Farrah Terry, Deutsch Eric W, Omenn Gilbert S, Sun Zhi, Watts Julian D, Yamamoto Tadashi, Shteynberg David, Harris Micheleen M, Moritz Robert L
J Proteome Res. 2014 Jan 3;13(1):60-75. doi: 10.1021/pr4010037. Epub 2013 Dec 6.
The kidney, urine, and plasma proteomes are intimately related: proteins and metabolic waste products are filtered from the plasma by the kidney and excreted via the urine, while kidney proteins may be secreted into the circulation or released into the urine. Shotgun proteomics data sets derived from human kidney, urine, and plasma samples were collated and processed using a uniform software pipeline, and relative protein abundances were estimated by spectral counting. The resulting PeptideAtlas builds yielded 4005, 2491, and 3553 nonredundant proteins at 1% FDR for the kidney, urine, and plasma proteomes, respectively - for kidney and plasma, the largest high-confidence protein sets to date. The same pipeline applied to all available human data yielded a 2013 Human PeptideAtlas build containing 12,644 nonredundant proteins and at least one peptide for each of ∼14,000 Swiss-Prot entries, an increase over 2012 of ∼7.5% of the predicted human proteome. We demonstrate that abundances are correlated between plasma and urine, examine the most abundant urine proteins not derived from either plasma or kidney, and consider the biomarker potential of proteins associated with renal decline. This analysis forms part of the Biology and Disease-driven Human Proteome Project (B/D-HPP) and is a contribution to the Chromosome-centric Human Proteome Project (C-HPP) special issue.
肾脏、尿液和血浆蛋白质组密切相关:蛋白质和代谢废物由肾脏从血浆中滤过并经尿液排出,而肾脏蛋白质可能分泌入血液循环或释放到尿液中。来自人类肾脏、尿液和血浆样本的鸟枪法蛋白质组学数据集使用统一的软件流程进行整理和处理,并通过光谱计数估计相对蛋白质丰度。所得的肽图集分别为肾脏、尿液和血浆蛋白质组在1%错误发现率下产生了4005、2491和3553个非冗余蛋白质——对于肾脏和血浆而言,这是迄今为止最大的高可信度蛋白质集。将相同流程应用于所有可用的人类数据,得到了一个2013年的人类肽图集版本,包含12,644个非冗余蛋白质,并且对于约14,000个瑞士蛋白质数据库条目均至少有一个肽段,相较于2012年增加了约7.5%的预测人类蛋白质组。我们证明了血浆和尿液中的丰度具有相关性,研究了并非源自血浆或肾脏的最丰富的尿液蛋白质,并考虑了与肾脏功能衰退相关蛋白质的生物标志物潜力。该分析是生物学和疾病驱动的人类蛋白质组计划(B/D-HPP)的一部分,也是对以染色体为中心的人类蛋白质组计划(C-HPP)特刊的一项贡献。