Τίτλος:
Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2017 The Author(s).
Συγγραφείς:
Krochmal, M.
Cisek, K.
Filip, S.
Markoska, K.
Orange, C.
Zoidakis, J.
Gakiopoulou, C.
Spasovski, G.
Mischak, H.
Delles, C.
Vlahou, A.
Jankowski, J.
Περιοδικό:
Scientific Reports
Εκδότης:
Nature Publishing Group
Λέξεις-κλειδιά:
CAP1 protein, human; carboxypeptidase; cell cycle protein; cytoskeleton protein; lysosomal Pro-X carboxypeptidase; SHC transforming protein 1; SHC1 protein, human, case control study; data mining; female; gene expression profiling; gene regulatory network; genetics; human; immunoglobulin A nephropathy; kidney; male; metabolism; procedures; protein analysis; protein database; proteomics; tissue distribution; urine, Carboxypeptidases; Case-Control Studies; Cell Cycle Proteins; Cytoskeletal Proteins; Data Mining; Databases, Protein; Female; Gene Expression Profiling; Gene Regulatory Networks; Glomerulonephritis, IGA; Humans; Kidney; Male; Protein Interaction Maps; Proteomics; Src Homology 2 Domain-Containing, Transforming Protein 1; Tissue Distribution
DOI:
10.1038/s41598-017-09393-w
