Identification of key gene pathways and coexpression networks of islets in human type 2 diabetes

Lu Li,1,* Zongfu Pan,2,* Si Yang,1 Wenya Shan,1 Yanyan Yang1 1Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People&r...

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Autores principales:	Li L, Pan Z, Yang S, Shan W, Yang Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	type 2 diabetes islet β cell bioinformatics analysis differentially expressed genes WGCNA Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/274e4ee9f27d4349b79fcc9480d589da
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spelling	oai:doaj.org-article:274e4ee9f27d4349b79fcc9480d589da2021-12-02T01:56:19ZIdentification of key gene pathways and coexpression networks of islets in human type 2 diabetes1178-7007https://doaj.org/article/274e4ee9f27d4349b79fcc9480d589da2018-09-01T00:00:00Zhttps://www.dovepress.com/identification-of-key-gene-pathways-and-co-expression-networks-of-isle-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Lu Li,1,* Zongfu Pan,2,* Si Yang,1 Wenya Shan,1 Yanyan Yang1 1Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China *These authors contributed equally to this work Purpose: The number of people with type 2 diabetes (T2D) is growing rapidly worldwide. Islet β-cell dysfunction and failure are the main causes of T2D pathological processes. The aim of this study was to elucidate the underlying pathways and coexpression networks in T2D islets. Materials and methods: We analyzed the differentially expressed genes (DEGs) in the data set GSE41762, which contained 57 nondiabetic and 20 diabetic samples, and developed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein–protein interaction (PPI) network, the modules from the PPI network, and the gene annotation enrichment of modules were analyzed as well. Moreover, a weighted correlation network analysis (WGCNA) was applied to screen critical gene modules and coexpression networks and explore the biological significance. Results: We filtered 957 DEGs in T2D islets. Then GO and KEGG analyses identified that key pathways like inflammatory response, type B pancreatic cell differentiation, and calcium ion-dependent exocytosis were involved in human T2D. Three significant modules were filtered from the PPI network. Ribosome biogenesis, extrinsic apoptotic signaling pathway, and membrane depolarization during action potential were associated with the modules, respectively. Furthermore, coexpression network analysis by WGCNA identified 13 distinct gene modules of T2D islets and revealed four modules, which were strongly correlated with T2D and T2D biomarker hemoglobin A1c (HbA1c). Functional annotation showed that these modules mainly enriched KEGG pathways such as NF-kappa B signaling pathway, tumor necrosis factor signaling pathway, cyclic adenosine monophosphate signaling pathway, and peroxisome proliferators-activated receptor signaling pathway. Conclusion: The results provide potential gene pathways and underlying molecular mechanisms for the prevention, diagnosis, and treatment of T2D. Keywords: type 2 diabetes, islet β cell, bioinformatics analysis, differentially expressed genes, WGCNALi LPan ZYang SShan WYang YDove Medical Pressarticletype 2 diabetesislet β cellbioinformatics analysisdifferentially expressed genesWGCNASpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 11, Pp 553-563 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	type 2 diabetes islet β cell bioinformatics analysis differentially expressed genes WGCNA Specialties of internal medicine RC581-951
spellingShingle	type 2 diabetes islet β cell bioinformatics analysis differentially expressed genes WGCNA Specialties of internal medicine RC581-951 Li L Pan Z Yang S Shan W Yang Y Identification of key gene pathways and coexpression networks of islets in human type 2 diabetes
description	Lu Li,1,* Zongfu Pan,2,* Si Yang,1 Wenya Shan,1 Yanyan Yang1 1Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China *These authors contributed equally to this work Purpose: The number of people with type 2 diabetes (T2D) is growing rapidly worldwide. Islet β-cell dysfunction and failure are the main causes of T2D pathological processes. The aim of this study was to elucidate the underlying pathways and coexpression networks in T2D islets. Materials and methods: We analyzed the differentially expressed genes (DEGs) in the data set GSE41762, which contained 57 nondiabetic and 20 diabetic samples, and developed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein–protein interaction (PPI) network, the modules from the PPI network, and the gene annotation enrichment of modules were analyzed as well. Moreover, a weighted correlation network analysis (WGCNA) was applied to screen critical gene modules and coexpression networks and explore the biological significance. Results: We filtered 957 DEGs in T2D islets. Then GO and KEGG analyses identified that key pathways like inflammatory response, type B pancreatic cell differentiation, and calcium ion-dependent exocytosis were involved in human T2D. Three significant modules were filtered from the PPI network. Ribosome biogenesis, extrinsic apoptotic signaling pathway, and membrane depolarization during action potential were associated with the modules, respectively. Furthermore, coexpression network analysis by WGCNA identified 13 distinct gene modules of T2D islets and revealed four modules, which were strongly correlated with T2D and T2D biomarker hemoglobin A1c (HbA1c). Functional annotation showed that these modules mainly enriched KEGG pathways such as NF-kappa B signaling pathway, tumor necrosis factor signaling pathway, cyclic adenosine monophosphate signaling pathway, and peroxisome proliferators-activated receptor signaling pathway. Conclusion: The results provide potential gene pathways and underlying molecular mechanisms for the prevention, diagnosis, and treatment of T2D. Keywords: type 2 diabetes, islet β cell, bioinformatics analysis, differentially expressed genes, WGCNA
format	article
author	Li L Pan Z Yang S Shan W Yang Y
author_facet	Li L Pan Z Yang S Shan W Yang Y
author_sort	Li L
title	Identification of key gene pathways and coexpression networks of islets in human type 2 diabetes
title_short	Identification of key gene pathways and coexpression networks of islets in human type 2 diabetes
title_full	Identification of key gene pathways and coexpression networks of islets in human type 2 diabetes
title_fullStr	Identification of key gene pathways and coexpression networks of islets in human type 2 diabetes
title_full_unstemmed	Identification of key gene pathways and coexpression networks of islets in human type 2 diabetes
title_sort	identification of key gene pathways and coexpression networks of islets in human type 2 diabetes
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/274e4ee9f27d4349b79fcc9480d589da
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_version_	1718402763374723072

Identification of key gene pathways and coexpression networks of islets in human type 2 diabetes

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