通过加权相关网络分析鉴定杜氏肌营养不良症和贝克肌营养不良症的枢纽基因。
Identifying the hub genes for Duchenne muscular dystrophy and Becker muscular dystrophy by weighted correlation network analysis.
机构信息
Qingdao University, No.308, Ningxia Road, Qingdao, Shandong Province, 266000, China.
Orthopaedic Center, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, Shandong Province, 266000, China.
出版信息
BMC Genom Data. 2021 Dec 18;22(1):57. doi: 10.1186/s12863-021-01014-w.
BACKGROUND
The goal of this study is to identify the hub genes for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) via weighted correlation network analysis (WGCNA).
METHODS
The gene expression profile of vastus lateralis biopsy samples obtained in 17 patients with DMD, 11 patients with BMD and 6 healthy individuals was downloaded from the Gene Expression Omnibus (GEO) database (GSE109178). After obtaining different expressed genes (DEGs) via GEO2R, WGCNA was conducted using R package, modules and genes that highly associated with DMD, BMD, and their age or pathology were screened. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network analysis were also conducted. Hub genes and highly correlated clustered genes were identified using Search Tool for the Retrieval of Interacting Genes (STRING) and Cystoscape software.
RESULTS
One thousand four hundred seventy DEGs were identified between DMD and control, with 1281 upregulated and 189 downregulated DEGs. Four hundred and twenty DEGs were found between BMD and control, with 157 upregulated and 263 upregulated DEGs. Fourteen modules with different colors were identified for DMD vs control, and 7 modules with different colors were identified for BMD vs control. Ten hub genes were summarized for DMD and BMD respectively, 5 hub genes were summarized for BMD age, 5 and 3 highly correlated clustered genes were summarized for DMD age and BMD pathology, respectively. In addition, 20 GO enrichments were found to be involved in DMD, 3 GO enrichments were found to be involved in BMD, 3 GO enrichments were found to be involved in BMD age.
CONCLUSION
In DMD, several hub genes were identified: C3AR1, TLR7, IRF8, FYB and CD33(immune and inflammation associated genes), TYROBP, PLEK, AIF1(actin reorganization associated genes), LAPTM5 and NT5E(cell death and arterial calcification associated genes, respectively). In BMD, a number of hub genes were identified: LOX, ELN, PLEK, IKZF1, CTSK, THBS2, ADAMTS2, COL5A1(extracellular matrix associated genes), BCL2L1 and CDK2(cell cycle associated genes).
背景
本研究旨在通过加权相关网络分析（WGCNA）鉴定杜氏肌营养不良症（DMD）和贝克肌营养不良症（BMD）的枢纽基因。
方法
从基因表达综合数据库（GEO）（GEO109178）中下载 17 例 DMD 患者、11 例 BMD 患者和 6 例健康个体的股外侧肌活检样本的基因表达谱。通过 GEO2R 获得差异表达基因（DEGs）后，使用 R 包进行 WGCNA，筛选与 DMD、BMD 及其年龄或病理学高度相关的模块和基因。还进行了基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析和蛋白质-蛋白质相互作用（PPI）网络分析。使用 Search Tool for the Retrieval of Interacting Genes（STRING）和 Cytoscape 软件识别枢纽基因和高度相关聚类基因。
结果
在 DMD 与对照组之间鉴定出 1470 个 DEGs，其中 1281 个上调，189 个下调。在 BMD 与对照组之间发现 420 个 DEGs，其中 157 个上调，263 个下调。鉴定出 14 个不同颜色的 DMD 与对照组的模块，鉴定出 7 个不同颜色的 BMD 与对照组的模块。分别总结了 DMD 和 BMD 的 10 个枢纽基因，总结了 BMD 年龄的 5 个枢纽基因，总结了 DMD 年龄和 BMD 病理学的 5 和 3 个高度相关聚类基因。此外，发现 20 个 GO 富集参与 DMD，3 个 GO 富集参与 BMD，3 个 GO 富集参与 BMD 年龄。
结论
在 DMD 中，鉴定出几个枢纽基因：C3AR1、TLR7、IRF8、FYB 和 CD33（免疫和炎症相关基因）、TYROBP、PLEK、AIF1（肌动蛋白重排相关基因）、LAPTM5 和 NT5E（细胞死亡和动脉钙化相关基因）。在 BMD 中，鉴定出一些枢纽基因：LOX、ELN、PLEK、IKZF1、CTSK、THBS2、ADAMTS2、COL5A1（细胞外基质相关基因）、BCL2L1 和 CDK2（细胞周期相关基因）。
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