Cancer Proteome Center at Washington Univ, Univ of North Carolina & Boise State

华盛顿大学、北卡罗来纳大学癌症蛋白质组中心

• 批准号: 8323218
• 负责人: XIAN CHEN
• 金额: $ 218.56万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-22 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8323218
• 关键词: Address; Affinity; Antibodies; Automobile Driving; Award; Bioinformatics; Biological; Biological Assay; Biological Markers; Biometry; Blood; Blood specimen; Cancer Biology; Cancer Diagnostics; Clinical; Clinical Data; Collection; Complex; Critical Pathways; Data; Development; Development Plans; Diagnosis; Diagnostic; Disease; Early Diagnosis; Early treatment; Epigenetic Process; Epitopes; Frequencies; Gene Dosage; Genes; Genome; Genomics; Goals; Growth; Human; Immunoassay; Incidence; Individual; Institution; Instruction; Knowledge; Label; Lead; Life; Malignant Neoplasms; Maps; Mass Spectrum Analysis; Measures; Metabolism; Methods; Minor; Mus; Mutation; Normal Range; North Carolina; Organ; Pathway interactions; Patients; Pattern; Peptide antibodies; Peptides; Phase; Plasma; Point Mutation; Post-Translational Protein Processing; Property; Protein Databases; Proteins; Proteome; Proteomics; Publishing; RNA Splicing; Recurrence; Research; Research Infrastructure; Resolution; Resources; Route; Sampling; Sampling Studies; Sensitivity and Specificity; Shotguns; Somatic Cell; Somatic Mutation; Statistical Models; System; Technology; TimeLine; Tissues; Translating; Translations; Validation; Variant; Washington; Xenograft Model; Xenograft procedure; advanced disease; base; cancer genome; cancer genomics; clinical application; clinical practice; data management; experience; genome sequencing; instrumentation; interest; loss of function mutation; malignant breast neoplasm; meetings; mortality; multiple reaction monitoring; mutant; operation; peripheral blood; programs; protein aminoacid sequence; tool; tumor

DESCRIPTION 4 OVERVIEW OF THE PROPOSED PROTEOMIC CHARACTERIZATION CENTERS 4 1. DISCOVERY UNIT - BIOMARKER DISCOVERY 11 2. VERIFICATION UNIT - BIOMARKER VERIFICATION 16 A. ADMINISTRATIVE CORE - INTERNAL MANAGEMENT COMMITTEE (IMC) 21 B. TECHNOLOGY/PLATFORM DEVELOPMENT PLAN 22 C. BIOINFORMATICS/BIOSTATISTICS 25 D. HUMAN SAMPLES/STUDIES 28 SPECIAL EMPHASIS PANEL ROSTER DESCRIPTION (provided by applicant): DESCRIPTION (provided by applicant): Biomarkers are unique, detectable signatures of cancer that are vital to early diagnosis and treatment. The causes of many cancers are somatic mutations in critical pathways that serve organ growth and metabolism. For over a decade there have been intense proteomic efforts to find biomarkers with clinical utility. There are thousands of published studies and thousands of candidate biomarkers of unknown value for the management of cancer. With the advent of whole genome sequencing, the challenge and immense potential value of characterizing the cancer proteome the readout of the genome-is unfolding. A new paradigm is therefore emerging -"genome-out" directed proteomics. In this application, we propose a comprehensive, blood-based, protein biomarker discovery and verification pipeline that addresses biomarker discovery by starting where the cancer biology begins: with the driving somatic mutations. In the discovery phase, we will use information about recurrent genomic mutations in cancer (i.e. those that occur with a greater than 5% incidence in any given cancer) that are identified by ongoing whole-genome sequencing efforts to focus our collection and analyses of high-throughput, quantitative proteomic data on samples provided by the NCI CPTC in concert with unique resources such as comprehensively sequenced "human in mouse" breast cancer xenografts. Proteomic analyses will include a multiplicity of high-resolution, current and advanced proteomics methods that can characterize intact proteins, massively complex peptide mixtures and protein modifications to elucidate the proteomic facade of cellular pathways and networks. Bioinformatic tools with rigorous statistical models will be applied to meet the challenges of querying the genome directly with proteomic data (proteogenomics). This will provide the orthogonality that cancer genomics requires to biologically validate copy number alterations, point mutations, splice variants, and the complex biological effects from loss of function mutations and epigenetic changes and translate these findings into actionable clinical information. With this melding of proteomic and genomic knowledge, clinically and biologically informed decisions will be made to select candidate biomarkers. The properties of each candidate will be verified by demonstrating an ability of the biomarker assay to reliably distinguish between blood samples taken from healthy individuals from those accrued from patients with cancer. RELEVANCE (See instructions): While early diagnosis can lead to treatments to eliminate a malignancy before the lethal phase, there are presently few clinically viable diagnostics that can be used as a reliable marker for the need for early intervention. Therefore, the goal of this project is to assist the CPTC in discovering new biomarkers, verifying their clinical applicability, and ultimately, helping translate selected biomarkers into clinical practice to reduce mortality from cancer.

