Proteome Characterization Center: A Genoproteomics Pipeline for Cance Research

在这一应用中，我们建议建立一个整合的蛋白质组表征中心(PCC)，其中包括 杰出的科学家和临床医生团队，以构建使用 基因蛋白质组学方法。这个多学科团队由国际公认的专家组成， 临床肿瘤学、临床化学、癌症生物学、蛋白质组学技术、蛋白质组学/基因组学 生物信息学、生物统计学和实验设计、计量/标准、技术优化、化验 建设、项目管理和患者倡导。该计划是将基因组学与蛋白质组学联系起来 (基因蛋白质组学)。我们相信基因组数据提供了一条非常有价值的分子途径 识别可用于检测、鉴别诊断、预后的基因和途径 癌症的预测和治疗靶点。蛋白质组学方法将提供对 蛋白质固有的独特功能，包括翻译后修饰，如糖基化 和磷酸化。我们提出了一个两步策略来构建基于证据的蛋白质组生物标记物。 卵巢癌和其他癌症的治疗管道。第一步是发现候选生物标记物 利用质谱学和亲和力技术获得包括TCGA在内的人类基因组数据 标本。其目标是综合表征肿瘤和正常的生物标本，并鉴定其 蛋白质组成，以便系统地识别和优先考虑癌症相关蛋白质的进展 去核实一下。第二步是使用有针对性的化验对这些候选人进行核实。我们的目标是 使用优化和标准化的方法生成准确、可重复性、灵敏、定量的多重分析 已发现的生物标志物的高通量技术。虽然这项提议并不打算进行 大规模的临床研究，我们相信最终的临床应用和表现 应明确规定这些检测方法的特点。有了这个多学科的杰出团队 科学家和临床医生，我们的PCC为生物标志物的发现和成功提供了最好的机会 个性化癌症药物的验证。 相关性(请参阅说明)： 了解分子网络在癌症发生中的作用是成功开发 降低癌症死亡率的战略。基于从TCGA和其他组织中发现的基因组改变 消息人士称，这项提案将侧重于开发一种临床有用的蛋白质生物标记物管道，使用 用于个性化癌症药物的最先进的蛋白质组学技术。

In this application, we propose to establish an integrated proteome characterization center (PCC) with an outstanding team of scientists and clinicians in order to construct a cancer biomarker pipeline using genoproteomic approaches. This multidisciplinary team consists of internationally recognized experts in clinical oncology, clinical chemistry, cancer biology, proteomic technologies, proteomics/genomics-specific bioinformatics, biostatistics and experimental design, metrology/standards, technology optimization, assay construction, project management and patient advocacy. The plan is to connect genomics with proteomics (genoproteomics). We believe that genomic data provides a highly valuable molecular route towards the identification of genes and pathways that could be useful forthe detection, differential diagnosis, outcome prediction and therapeutic targets of cancer. The proteomic approaches will provide the identification of unique features that are inherent to proteins including post-translational modifications, such as glycosylation and phosphorylation. We propose a two- step strategy to construct an evidence-based, proteomic biomarker pipeline for ovarian and other carcinomas. The first step is the discovery of candidate biomarkers from genomic data including TCGA using mass spectrometry and affinity based technologies on human specimens. The goal is to comprehensively characterize tumor and normal biospecimens and identify their protein composition in order to systematically identify and prioritize cancer-related proteins for advancement to verification. The second step is the verification of these candidates using targeted assays. The goal is to generate accurate, reproducible, sensitive, quantitative, multiplex assays using optimized and standardized high-throughput technologies forthe discovered biomarkers. While this proposal is not intended to conduct large scale clinical studies, we believe that the ultimate clinical application and the performance characteristics of these assays should be clearly defined. With this multidisciplinary team of outstanding scientists and clinicians, our PCC offers the best opportunity forthe success of biomarker discovery and verification for personalized cancer medicine. RELEVANCE (See instructions): Understanding the molecular networking in carcinogenesis is essential forthe development of a successful strategy to reduce cancer mortality. Based on the genomic alterations identified from TCGA and other sources, this proposal will focus on the development of a clinically useful protein biomarker pipeline using state-of-the art proteomics technologies for personalized cancer medicine.