A Proteomic Platform to identify and Validate Biomarkers in Metabolic Syndrome and Coronary Artery Disease

用于识别和验证代谢综合征和冠状动脉疾病生物标志物的蛋白质组学平台

• 批准号: 8887497
• 负责人: W. Andy Tao
• 金额: $ 29.71万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8887497
• 关键词: Adopted; Animal Model; Atherogenic Diet; Automation; Biochemical; Biological Assay; Biological Markers; Biological Models; Chemicals; Clinical; Coronary Arteriosclerosis; Detection; Development; Diagnosis; Disease; Early Diagnosis; Employee Strikes; Family suidae; Fractionation; Genotype; Goals; Immune; Ions; Life; Link; Measurable; Measures; Metabolic syndrome; Metals; Methods; Modeling; Molecular; Obesity; Patient Monitoring; Patients; Physiological; Plasma; Plasma Proteins; Polymers; Procedures; Proteins; Proteome; Proteomics; Protocols documentation; Reproducibility; Sampling; Solutions; Source; Staging; Testing; Therapeutic; Time; Tissues; United States National Institutes of Health; Validation; base; candidate marker; clinical application; cost; data acquisition; design; disease diagnosis; feeding; high risk; improved; meetings; nanopolymer; novel; outcome forecast; screening; tool; verification and validation

Blood plasma/serum has remained a major sample source for the detection of disease biomarker candidates with its easy accessibility and measurable tissue-derived proteins that hold potential to uncover physiological and pathological changes during diseases. Proteomics-based biomarker discovery using plasma/serum, however, is severely limited by the high complexity and dynamic range of protein concentrations (10-12 orders of magnitude). Presently, a majority of plasma/serum proteomic strategies are lack of adequate reproducibility, sensitivity, and robustness for clinical tests. Solutions for these serious technological barriers to develop a reliable detection platform toward clinical implementation are elusive. The long term goal of this project is to establish a robust proteomic platform that is translational, sensitive, and reproducible for biomarker discovery, verification and validation, with an emphasis on the identification and validation of plasma biomarkers for metabolic syndrome and early detection of coronary artery disease (CAD). We propose to develop a distinctive platform based on metal ion functionalized soluble nanopolymers for efficient and selective isolation of subsets of low abundant plasma proteins. We will test this approach by focusing on Ossabaw swine as our model system and will establish protocols that will ultimately provide a powerful method for any biofluid-based biomarker discovery. We propose to profile plasma proteomes as a function of feeding time and to correlate with physiological and pathological parameters over the period in which the Ossabaw swine develop metabolic syndrome. There is an increasingly urgent and strong push of proteomic discoveries to clinical applications. This project is based on a distinctive new concept and once developed, it will dramatically simplify the procedure and enhance our ability to sensitively identify candidate markers. As a consequence, the results of this study will have an important positive impact, not only on the development of novel tools for proteomics-based biomarker discovery, but also toward improving disease therapeutics and facilitating more effective diagnosis.

血浆/血清仍然是检测疾病生物标志物的主要样本来源 候选者具有易于获取和可测量的组织衍生蛋白，有潜力 揭示疾病期间的生理和病理变化。基于蛋白质组学的生物标志物 然而，使用血浆/血清的发现受到高复杂性和动态范围的严重限制 蛋白质浓度（10-12 个数量级）。目前，大多数血浆/血清蛋白质组学 策略缺乏足够的临床试验重现性、灵敏度和稳健性。解决方案 这些严重的技术障碍阻碍了开发可靠的临床检测平台 实施难以捉摸。该项目的长期目标是建立一个强大的蛋白质组平台 对于生物标志物的发现、验证和确认来说，这是可转化的、敏感的和可重复的， 强调代谢综合征血浆生物标志物的鉴定和验证 早期发现冠状动脉疾病（CAD）。我们建议开发一个有特色的平台 金属离子功能化可溶性纳米聚合物，用于高效、选择性地分离低分子量子集 丰富的血浆蛋白。我们将重点关注奥萨巴猪作为我们的模型来测试这种方法 系统并将建立协议，最终为任何基于生物流体的 生物标志物的发现。我们建议将血浆蛋白质组作为喂养时间的函数进行分析，并 与奥萨巴猪生长期间的生理和病理参数相关 出现代谢综合征。蛋白质组学发现的推动力日益迫切和强劲 到临床应用。该项目基于独特的新概念，一旦开发，它将 大大简化了程序并增强了我们灵敏地识别候选标记的能力。 因此，这项研究的结果将产生重要的积极影响，不仅对 开发基于蛋白质组学的生物标志物发现的新工具，同时也致力于改进 疾病治疗并促进更有效的诊断。