Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease
Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease
复制标题
DOI：
10.1074/mcp.m110.001917
复制
发表时间：
2010-11-01
影响因子：
7
通讯作者：
Schmitt-Kopplin, Philippe
中科院分区：
文献类型：
--
作者：
Good, David M.;Zuerbig, Petra;Schmitt-Kopplin, Philippe
由于其可用性，易于收集，以及与生理学和病理学的相关性，尿液是临床蛋白质组学/肽组学的有吸引力的来源。然而，缺乏来自大型队列的可比数据集极大地阻碍了临床蛋白质组学的发展。在这里，我们报告建立一个可重复的，高分辨率的方法，用于肽组分析的天然存在的人尿肽和蛋白质，范围从800至17,000 Da，使用样品从3,600个人分析毛细管电泳耦合到MS。所有处理后的数据存储在结构化查询语言（SQL）数据库。该数据库目前包含5，010种相关的独特尿肽，可作为诊断和监测各种疾病的潜在分类器库。例如，通过使用这种信息来源，我们能够定义慢性肾脏疾病的尿肽生物标志物，从而能够高准确性地诊断这些疾病。在随后的复制阶段将慢性肾脏疾病特异性生物标志物集应用于独立的测试队列，导致85.5%的灵敏度和100%的特异性。这些结果表明，毛细管电泳耦合MS的潜在用途的临床应用中分析天然存在的尿肽。Molecular & Cellular Proteomics 9：2424-2437，2010.
Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides. Molecular & Cellular Proteomics 9:2424-2437, 2010.