期刊
MOLECULAR & CELLULAR PROTEOMICS
卷 9, 期 11, 页码 2424-2437出版社
ELSEVIER
DOI: 10.1074/mcp.M110.001917
关键词
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资金
- National Institutes of Health [DK067638, DK075868, DK078244, DK061525, DK080301, DK082753]
- Biotechnology Training Program Predoctoral Fellowship [5T32GM08349]
- Eurotransbio [ETB-2006-016]
- Lower Saxony Ministry of Economy [203.19-32329-5-461]
- InGenious HyperCare [LSHM-CT-2006-037093]
- British Heart Foundation [RG/02/012]
- Federal Ministry of Education and Research [NGFN/01GR0807]
- Biotechnology and Biological Sciences Research Council
- Engineering and Physical Sciences Research Council Interdisciplinary Research Collaboration in Proteomic Technology (IRColl) Grant Radical Solutions for Researching the Proteome (RASOR)
- Wellcome Trust [29240]
- INSERM
- Fondation pour la Recherche Medicale
- European Union Prevention of Diabetic Complications (PREDICTIONS) [LSHM-CT-2005-018733]
- European Union [LSHM-CT-2005-018733, HEALTH-F2-2009-241544]
- Engineering and Physical Sciences Research Council [EP/E052029/2] Funding Source: researchfish
- Medical Research Council [G0401466] Funding Source: researchfish
- EPSRC [EP/E052029/2] Funding Source: UKRI
- MRC [G0401466] Funding Source: UKRI
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.
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