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Challenges in translating plasma proteomics from bench to bedside: update from the NHLBI Clinical Proteomics Programs

机译:将血浆蛋白质组学从实验台转化为床旁的挑战:NHLBI临床蛋白质组学计划的最新动态

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摘要

The emerging scientific field of proteomics encompasses the identification, characterization, and quantification of the protein content or proteome of whole cells, tissues, or body fluids. The potential for proteomic technologies to identify and quantify novel proteins in the plasma that can function as biomarkers of the presence or severity of clinical disease states holds great promise for clinical use. However, there are many challenges in translating plasma proteomics from bench to bedside, and relatively few plasma biomarkers have successfully transitioned from proteomic discovery to routine clinical use. Key barriers to this translation include the need for “orthogonal” biomarkers (i.e., uncorrelated with existing markers), the complexity of the proteome in biological samples, the presence of high abundance proteins such as albumin in biological samples that hinder detection of low abundance proteins, false positive associations that occur with analysis of high dimensional datasets, and the limited understanding of the effects of growth, development, and age on the normal plasma proteome. Strategies to overcome these challenges are discussed.
机译:蛋白质组学的新兴科学领域包括对全细胞,组织或体液中蛋白质含量或蛋白质组的鉴定,表征和定量。蛋白质组学技术在血浆中鉴定和定量可作为临床疾病状态或严重程度生物标志物的新型蛋白质的潜力为临床应用带来了广阔前景。然而,将血浆蛋白质组学从实验台转化为床旁存在许多挑战,并且相对较少的血浆生物标志物已成功地从蛋白质组学发现过渡到常规临床应用。该翻译的主要障碍包括对“正交”生物标志物的需求(即与现有标志物不相关),生物样品中蛋白质组的复杂性,生物样品中高丰度蛋白(如白蛋白)的存在,这阻碍了对低丰度蛋白的检测。 ,与高维数据集的分析相关的假阳性关联,以及对正常血浆蛋白质组的生长,发育和年龄影响的有限了解。讨论了克服这些挑战的策略。

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