Vanderbilt Proteome Characterization Center

范德比尔特蛋白质组表征中心

• 批准号: 8325002
• 负责人: Daniel C Liebler
• 金额: $ 283.21万
• 依托单位: VANDERBILT UNIVERSITY
• 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/8325002
• 关键词: Antibodies; Area; Biological Assay; Biological Markers; Blood Tests; Cancer Biology; Cancer Center; Cancer Diagnostics; Characteristics; Chromatography; Clinical; Collaborations; Collection; Colon Carcinoma; Colonoscopy; Computer software; Data; Data Set; Detection; Development; Diagnosis; Diagnostic tests; Disease; Early Diagnosis; Evaluation; Evolution; Funding; Generations; Genes; Genomics; Goals; Human; Informatics; Institutes; Knowledge; Label; Leadership; Link; Liquid Chromatography; Malignant Neoplasms; Mass Spectrum Analysis; Methods; Modeling; Molecular Abnormality; National Cancer Institute; Patients; Peptides; Performance; Phase; Phenotype; Phosphoproteins; Plasma; Play; Process; Proteins; Proteome; Proteomics; Quality Control; Reagent; Research Infrastructure; Resources; Role; Signal Pathway; Signal Transduction; Specific qualifier value; Specimen; System; Technology; Technology Assessment; The Cancer Genome Atlas; Tissue Banks; Tissues; Translating; Tumor Tissue; Variant; Work; base; cancer genome; cancer therapy; clinically relevant; cohort; human tissue; innovation; multiple reaction monitoring; novel diagnostics; programs; protein expression; protein function; sample collection; success; tandem mass spectrometry; tool; tumor

DESCRIPTION (provided by applicant): The Cancer Genome Atlas (TCGA) initiative, by generating comprehensive genomic characterization of diverse human cancers, poses the critical question of how genomic variation translates to cancer. Genomic abnormalities are thought to drive cancer phenotypes through their effects on proteins and proteomes, which can be analyzed by systematic application of new proteomic technologies. The National Cancer Institute (NCI) Clinical Proteomic Technology Assessment for Cancer (CPTAC) initiative has implemented standardized technology platforms in a biomarker development pipeline and, as one of the initial 5 CPTAC programs, we have made a major contribution to this effort. We have already pioneered this pipeline for cancer biomarker development through the Jim Ayers Institute for Precancer Detection and Diagnosis, a unique initiative established in the Vanderbilt-lngram Cancer Center. This application proposes the Vanderbilt Proteome Characterization Center (Vanderbilt PCC) built on the expertise and infrastructure of the Ayers Institute. The overall goal of the Vanderbilt PCC is to integrate genomic information with proteomic technologies to discover and verify protein biomarkers for cancer. To analyze genomically characterized tumor tissue biospecimens from the TCGA program, we will apply standardized liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM-MS) platforms. These analyses will encompass global protein expression changes and changes in phosphorylated and acetylated proteins that regulate signaling networks in cancer. The Vanderbilt PCC will integrate TCGA-derived genomic data and other relevant information into the discovery process and develop systematic approaches to prioritize biomarker candidates. We will verify biomarker candidates in clinically relevant cohorts with standardized, targeted analyses. We will also advance technologies for assessment of signaling networks and functional subproteomes, the integration of genomic and proteomic data and the evaluation of analytical system performance. The Vanderbilt PCC brings to the CPTC network a fully integrated program with expertise in all of the critical areas specified by the RFA.

描述（由申请人提供）：癌症基因组图谱（TCGA）计划通过生成各种人类癌症的综合基因组表征，提出了基因组变异如何转化为癌症的关键问题。基因组异常被认为通过其对蛋白质和蛋白质组的影响来驱动癌症表型，这可以通过系统地应用新的蛋白质组学技术来分析。美国国家癌症研究所（NCI）癌症临床蛋白质组学技术评估（CPTAC）计划在生物标志物开发管道中实施了标准化技术平台，作为最初的5个CPTAC计划之一，我们为这一努力做出了重大贡献。我们已经通过Jim Ayers癌症前检测和诊断研究所开创了这一癌症生物标志物开发管道，这是范德比尔特-英格拉姆癌症中心建立的一项独特举措。本申请提出了建立在艾尔斯研究所的专业知识和基础设施上的范德比尔特蛋白质组表征中心（范德比尔特PCC）。范德比尔特PCC的总体目标是将基因组信息与蛋白质组学技术相结合，以发现和验证癌症的蛋白质生物标志物。为了分析TCGA项目中具有基因组特征的肿瘤组织生物标本，我们将应用标准化液相色谱-串联质谱（LC-MS/MS）和液相色谱-多反应监测质谱（LC-MRM-MS）平台。这些分析将包括全球蛋白质表达变化以及调节癌症信号网络的磷酸化和乙酰化蛋白质的变化。范德比尔特PCC将把TCGA衍生的基因组数据和其他相关信息整合到发现过程中，并开发系统的方法来优先考虑生物标志物候选物。我们将通过标准化、有针对性的分析来验证临床相关队列中的生物标志物候选者。我们还将推进信号网络和功能亚蛋白质组的评估，基因组和蛋白质组数据的整合以及分析系统性能评估的技术。范德比尔特PCC为CPTC网络带来了一个完全集成的计划，在RFA指定的所有关键领域都具有专业知识。