描述4 拟议蛋白质组学表征中心的概述4 1。发现单位 - 生物标志物发现11 2。验证单元 - 生物标志物验证16 A.行政核心 - 内部管理委员会（IMC）21 B.技术/平台开发计划22 C.生物信息学/生物统计学25 D.人类样本/研究28 特别重点面板名册 描述（由申请人提供）：描述（申请人提供）：生物标志物是独特的，可检测到的癌症特征，对于早期诊断和治疗至关重要。许多癌症的原因是在临界途径中的体细胞突变，可服务器官生长和代谢。十多年来，一直存在巨大的蛋白质组学努力来找到具有临床实用性的生物标志物。有成千上万的已发表研究和成千上万的癌症管理价值的候选生物标志物。随着整个基因组测序的出现，表征癌症蛋白质组的挑战和巨大潜在价值，基因组IS的读数展开。因此，新的范式正在出现 - “基因组”定向蛋白质组学。在此应用中，我们提出了一个综合，基于血液的，蛋白质生物标志物的发现和验证管道，该管道通过开始癌症生物学开始的地方来解决生物标志物发现：驱动体细胞突变。 In the discovery phase, we will use information about recurrent genomic mutations in cancer (i.e. those that occur with a greater than 5% incidence in any given cancer) that are identified by ongoing whole-genome sequencing efforts to focus our collection and analyses of high-throughput, quantitative proteomic data on samples provided by the NCI CPTC in concert with unique resources such as comprehensively sequenced "human in mouse" breast cancer xenografts.蛋白质组学分析将包括多种高分辨率，当前和先进的蛋白质组学方法，这些方法可以表征完整的蛋白质，大规模复杂的肽混合物和蛋白质修饰，以阐明细胞途径和网络的蛋白质组学外观。具有严格统计模型的生物信息学工具将用于应对直接使用蛋白质组学数据（蛋白质组学）直接查询基因组的挑战。这将提供正交性，即癌症基因组学需要在生物学上验证拷贝数改变，点突变，剪接变异以及功能突变丧失和表观遗传学变化所带来的复杂生物学作用，并将这些发现转化为可行的临床信息。通过这种蛋白质组学和基因组知识的融合，将在临床和生物学上的知情决定中做出选择候选生物标志物。将通过证明生物标志物测定能力可靠地区分健康个体的血样与从癌症患者中的患者可靠地区分血液样本的能力来验证每个候选者的特性。 相关性（请参阅说明）：虽然早期诊断可以导致治疗以消除致命阶段之前的恶性肿瘤，但目前很少有临床可行的诊断能够用作早期干预需要的可靠标记。因此，该项目的目的是帮助CPTC发现新的生物标志物，验证其临床适用性，并最终帮助将选定的生物标志物转化为临床实践，以降低癌症的死亡率。