GWGS芯片整合分析识别外周血细胞中与骨质疏松症相关的枢纽基因

Identification of Osteoporosis Related Hub Genes in Peripheral Blood Cells by Integration Analysis of Microarray Data Using GWGS Method

为了对骨质疏松症基因芯片数据集进行整合分析并识别出外周血细胞中与骨质疏松症相关的枢纽基因,通过检索GEO和ArrayExpress数据库获得骨质疏松症相关的表达谱芯片数据集;运用GWGS(genome-wide global significance)方法对纳入的数据集进行整合分析,筛选出差异表达基因(differentially expressed genes,DEGs);然后,运用GO(gene ontology)富集分析和KEGG(kyoto encyclopedia of genes and genomes)通路富集分析对差异表达基因进行功能注释,并建立蛋白质相互作用(protein-protein interaction,PPI)网络,筛选出骨质疏松症相关的枢纽基因。公共数据库检索得到3个符合纳入排除标准的研究集,GWGS整合分析筛选出排序前200的DEGs,这些基因主要富集的GO条目为脂多糖的细胞反应、凋亡过程和炎症反应,与骨质疏松症相关的KEGG富集通路为破骨细胞分化等。PPI分析进一步检测到与骨质疏松症相关的10个枢纽基因,其中9个基因已有研究报道和骨质疏松症的发生发展相关,而ELANE基因还未有研究报道与骨质疏松症有关。ELANE基因同时在人的骨髓组织、小鼠骨髓和骨组织中高表达,这个基因很可能与骨质疏松症有潜在的联系。本研究的结果将有助于进一步理解骨质疏松症的分子致病机理。

To identify hub genes of osteoporosis by integration analysis using microarray data,the osteoporosis-related gene expression data were collected from public databases,i.e.GEO and ArrayExpress,and then the genome-wide global significance(GWGS)method was applied to integrate the identified data and screen the differentially expressed genes(DEGs).GO and KEGG pathway analysis of the DEGs were used for the functional annotation.Protein-protein interaction(PPI)network was constructed to find the hub genes.Three datasets that met the inclusion and exclusion criteria were included in the analysis.The top 200 DEGs were selected according to the GWGS values.These genes were mainly enriched in three GO terms,including cellular response to lipopolysaccharide,apoptotic process,and inflammatory response.Osteoporosis related signaling pathway,i.e.osteoclast differentiation,was enriched in KEGG pathway analysis.The PPI networkanalys is identified 10 hub genes of osteoporosis.Nine of them have been reported to be related to the development of osteoporosis,while the gene ELANE has not been reported to be related to osteoporosis.ELANE was found to have high expression in human bone marrow,mouse bone marrow and bone.This indicates that it could be involved in the pathogenesis of osteoporosis.Results from this study may be helpful for further understanding the molecular pathogenesis of osteoporosis.