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

血浆/血清仍然是检测疾病生物标志物的主要样本来源。 候选蛋白具有易获得性和可测量的组织衍生蛋白，具有潜在的 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记物 然而，使用血浆/血清的发现受到高度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 临床试验缺乏足够的重复性、敏感性和稳健性。解决方案 这些严重的技术障碍阻碍了向临床开发可靠的检测平台 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平台 这对于生物标记物的发现、验证和验证是可翻译的、敏感的和可重现的， 重视代谢综合征和糖尿病患者血浆生物标志物的识别和验证 早期发现冠状动脉疾病(CAD)。我们建议开发一个独特的平台，基于 金属离子功能化可溶纳米聚合物高效选择性分离Low亚群的研究 丰富的血浆蛋白。我们将以Ossabaw猪作为我们的模型来测试这种方法 系统，并将建立协议，最终将提供一种强大的方法，以任何基于生物流体 生物标志物的发现。我们建议将血浆蛋白质组作为喂食时间的函数来描述，并 与Ossabaw猪在此期间的生理和病理参数相关 患上代谢综合症。蛋白质组的发现正日益迫切而有力地推动着 到临床应用。这个项目基于一个独特的新概念，一旦开发出来，它将 极大地简化了程序并增强了我们敏感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，不仅是对 基于蛋白质组学的生物标志物发现的新工具的开发，但也朝着改进的方向发展 疾病治疗和促进更有效的诊断。

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.