特异性生物标记物的发现有益于疾病的早期诊断,促进靶向治疗的发展,并提供精确的治疗反应监控方法。血浆中候选生物标记物的验证过程中的一个主要问题是血浆中蛋白质浓度的动态范围非常广。本文回顾了当前能够在所预期的血浆浓度范围内(如ng/ml浓度水平)量化候选生物标记物的定向蛋白质组学策略。另外,提供了基于定向质谱法,可对大部分候选生物标记蛋白进行快速验证的技术流程。这些公开数据库中的技术对生物标记的验证研究中的处理量具有极大影响潜力。%The identification of specific biomarkers will improve the early diagnosis of disease, facilitate the development of targeted therapies, and provide an accurate method to monitor treatment response. A major challenge in the process of verifying biomarker candidates in blood plasma is the complexity and high dynamic range of proteins. This article reviews the current, targeted proteomic strategies that are capable of quantifying biomarker candidates at concentration ranges where biomarkers are expected in plasma (i.e. at the ng/ml level). In addition, a workflow is presented that allows the fast and definitive generation of targeted mass spectrometry-based assays for most biomarker candidate proteins. These assays are stored in publicly accessible databases and have the potential to greatly impact the throughput of biomarker verification studies.
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