PNNL Clinical Proteome Characterization Center

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开发 使用癌症蛋白质组的详细、全面和定量表征， 癌症基因组图谱（TCGA）提供的基因组水平表征。PCPCC将为 成功的计划网络的蛋白质表征中心（PPC），通过利用强大的和定量的 蛋白质组学技术和工作流程，包括同时应用最先进的经验证的平台 和先进的开发平台，用于系统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进行临床研究。 发现单位将进行测量，提供全面和定量的特点， 癌症蛋白质组，提供包括蛋白质丰度、剪接变体、突变和 翻译后修饰，以补充CPTC提供的生物标本的基因组表征。 这些样本的基因组信息的广泛数据库将与定量分析相结合。 由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）， 以及对肿瘤特异性途径的系统级分析，以产生高度可信的 基于多个信息来源的加权整合的候选人，包括临床肿瘤学和 癌症生物学 核查股将有系统地开发和应用针对特定蛋白质的多重核查化验 由生物标志物候选选择小组委员会鉴定和选择的靶标。PCPCC将发展 每年至少检测100个蛋白质靶点的灵敏、选择性、定量检测， 从分析到生物安全验证，每年至少有500份血浆（或血清）样本，总计 至少2500个样本。此外，在探索工作中，最佳可用的测量验证了 该平台将通过测量得到增强，同时还将开发一个高性能平台， 样本（每年总计至少1000个样本，且总计>5000个），以提供定量 测量低丰度，否则无法检测的候选人。 作为PCC联盟的一部分，PCPCC还将努力推动其他人的努力，例如， 生成的癌症肿瘤蛋白质组学数据，以及后续的生物标志物临床鉴定和验证 努力 相关性（见说明）：尽管最近癌症死亡率下降，癌症仍然是一个显着的 死亡原因：在美国，25%的死亡归因于癌症。临床上有真实的需要 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 得了癌症PCPCC致力于使用最先进和先进的开发MS 平台和方法，系统生物学方法和临床合作，以推进发现和 癌症生物标志物的验证。

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.