Statistical analysis of variation in the human plasma proteome.

Statistical analysis of variation in the human plasma proteome.
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DOI:
10.1155/2010/258494
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发表时间:
2010
影响因子:
--
通讯作者:
Chromy BA
Chromy BA
中科院分区:
其他
文献类型:
--
作者:
Corzett TH;Fodor IK;Choi MW;Walsworth VL;Turteltaub KW;McCutchen-Maloney SL;Chromy BA

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定量人血浆蛋白质组的变异是疾病特异性生物标志物检测的必要前提。我们在这里报告的纵向和个人的变化,其特征在于在人血浆的二维差异凝胶电泳(2-D DIGE)使用血浆样本从11个健康受试者收集三次超过两周的时间。使用固定效应建模来去除染料和凝胶的可变性。然后使用混合效应模型来定量蛋白质组学变异的来源。受试者间变异代表最大的方差分量,而受试者内时间变异与先前技术变异性研究中发现的实验变异相当,其中一份人血浆样本平行处理8次,然后通过2-D DIGE一式三份分析每份样本。在这里,21个蛋白质点的CV大于50%,表明这些蛋白质可能不适合作为生物标志物,应在未来的研究中仔细检查。78个蛋白质点显示不同的个人或个人收藏品之间的差异蛋白质水平进行了鉴定,通过质谱和进一步的特点,使用分层聚类。这些结果为理解人血浆蛋白质组中纵向和个体变异的复杂性迈出了第一步,并为改进生物标志物的发现提供了基线。
Quantifying the variation in the human plasma proteome is an essential prerequisite for disease-specific biomarker detection. We report here on the longitudinal and individual variation in human plasma characterized by two-dimensional difference gel electrophoresis (2-D DIGE) using plasma samples from eleven healthy subjects collected three times over a two week period. Fixed-effects modeling was used to remove dye and gel variability. Mixed-effects modeling was then used to quantitate the sources of proteomic variation. The subject-to-subject variation represented the largest variance component, while the time-within-subject variation was comparable to the experimental variation found in a previous technical variability study where one human plasma sample was processed eight times in parallel and each was then analyzed by 2-D DIGE in triplicate. Here, 21 protein spots had larger than 50% CV, suggesting that these proteins may not be appropriate as biomarkers and should be carefully scrutinized in future studies. Seventy-eight protein spots showing differential protein levels between different individuals or individual collections were identified by mass spectrometry and further characterized using hierarchical clustering. The results present a first step toward understanding the complexity of longitudinal and individual variation in the human plasma proteome, and provide a baseline for improved biomarker discovery.
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影响因子: 3.4
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