scholarly journals Network Cluster Analysis of Protein–Protein Interaction Network–Identified Biomarker for Type 2 Diabetes

2015 ◽  
Vol 17 (7) ◽  
pp. 475-481 ◽  
Author(s):  
Zhonghui Li ◽  
Zijun Qiao ◽  
Wenling Zheng ◽  
Wenli Ma
Keyword(s):  
Type 2 Diabetes ◽  
Cluster Analysis ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Protein Protein Interaction ◽  
Network Cluster ◽  
Protein Protein Interaction Network

Exploring Shared Pathogenesis of Alzheimer’s Disease and Type 2 Diabetes Mellitus via Co-expression Networks Analysis

2020 ◽  
Vol 17 (6) ◽  
pp. 566-575 ◽  
Author(s):  
Yukun Zhu ◽  
Xuelu Ding ◽  
Zhaoyuan She ◽  
Xue Bai ◽  
Ziyang Nie ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Protein Protein Interaction Network

Background: Alzheimer’s Disease (AD) and Type 2 Diabetes Mellitus (T2DM) have an increased incidence in modern society. Although increasing evidence has supported the close linkage between these two disorders, the inter-relational mechanisms remain to be fully elucidated. Objective: The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and T2DM. Methods: We downloaded the microarray data of AD and T2DM from the Gene Expression Omnibus (GEO) database and constructed co-expression networks by Weighted Gene Co-Expression Network Analysis (WGCNA) to identify gene network modules related to AD and T2DM. Then, Gene Ontology (GO) and pathway enrichment analysis were performed on the common genes existing in the AD and T2DM related modules by clusterProfiler and DOSE package. Finally, we utilized the STRING database to construct the protein-protein interaction network and found out the hub genes in the network. Results: Our findings indicated that seven and four modules were the most significant with AD and T2DM, respectively. Functional enrichment analysis showed that AD and T2DM common genes were mainly enriched in signaling pathways such as circadian entrainment, phagosome, glutathione metabolism and synaptic vesicle cycle. Protein-protein interaction network construction identified 10 hub genes (CALM1, LRRK2, RBX1, SLC6A1, TXN, SNRPF, GJA1, VWF, LPL, AGT) in AD and T2DM shared genes. Conclusions: Our work identified common pathogenesis of AD and T2DM. These shared pathways might provide a novel idea for further mechanistic studies and hub genes that may serve as novel therapeutic targets for diagnosis and treatment of AD and T2DM.

scholarly journals Developing a network view of type 2 diabetes risk pathways through integration of genetic, genomic and functional data

2018 ◽  
Author(s):  
Juan Fernéndez-Tajes ◽  
Kyle J Gaulton ◽  
Martijn van de Bunt ◽  
Jason Torres ◽  
Matthias Thurner ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Functional Connectivity ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Seed Proteins ◽  
Interaction Network ◽  
Biological Processes ◽  
Protein Protein Interaction

AbstractGenome wide association studies (GWAS) have identified several hundred susceptibility loci for Type 2 Diabetes (T2D). One critical, but unresolved, issue concerns the extent to which the mechanisms through which these diverse signals influencing T2D predisposition converge on a limited set of biological processes. However, the causal variants identified by GWAS mostly fall into non-coding sequence, complicating the task of defining the effector transcripts through which they operate. Here, we describe implementation of an analytical pipeline to address this question. First, we integrate multiple sources of genetic, genomic, and biological data to assign positional candidacy scores to the genes that map to T2D GWAS signals. Second, we introduce genes with high scores as seeds within a network optimization algorithm (the asymmetric prize-collecting Steiner Tree approach) which uses external, experimentally-confirmed protein-protein interaction (PPI) data to generate high confidence subnetworks. Third, we use GWAS data to test the T2D-association enrichment of the “non-seed” proteins introduced into the network, as a measure of the overall functional connectivity of the network. We find: (a) non-seed proteins in the T2D protein-interaction network so generated (comprising 705 nodes) are enriched for association to T2D (p=0.0014) but not control traits; (b) stronger T2D-enrichment for islets than other tissues when we use RNA expression data to generate tissue-specific PPI networks; and (c) enhanced enrichment (p=3.9×l0−5) when we combine analysis of the islet-specific PPI network with a focus on the subset of T2D GWAS loci which act through defective insulin secretion. These analyses reveal a pattern of non-random functional connectivity between causal candidate genes atT2D GWAS loci, and highlight the products of genes including YWHAG, SMAD4 or CDK2 as contributors to T2D-relevant islet dysfunction. The approach we describe can be applied to other complex genetic and genomic data sets, facilitating integration of diverse data types into disease-associated networks.Author summaryWe were interested in the following question: as we discover more and more genetic variants associated with a complex disease, such as type 2 diabetes, will the biological pathways implicated by those variants proliferate, or will the biology converge onto a more limited set of aetiological processes? To address this, we first took the 1895 genes that map to ~100 type 2 diabetes association signals, and pruned these to a set of 451 for which combined genetic, genomic and biological evidence assigned the strongest candidacy with respect to type 2 diabetes pathogenesis. We then sought to maximally connect these genes within a curated protein-protein interaction network. We found that proteins brought into the resulting diabetes interaction network were themselves enriched for diabetes association signals as compared to appropriate control proteins. Furthermore, when we used tissue-specific RNA abundance data to filter the generic protein-protein network, we found that the enrichment for type 2 diabetes association signals was enhanced within a network filtered for pancreatic islet expression, particularly when we selected the subset of diabetes association signals acting through reduced insulin secretion. Our data demonstrate convergence of the biological processes involved in type 2 diabetes pathogenesis and highlight novel contributors.

scholarly journals Diabetic Retinopathy and Laser Therapy in Rats: A Protein-Protein Interaction Network Analysis

2017 ◽  
Vol 8 (Suppl 1) ◽  
pp. S20-S21 ◽  
Author(s):  
Akram Safaei ◽  
Mostafa Rezaei Tavirani ◽  
Mona Zamanian Azodi ◽  
Alireza Lashay ◽  
Seyed Farzad Mohammadi ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Network Analysis ◽  
Laser Therapy ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Protein Protein Interaction ◽  
Protein Protein Interaction Network
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