Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis
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-...
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doaj-c72f1e532e7b496a8bf240ac7ab005b42020-12-08T01:08:45ZengNature Publishing GroupScientific Reports2045-23222017-08-017111310.1038/s41598-017-09393-wIdentification of novel molecular signatures of IgA nephropathy through an integrative -omics analysisMagdalena Krochmal0Katryna Cisek1Szymon Filip2Katerina Markoska3Clare Orange4Jerome Zoidakis5Chara Gakiopoulou6Goce Spasovski7Harald Mischak8Christian Delles9Antonia Vlahou10Joachim Jankowski11Biomedical Research Foundation Academy of Athens, Center of Basic ResearchMosaiques Diagnostics GmbHBiomedical Research Foundation Academy of Athens, Center of Basic ResearchDepartment of Nephrology, Medical Faculty, University of SkopjeDepartment of Pathology, School of Medicine, University of GlasgowBiomedical Research Foundation Academy of Athens, Center of Basic ResearchPathology Department, National and Kapodistrian University of AthensDepartment of Nephrology, Medical Faculty, University of SkopjeMosaiques Diagnostics GmbHInstitute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University PlaceBiomedical Research Foundation Academy of Athens, Center of Basic ResearchRWTH Aachen University Hospital, Institute for Molecular Cardiovascular ResearchAbstract 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.https://doi.org/10.1038/s41598-017-09393-w |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Magdalena Krochmal Katryna Cisek Szymon Filip Katerina Markoska Clare Orange Jerome Zoidakis Chara Gakiopoulou Goce Spasovski Harald Mischak Christian Delles Antonia Vlahou Joachim Jankowski |
spellingShingle |
Magdalena Krochmal Katryna Cisek Szymon Filip Katerina Markoska Clare Orange Jerome Zoidakis Chara Gakiopoulou Goce Spasovski Harald Mischak Christian Delles Antonia Vlahou Joachim Jankowski Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis Scientific Reports |
author_facet |
Magdalena Krochmal Katryna Cisek Szymon Filip Katerina Markoska Clare Orange Jerome Zoidakis Chara Gakiopoulou Goce Spasovski Harald Mischak Christian Delles Antonia Vlahou Joachim Jankowski |
author_sort |
Magdalena Krochmal |
title |
Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis |
title_short |
Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis |
title_full |
Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis |
title_fullStr |
Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis |
title_full_unstemmed |
Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis |
title_sort |
identification of novel molecular signatures of iga nephropathy through an integrative -omics analysis |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-08-01 |
description |
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. |
url |
https://doi.org/10.1038/s41598-017-09393-w |
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