Nedelkov Dobrin, Kiernan Urban A, Niederkofler Eric E, Tubbs Kemmons A, Nelson Randall W
Intrinsic Bioprobes, Inc., Tempe, Arizona 85281, USA.
Mol Cell Proteomics. 2006 Oct;5(10):1811-8. doi: 10.1074/mcp.R600006-MCP200. Epub 2006 May 30.
This review outlines the concept of population proteomics and its implication in the discovery and validation of cancer-specific protein modulations. Population proteomics is an applied subdiscipline of proteomics engaging in the investigation of human proteins across and within populations to define and better understand protein diversity. Population proteomics focuses on interrogation of specific proteins from large number of individuals, utilizing top-down, targeted affinity mass spectrometry approaches to probe protein modifications. Deglycosylation, sequence truncations, side-chain residue modifications, and other modifications have been reported for myriad of proteins, yet little is know about their incidence rate in the general population. Such information can be gathered via population proteomics and would greatly aid the biomarker discovery efforts. Discovery of novel protein modifications is also expected from such large scale population proteomics, expanding the protein knowledge database. In regard to cancer protein biomarkers, their validation via population proteomics-based approaches is advantageous as mass spectrometry detection is used both in the discovery and validation process, which is essential for the detection of those structurally modified protein biomarkers.
本综述概述了群体蛋白质组学的概念及其在癌症特异性蛋白质调控的发现和验证中的意义。群体蛋白质组学是蛋白质组学的一个应用子学科,致力于研究不同人群和人群内部的人类蛋白质,以定义并更好地理解蛋白质多样性。群体蛋白质组学专注于对大量个体的特定蛋白质进行分析,利用自上而下的靶向亲和质谱方法来探究蛋白质修饰。已报道多种蛋白质存在去糖基化、序列截断、侧链残基修饰及其他修饰,但对其在普通人群中的发生率知之甚少。此类信息可通过群体蛋白质组学收集,这将极大地助力生物标志物的发现工作。通过这种大规模群体蛋白质组学,还有望发现新的蛋白质修饰,从而扩充蛋白质知识数据库。对于癌症蛋白质生物标志物而言,基于群体蛋白质组学的方法进行验证具有优势,因为在发现和验证过程中均使用质谱检测,这对于检测那些结构修饰的蛋白质生物标志物至关重要。