基于多重微阵列分析鉴定牙周炎相关的枢纽基因和转录因子。

Identification of hub genes and transcription factors involved in periodontitis on the basis of multiple microarray analysis.

机构信息

Shanghai Engineering Research Center of Tooth Restoration and Regeneration; Dept. of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tongji University, Shanghai 200072, China.

Shanghai Engineering Research Center of Tooth Restoration and Regeneration; Dept. of Prosthodontics, School and Hospital of Stomatology, Tongji University, Shanghai 200072, China.

出版信息

Hua Xi Kou Qiang Yi Xue Za Zhi. 2021 Dec 1;39(6):633-641. doi: 10.7518/hxkq.2021.06.003.

DOI:10.7518/hxkq.2021.06.003

PMID:34859622

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8703101/

Abstract

OBJECTIVES

To identify the differentially expressed genes (DEGs) during the pathogenesis of periodontitis by bioinformatics analysis.

METHODS

GEO2R was used to screen DEGs in GSE10334 and GSE16134. Then, the overlapped DEGs were used for further analysis. g:Profiler was used to perform Gene Ontology analysis and pathway analysis for upregulated and downregulated DEGs. The STRING database was used to construct the protein-protein interaction (PPI) network, which was further visua-lized and analyzed by Cytoscape software. Hub genes and key modules were identified by cytoHubba and MCODE plug-ins, respectively. Finally, transcription factors were predicted via iRegulon plug-in.

RESULTS

A total of 196 DEGs were identified, including 139 upregulated and 57 downregulated DEGs. Functional enrichment analysis showed that the upregulated DEGs were mainly enriched in immune-related pathways including immune system, viral protein interaction with cytokine and cytokine receptor, cytokine-cytokine receptor interaction, leukocyte transendothelial migration, and chemokine receptors bind chemokines. On the contrary, the downregulated DEGs were mainly related to the formation of the cornified envelope and keratinization. The identified hub genes in the PPI network were CXCL8, CXCL1, CXCR4, SEL, CD19, and IKZF1. The top three modules were involved in chemokine response, B cell receptor signaling pathway, and interleukin response, respectively. iRegulon analysis revealed that IRF4 scored the highest.

CONCLUSIONS

The pathogenesis of periodontitis was closely associated with the expression levels of the identified hub genes including CXCL8, CXCL1, CXCR4, SELL, CD19, and IKZF1. IRF4, the predicted transcription factor, might serve as a dominant upstream regulator.

摘要

目的

通过生物信息学分析鉴定牙周病发病机制中的差异表达基因（DEGs）。

方法

使用 GEO2R 筛选 GSE10334 和 GSE16134 中的 DEGs。然后，对重叠的 DEGs 进行进一步分析。使用 g:Profiler 对上调和下调的 DEGs 进行基因本体论分析和通路分析。使用 STRING 数据库构建蛋白质-蛋白质相互作用（PPI）网络，然后使用 Cytoscape 软件进行可视化和分析。使用 cytoHubba 和 MCODE 插件分别识别枢纽基因和关键模块。最后，通过 iRegulon 插件预测转录因子。

结果

共鉴定出 196 个 DEGs，包括 139 个上调 DEGs 和 57 个下调 DEGs。功能富集分析表明，上调的 DEGs 主要富集在免疫相关途径，包括免疫系统、病毒蛋白与细胞因子和细胞因子受体相互作用、细胞因子-细胞因子受体相互作用、白细胞穿越内皮迁移和趋化因子受体结合趋化因子。相反，下调的 DEGs 主要与角蛋白形成和角化有关。PPI 网络中鉴定的枢纽基因包括 CXCL8、CXCL1、CXCR4、SELL、CD19 和 IKZF1。排名前三的模块分别参与趋化因子反应、B 细胞受体信号通路和白细胞介素反应。iRegulon 分析表明，IRF4 得分最高。