Challenges in translating plasma proteomics from bench to bedside: update from the NHLBI Clinical Proteomics Programs
Challenges in translating plasma proteomics from bench to bedside: update from the NHLBI Clinical Proteomics Programs
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DOI：
10.1152/ajplung.00044.2008
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发表时间：
2008-07-01
影响因子：
4.9
通讯作者：
Ware, Lorraine B.
中科院分区：
文献类型：
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作者：
Gerszten, Robert E.;Accurso, Frank;Ware, Lorraine B.
蛋白质组学的新兴科学领域包括全细胞、组织或体液的蛋白质含量或蛋白质组的鉴定、表征和定量。蛋白质组学技术鉴定和定量血浆中可用作临床疾病状态的存在或严重程度的生物标志物的新型蛋白质的潜力为临床应用带来了巨大希望。然而，在将血浆蛋白质组学从实验室转化为临床应用方面存在许多挑战，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转化为常规临床应用。这种翻译的关键障碍包括需要“正交”生物标志物（即，与现有标记物不相关）、生物样品中蛋白质组的复杂性、生物样品中存在高丰度蛋白质（例如白蛋白）阻碍低丰度蛋白质的检测、与高维数据集分析发生的假阳性关联以及对生长、发育和年龄对正常血浆蛋白质组的影响的有限理解。讨论了克服这些挑战的战略。
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.