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: 8153493
• 负责人: Karin D Rodland
• 金额: $ 304.55万
• 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 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8153493
• 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）的总体目标是通过将癌症基因型与癌症蛋白质组的详细综合和定量表征联系起来，以促进癌症生物标志物的发育，以补充癌症基因组基因组的扩展特征。 PCPCC将通过利用强大和定量的蛋白质组学技术和工作流程，包括同时在临床研究中使用蛋白质生物标记的蛋白质生物标志，并使用癌症的蛋白质生物标记，将有助于使用癌症的蛋白质生物标志，并使用临床研究criptical criptical carteric criptical carterc，PCPCC将通过使用可靠的和先进的开发平台的同时应用，在临床研究中使用蛋白质生物标志，并使用癌症的数据criptical criptical criptical carteric criptical criptical carteric carts carts carts，PCPCC将有助于计划的蛋白质表征中心（PPC）的成功。该发现单元将进行测量，从而为癌症蛋白质组提供全面和定量的表征，这些蛋白质组提供了包括蛋白质丰度，剪接变体，突变和翻译后修饰的信息，以补充CPTC添加的生物素的基因组表征。 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.验证单元将系统地开发并应用针对特定蛋白质靶标的多路复用验证测定法，并由生物标志物候选者选择子委员会选择和选择。 PCPCC每年至少有100个蛋白质靶标的敏感，选择性的定量测定，并以每年至少500个血浆（或血清）样品的吞吐量对生物识别验证进行超敏感测定，总计至少2500个样品。此外，与发现工作一样，具有最佳可用验证平台的测量值将通过具有开发高性能平台的相同样本的高性能平台（总计每年至少1000个样本，总计> 5000个）的测量值来提供，以提供对低资源不足的否则无法检测到的候选人的定量测量。作为PCC财团的一部分，PCPCC还将努力根据例如产生了癌症肿瘤蛋白质组学数据，以及随后的生物标志物临床资格和验证工作。