Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis

Krochmal, M. et al. (2017) Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis. Scientific Reports, 7, 9091. (doi: 10.1038/s41598-017-09393-w) (PMID:28831120) (PMCID:PMC5567309)

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IgA nephropathy (IgAN) is the most prevalent among primary glomerular diseases worldwide. Although our understanding of IgAN has advanced significantly, its underlying biology and potential drug targets are still unexplored. We investigated a combinatorial approach for the analysis of IgAN-relevant -omics data, aiming at identification of novel molecular signatures of the disease. Nine published urinary proteomics datasets were collected and the reported differentially expressed proteins in IgAN vs. healthy controls were integrated into known biological pathways. Proteins participating in these pathways were subjected to multi-step assessment, including investigation of IgAN transcriptomics datasets (Nephroseq database), their reported protein-protein interactions (STRING database), kidney tissue expression (Human Protein Atlas) and literature mining. Through this process, from an initial dataset of 232 proteins significantly associated with IgAN, 20 pathways were predicted, yielding 657 proteins for further analysis. Step-wise evaluation highlighted 20 proteins of possibly high relevance to IgAN and/or kidney disease. Experimental validation of 3 predicted relevant proteins, adenylyl cyclase-associated protein 1 (CAP1), SHC-transforming protein 1 (SHC1) and prolylcarboxypeptidase (PRCP) was performed by immunostaining of human kidney sections. Collectively, this study presents an integrative procedure for -omics data exploitation, giving rise to biologically relevant results.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Orange, Miss Clare and Delles, Professor Christian and Mischak, Professor Harald
Authors: Krochmal, M., Cisek, K., Filip, S., Markoska, K., Orange, C., Zoidakis, J., Gakiopoulou, C., Spasovski, G., Mischak, H., Delles, C., Vlahou, A., and Jankowski, J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Scientific Reports 7(1):9091
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
637441IMODE-CKD: Clinical and system-omics for the identification of the Molecular Determinants of established Chronic Kidney DiseaseHolger HusiEuropean Commission (EC)608332RI CARDIOVASCULAR & MEDICAL SCIENCES