基于GEO数据库探讨阿尔茨海默病和骨质疏松的共病机制及潜在中药预测

Discussion on Comorbidity Mechanism of Alzheimer's Disease and Osteoporosis and Prediction of Potential Chinese Medicine based on GEO Database

目的:利用生物信息学方法,获取阿尔茨海默病(Alzheimer Disease,AD)与骨质疏松症(osteoporosis,OP)的差异基因和相关通路,并对其进行预测。方法:通过GEO数据库中的基因芯片数据,以AD-OP为研究对象,筛选出AD-OP患者的差异基因、蛋白相互作用网络,采用CytoHubba插件鉴定Hub基因,MCODE插件对与AD-OP发病密切相关的功能模块进行聚类分析,利用TRRUST数据库预测共同差异表达基因的转录因子。通过GO功能及KEGG通路,明确其作用机制,并利用验证组中的差异表达基因来验证上述研究结果。最后利用Coremine Medical数据库预测对关键基因具有显著调控作用的中药。结果:从GEO数据库获得AD-OP差异表达基因31个,导入STRING数据库进行检索得到27个节点和54条边组。MCODE插件聚类分析并挖掘2个疾病相关功能模块,CytoHubba插件在关联网络数据中查找25个hub基因并将其上传到GeneMANIA数据库中,得出ACTR1A、DCTN1、ARPC1B、CTTN等与核心基因最密切的基因,再用GO注释及KEGG通路分析上述基因。富集分析结果得出,多种神经退行性疾病的通路和p53信号通路等通路对AD-OP的发病至关重要。经TRRUST分析获得TP53、RELA、NFKB1以上3个主要的转录因子,还有MGP、CARM1、BCL2L1、BCL2、AXIN2、ACACA、UBE2C、PTP4A1、PTEN受转录因子调控的基因。采用COREMINE预测关键基因和通路,结果显示紫草、郁金、姜黄和黄精是治疗AD-OP的核心中药。结论:本研究明确了AD-OP的核心基因及基因所富集的通路,探讨了AD-OP主要涉及的生物学过程,并采用验证数据集验证了Hub基因,为AD-OP治疗的新靶点选择提供了支撑,预测了针对核心基因的治疗中药,为治疗AD-OP的治疗和研究提供了依据。

Objective:Use bioinformatics methods to obtain the differential genes and related pathways between Alzheimer Disease(AD)and osteoporosis(OP),and predict them.Methods:Through the gene chip data in the GEO database,taking AD-OP as the research object,the differential genes and protein interaction networks of AD-OP patients were screened out,and the CytoHubba plug-in was used to identify Hub genes.The MCODE plug-in pair was closely related to the onset of AD-OP.Cluster analysis was performed on related functional modules,and the TRRUST database was used to predict transcription factors of common differentially expressed genes.Through GO function and KEGG pathway,its mechanism of action was clarified,and the differentially expressed genes in the validation group were used to verify the above research results.Finally,the Coremine Medical database was used to predict traditional Chinese medicines that have significant regulatory effects on key genes.Results:31 AD-OP differentially expressed genes were obtained from the GEO database,and imported into the STRING database for retrieval,27 nodes and 54 edge groups were obtained.The MCODE plug-in performs cluster analysis and mines 2 disease-related functional modules.The CytoHubba plug-in finds 25 hub genes in the associated network data and uploads them to the GeneMANIA database.It is concluded that ACTR1A,DCTN1,ARPC1B,CTTN,etc.are most closely related to the core genes.genes,and then use GO annotation and KEGG pathways to analyze the above genes.The enrichment analysis results showed that pathways of multiple neurodegenerative diseases and the p53 signaling pathway are crucial to the pathogenesis of AD-OP.Through TRRUST analysis,three major transcription factors including TP53,RELA,and NFKB1 were obtained,as well as genes regulated by transcription factors such as MGP,CARM1,BCL2L1,BCL2,AXIN2,ACACA,UBE2C,PTP4A1,and PTEN.COREMINE was used to predict key genes and pathways,and the results showed that comfrey,turmeric,turmeric,and polygonatum are core Chinese medicines in the treatment of AD-OP.Conclusion:This study clarified the core genes of AD-OP and the gene-enriched pathways,explored the biological processes mainly involved in AD-OP,and used the validation data set to verify the Hub gene as a new target for AD-OP treatment.Point selection provides support and predicts therapeutic Chinese medicines targeting core genes,providing a basis for treatment and research on AD-OP.