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源 具有易于访问性和可测量组织衍生的蛋白质的候选者 发现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 但是，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 策略缺乏足够的可重复性，灵敏度和鲁棒性来进行临床测试。解决方案 这些严重的技术障碍，以开发可靠的检测平台来临床 实施是难以捉摸的。该项目的长期目标是建立一个强大的蛋白质组学平台 对于生物标志物发现，验证和验证，这是转化，敏感和可重复的 强调对代谢综合征的血浆生物标志物的识别和验证 早期检测冠状动脉疾病（CAD）。我们建议开发基于独特平台的 在金属离子官能化可溶性纳米聚合物上，以有效和选择性隔离低的子集 丰富的血浆蛋白。我们将通过专注于Ossabaw Swine作为我们的模型来测试这种方法 系统并将建立最终为任何基于生物流体的方法提供强大方法的协议 生物标志物发现。我们建议将血浆蛋白质组概述为喂养时间的函数和 在Ossabaw Swine的时期内，与生理和病理参数相关 发展代谢综合征。蛋白质组学发现越来越紧迫和强烈地推动 用于临床应用。该项目基于一个独特的新概念，一旦发展，它将 极大地简化了过程，并增强了我们敏感识别候选标记的能力。 结果，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新型工具，但也要改善 疾病疗法并促进更有效的诊断。