基于生物信息学分析识别老年骨质疏松症核心致病基因及通路

Identification of core pathogenic genes and pathways in elderly osteoporosis based on bioinformatics analysis

目的:采用生物信息学方法分析老年骨质疏松症相关的核心致病基因及相关通路。方法:于2020年11月至2021年8月,以在北京积水潭医院就诊的8例骨质疏松症病例和5名健康体检者为研究对象。采集8例老年骨质疏松症患者与5名健康体检者的外周血,开展高通量转录组测序,并对表达谱进行分析。对差异表达基因进行GO富集分析和KEGG通路富集分析。通过STRING、Cytoscape工具构建PPI调控网络、筛选核心基因。结果:8例骨质疏松症病例中,男性1例,女性7例,年龄为(72.4±4.2)岁;5名健康体检者中,男性1名,女性4名,年龄为(68.2±5.7)岁。分析筛选出差异表达基因1635个,其中847个基因高表达,788个基因低表达。GO富集分析结果显示,差异基因在分子功能方面主要富集于核糖体结构成分、蛋白质二聚化活性等;细胞组分方面主要富集于核小体、DNA组装复合物、胞质部分、蛋白-核酸复合物、游离核糖体等。KEGG信号通路分析结果显示,差异表达基因主要富集于系统性红斑狼疮、核糖体等。筛选出的10个核心基因分别为UBA52、UBB、RPS27 A、RPS15、RPS12、RPL13 A、RPL23 A、RPL10 A、RPS25和RPS6,且其中7个基因均可编码核糖体蛋白。结论:老年骨质疏松症的发病可能与核糖体相关基因和通路有关联。

Objective Using bioinformatics methods to analyze the core pathogenic genes and related pathways in elderly osteoporosis.Methods From November 2020 and August 2021,eight elderly osteoporosis patients who received treatment and five healthy participants who underwent physical examinations in Beijing Jishuitan Hospital were selected as subjects.The expression level of RNA in the peripheral blood of eight elderly osteoporosis patients and five healthy participants was collected for high-throughput transcriptome sequencing and analysis.The gene ontology(GO)analysis Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed for the differentially expressed genes(DEGs).The protein-protein interaction(PPI)network was constructed using the STRING website and Cytoscape software,and the most significant modules and hub genes were screened out.Results Among the eight elderly osteoporosis patients,there were seven females and one male,with an average age of 72.4 years(SD=4.2).Among the five healthy participants,there were four females and one male,with an average age of 68.2 years(SD=5.7).A total of 1635 DEGs(847 up-regulated and 788 down-regulated)were identified.GO analysis revealed that the molecular functions of DEGs were mainly enriched in structural constituents of the ribosome,protein dimerization activity,and cellular components were mainly enriched in the nucleosome,DNA packaging complex,cytosolic part,protein-DNA complex and the cytosolic ribosome.KEGG pathway analysis showed that DEGs were mainly enriched in systemic lupus erythematosus and ribosome.Gene UBA52,UBB,RPS27A,RPS15,RPS12,RPL13A,RPL23A,RPL10A,RPS25 and RPS6 were selected and seven of them could encode ribosome proteins.Conclusion The pathogenesis of elderly osteoporosis may be associated with ribosome-related genes and pathways.