Science for Life Laboratory, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Solna, Sweden.
Department of Clinical Medicine, Faculty of Health Science, The Arctic University of Tromsø, Tromsø, Norway.
Methods Mol Biol. 2021;2344:163-179. doi: 10.1007/978-1-0716-1562-1_12.
Systematic exploration of the dynamic human plasma proteome enables the discovery of novel protein biomarkers. Using state-of-the-art technologies holds the promise to facilitate a better diagnosis and risk prediction of diseases. Cardiovascular disease (CVD) pathophysiology is characterized for unbalancing of processes such as vascular inflammation, endothelial dysfunction, or lipid profiles among others. Such processes have a direct impact on the dynamic and complex composition of blood and hence the plasma proteome. Therefore, the study of the plasma proteome comprises an excellent exploratory source of biomarker research particularly for CVD. We describe the protocol for performing the discovery of protein biomarker candidates using the suspension bead array technology. The process does not require depletion steps to remove abundant proteins and consumes only a few microliters of sample from the body fluid of interest. The approach is scalable to measure many analytes as well as large numbers of samples. Moreover, we describe a bead-assisted antibody-labeling process that helps to develop quantitative assays for validation purposes and facilitate the translation of the identified candidates into clinical studies.
系统探索人类血浆蛋白质组的动态变化能够发现新的蛋白质生物标志物。利用最先进的技术有望更好地诊断和预测疾病的风险。心血管疾病 (CVD) 的病理生理学特征是血管炎症、内皮功能障碍或脂质谱等过程失去平衡。这些过程直接影响血液的动态和复杂组成,因此血浆蛋白质组学是一个很好的探索性生物标志物研究来源,特别是对于 CVD。我们描述了使用悬浮珠阵列技术发现蛋白质生物标志物候选物的方案。该过程不需要进行耗竭步骤来去除丰富的蛋白质,仅需要从感兴趣的体液中消耗几微升的样本。该方法可扩展到测量许多分析物以及大量的样本。此外,我们还描述了一种珠辅助的抗体标记过程,有助于开发定量测定方法用于验证目的,并促进将鉴定出的候选物转化为临床研究。