PNNL Clinical Proteome Characterization Center

PNNL 临床蛋白质组表征中心

基本信息

批准号：
9301181
负责人：
Karin D Rodland
金额：
$ 117.04万
依托单位：
BATTELLE PACIFIC NORTHWEST LABORATORIES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2017-07-31
项目状态：
已结题

项目摘要

The Overall Objective ofthe 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 ofthe 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 ofthe 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-speclfic 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 biomari<er 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. RELEVANCE (See instructions): Despite recent declines in the cancer death rate, cancer remains a significant source of mortality: 25% of all deaths In the US are attributed to cancer. There Is a real clinical need for eariier diagnosis, more accurate prognosis, and more effective therapeutic targeting to improve the outcome for patients with cancer. The PCPCC is dedicated to using the best state-of-the-art and advanced developmental MS platforms and methods, systems biology approaches, and clinical collaborations, to advance the discovery and verification of cancer biomarkers.

PNNL临床蛋白质组表征中心的总体目标（PCPCC）是通过将癌症基因型与癌症表型联系起来来促进癌症生物标志物的发展使用癌症蛋白质组的详细综合和定量表征来补充广泛的癌症基因组图集（TCGA）提供的基因组水平表征。 PCPCC将有助于通过使用鲁棒和定量的计划蛋白质表征中心（PPC）的成功网络的成功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发展平台，用于系统的发现和验证蛋白质生物标志物使用CPTC提供的癌症标本和相关数据，在临床研究中有资格。发现单元将进行测量，从而提供全面和定量的表征提供信息，包括蛋白质丰度，剪接变体，突变和翻译后修饰，以补充CPTC供供培养物的基因组表征。这些样品的基因组信息的广泛数据库将与定量集成 PCPCC进行的蛋白质组学测量，其他可用的蛋白质组学信息（例如，来自其他PCC），以及对肿瘤特定途径的系统级分析，以生成高度凭证的优先级列表基于多种信息来源的加权整合，包括临床肿瘤学和癌症生物学。验证单元将系统地开发和应用针对特定蛋白质的多路复用验证测定法由生物标志物候选者选择小组委员会确定和选择的目标。 PCPCC将开发敏感，选择性，定量测定最少每年100个蛋白质靶标，并应用超敏感性每年至少有500个血浆（或血清）样品的吞吐量，对生物组织进行测定，总计至少2500个样品。此外，与发现工作一样，具有最佳可用验证的测量值平台将通过使用开发高性能平台进行的测量来增强平台样本（每年至少总计至少1000个样本，总计> 5000个样本），以提供定量低丰度的测量，原本无法检测到的候选人。作为PCC财团的一部分，PCPCC还将努力根据例如这产生的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努力。相关性（请参阅说明）：尽管最近癌症死亡率下降，但癌症仍然是重要的死亡率来源：美国所有死亡人数中有25％归因于癌症。对Eariier有真正的临床需求诊断，更准确的预后和更有效的治疗靶向，以改善患者的预后癌症。 PCPCC致力于使用最好的最新和先进的发展性MS 平台和方法，系统生物学方法和临床合作，以提高发现和验证癌症生物标志物。