Nodes with high centrality in protein interaction networks are responsible for driving signaling pathways in diabetic nephropathy

In spite of huge efforts, chronic diseases remain an unresolved problem in medicine. Systems biology could assist to develop more efficient therapies through providing quantitative holistic sights to these complex disorders. In this study, we have re-analyzed a microarray dataset to identify critica...

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Main Authors: Maryam Abedi, Yousof Gheisari
Format: Article
Language:English
Published: PeerJ Inc. 2015-10-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/1284.pdf
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author Maryam Abedi
Yousof Gheisari
author_facet Maryam Abedi
Yousof Gheisari
author_sort Maryam Abedi
collection DOAJ
description In spite of huge efforts, chronic diseases remain an unresolved problem in medicine. Systems biology could assist to develop more efficient therapies through providing quantitative holistic sights to these complex disorders. In this study, we have re-analyzed a microarray dataset to identify critical signaling pathways related to diabetic nephropathy. GSE1009 dataset was downloaded from Gene Expression Omnibus database and the gene expression profile of glomeruli from diabetic nephropathy patients and those from healthy individuals were compared. The protein-protein interaction network for differentially expressed genes was constructed and enriched. In addition, topology of the network was analyzed to identify the genes with high centrality parameters and then pathway enrichment analysis was performed. We found 49 genes to be variably expressed between the two groups. The network of these genes had few interactions so it was enriched and a network with 137 nodes was constructed. Based on different parameters, 34 nodes were considered to have high centrality in this network. Pathway enrichment analysis with these central genes identified 62 inter-connected signaling pathways related to diabetic nephropathy. Interestingly, the central nodes were more informative for pathway enrichment analysis compared to all network nodes and also 49 differentially expressed genes. In conclusion, we here show that central nodes in protein interaction networks tend to be present in pathways that co-occur in a biological state. Also, this study suggests a computational method for inferring underlying mechanisms of complex disorders from raw high-throughput data.
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spelling doaj.art-204fb1bbe2ec43099feebda40629b6422023-12-03T10:56:49ZengPeerJ Inc.PeerJ2167-83592015-10-013e128410.7717/peerj.1284Nodes with high centrality in protein interaction networks are responsible for driving signaling pathways in diabetic nephropathyMaryam Abedi0Yousof Gheisari1Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, IranDepartment of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, IranIn spite of huge efforts, chronic diseases remain an unresolved problem in medicine. Systems biology could assist to develop more efficient therapies through providing quantitative holistic sights to these complex disorders. In this study, we have re-analyzed a microarray dataset to identify critical signaling pathways related to diabetic nephropathy. GSE1009 dataset was downloaded from Gene Expression Omnibus database and the gene expression profile of glomeruli from diabetic nephropathy patients and those from healthy individuals were compared. The protein-protein interaction network for differentially expressed genes was constructed and enriched. In addition, topology of the network was analyzed to identify the genes with high centrality parameters and then pathway enrichment analysis was performed. We found 49 genes to be variably expressed between the two groups. The network of these genes had few interactions so it was enriched and a network with 137 nodes was constructed. Based on different parameters, 34 nodes were considered to have high centrality in this network. Pathway enrichment analysis with these central genes identified 62 inter-connected signaling pathways related to diabetic nephropathy. Interestingly, the central nodes were more informative for pathway enrichment analysis compared to all network nodes and also 49 differentially expressed genes. In conclusion, we here show that central nodes in protein interaction networks tend to be present in pathways that co-occur in a biological state. Also, this study suggests a computational method for inferring underlying mechanisms of complex disorders from raw high-throughput data.https://peerj.com/articles/1284.pdfDiabetic nephropathyMicroarray analysisProtein interaction mapsSystems biology
spellingShingle Maryam Abedi
Yousof Gheisari
Nodes with high centrality in protein interaction networks are responsible for driving signaling pathways in diabetic nephropathy
PeerJ
Diabetic nephropathy
Microarray analysis
Protein interaction maps
Systems biology
title Nodes with high centrality in protein interaction networks are responsible for driving signaling pathways in diabetic nephropathy
title_full Nodes with high centrality in protein interaction networks are responsible for driving signaling pathways in diabetic nephropathy
title_fullStr Nodes with high centrality in protein interaction networks are responsible for driving signaling pathways in diabetic nephropathy
title_full_unstemmed Nodes with high centrality in protein interaction networks are responsible for driving signaling pathways in diabetic nephropathy
title_short Nodes with high centrality in protein interaction networks are responsible for driving signaling pathways in diabetic nephropathy
title_sort nodes with high centrality in protein interaction networks are responsible for driving signaling pathways in diabetic nephropathy
topic Diabetic nephropathy
Microarray analysis
Protein interaction maps
Systems biology
url https://peerj.com/articles/1284.pdf
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