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

Magdalena Krochmal, Katryna Cisek, Szymon Filip, Katerina Markoska, Clare Orange, Jerome Zoidakis, Chara Gakiopoulou, Goce Spasovski, Harald Mischak, Christian Delles, Antonia Vlahou*, Joachim Jankowski*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Web of Science)

Abstract

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.

Original languageEnglish
Article number9091
Number of pages13
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 22 Aug 2017

Keywords

  • CHRONIC KIDNEY-DISEASE
  • IMMUNOGLOBULIN-A NEPHROPATHY
  • GALACTOSE-DEFICIENT IGA1
  • TYROSINE-PHOSPHATASE 1B
  • CHRONIC RENAL-DISEASE
  • NEGATIVE REGULATOR
  • PROTEOMIC ANALYSIS
  • OXIDATIVE STRESS
  • PODOCYTE INJURY
  • ACE-INHIBITORS

Cite this