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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Autores principales: Magdalena Krochmal, Katryna Cisek, Szymon Filip, Katerina Markoska, Clare Orange, Jerome Zoidakis, Chara Gakiopoulou, Goce Spasovski, Harald Mischak, Christian Delles, Antonia Vlahou, Joachim Jankowski
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/c72f1e532e7b496a8bf240ac7ab005b4
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spelling oai:doaj.org-article:c72f1e532e7b496a8bf240ac7ab005b42021-12-02T15:04:54ZIdentification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis10.1038/s41598-017-09393-w2045-2322https://doaj.org/article/c72f1e532e7b496a8bf240ac7ab005b42017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09393-whttps://doaj.org/toc/2045-2322Abstract 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.Magdalena KrochmalKatryna CisekSzymon FilipKaterina MarkoskaClare OrangeJerome ZoidakisChara GakiopoulouGoce SpasovskiHarald MischakChristian DellesAntonia VlahouJoachim JankowskiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
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.
format article
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
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 Portfolio
publishDate 2017
url https://doaj.org/article/c72f1e532e7b496a8bf240ac7ab005b4
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