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2015 ; 3
(ä): e1284
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Nodes with high centrality in protein interaction networks are responsible for
driving signaling pathways in diabetic nephropathy
#MMPMID26557424
Abedi M
; Gheisari Y
PeerJ
2015[]; 3
(ä): e1284
PMID26557424
show ga
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.