ProteoSys AG, Mainz, Germany.
Ann N Y Acad Sci. 2010 Jun;1197:118-28. doi: 10.1111/j.1749-6632.2009.05395.x.
There is an urgent need for surrogate biomarkers in clinical diagnostics but also preclinical in toxicology of chemicals and efficacy testing of pharmaceuticals. On the background of the emerging fields of systems biology and theranostics, the importance of time scales and the synchronization of complex biological readouts become increasingly obvious. Systemic effects such as responses to stimuli, medical intervention, cellular stress, or toxicity elicit immediate molecular changes on the protein level. Early events include phosphorylation and oxidation of proteins. These posttranslational modifications have a direct impact on enzyme activities and protein-protein interactions. Only at downstream stages is gene transcription activated. Here we outline the analytical and statistical requirements dealing with complex patterns of protein expression and the extraction of protein surrogate biomarkers defining specific early stages of biological responses. We also present successful examples from research on aging and discuss prerequisites and necessary considerations while moving candidates to validation.
临床诊断以及化学品毒理学和药物疗效测试的临床前研究都迫切需要替代生物标志物。在系统生物学和治疗诊断学等新兴领域的背景下，时间尺度的重要性以及复杂生物读数的同步性变得越来越明显。诸如对刺激、医学干预、细胞应激或毒性的反应等全身效应会在蛋白质水平上立即引发分子变化。早期事件包括蛋白质的磷酸化和氧化。这些翻译后修饰直接影响酶活性和蛋白质-蛋白质相互作用。只有在下游阶段基因转录才会被激活。在这里，我们概述了处理复杂蛋白质表达模式以及提取定义生物反应特定早期阶段的蛋白质替代生物标志物的分析和统计要求。我们还展示了衰老研究中的成功案例，并讨论了将候选物推进到验证阶段的先决条件和必要考虑因素。
