白质组测量、其他可用蛋白质组学信息(例如，来自其他PCC的)以及对肿瘤特定途径的系统级分析相结合，以基于包括临床肿瘤学和癌症生物学在内的多种信息源的加权整合来产生高资质候选的优先列表。核查股将针对生物标记物候选选择小组委员会确定和选定的特定蛋白质目标，系统地开发和应用多重核查分析。PCPCC将开发每年至少100个蛋白质目标的敏感、选择性和定量分析，并将超敏感分析应用于生物测定验证，每年至少处理500个血浆(或血清)样本，总计至少2500个样本。此外，与Discovery的努力一样，利用最佳可用的验证平台进行的测量将通过开发高性能平台对相同的样品进行测量(总计每年至少1000个样品，总共5000个样品)，以提供对低丰度否则无法检测的候选样品的定量测量。作为PCC联盟的一部分，PCPCC还将根据产生的癌症肿瘤蛋白质组学数据以及随后的生物标记物临床鉴定和验证工作，努力推动其他组织的努力。