Center for Application of Advanced Clinical Proteomic Technologies for Cancer

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表征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) 提供的广泛基因组水平表征，从而促进癌症生物标志物的开发。 PCPCC 将利用强大的定量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 提供的癌症样本和相关数据，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，为计划中的蛋白质表征中心 (PPC) 网络的成功做出贡献。发现单元将进行测量，提供癌症蛋白质组的全面和定量表征，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 提供的生物样本的基因组表征。这些样本的基因组信息的广泛数据库将与 PCPCC 进行的定量蛋白质组学测量、其他可用的蛋白质组学信息（例如，来自其他 PCC 的）以及肿瘤特异性途径的系统级分析相整合，以基于多种信息来源（包括临床肿瘤学和癌症生物学）的加权整合，生成高度可信的候选者的优先列表。验证部门将系统地开发和应用针对生物标志物候选选择小组委员会确定和选择的特定蛋白质靶标的多重验证测定。 PCPCC 每年将开发针对至少 100 个蛋白质靶标的灵敏、选择性、定量测定，并将超灵敏测定应用于生物识别验证，每年至少处理 500 个血浆（或血清）样本，总共至少 2500 个样本。此外，与 Discovery 工作一样，使用最佳可用验证平台进行的测量将通过使用开发高性能平台对相同样品进行测量来增强（每年总共至少 1000 个样品，总计 > 5000 个样品），从而为低丰度、否则无法检测到的候选物提供定量测量。作为 PCC 联盟的一部分，PCPCC 还将致力于推进其他人的努力，例如：生成的癌症肿瘤蛋白质组学数据，以及随后的生物标志物临床鉴定和验证工作。

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.