基于CMap数据库分析骨质疏松症相关基因及潜在治疗药物

Analysis of genes and potential therapeutic drugs related toosteoporosis based on CMap Database

目的基于CMap数据库筛选骨质疏松症(OP)相关基因及潜在治疗药物,为OP的治疗提供新思路。方法检索GEO数据库中关于OP的相关芯片,采用R语言分析差异基因;检索疾病基因公共数据库,获得已知OP的相关致病基因,通过映射获得OP的致病关键靶点,构建作用靶点的蛋白质-蛋白质相互作用关系(PPI)网络,利用DAVID数据库对关键基因进行GO分析和KEGG通路分析,采用关联性图谱(CMap)数据库筛选出负相关的小分子化合物。结果检索GEO数据库筛选出GSE56116的芯片,利用R语言分析筛选出69个上调基因和106个下调基因;通过检索GAD、TTD、OMIM、DrugBank、PharmGKB和DisGeNET数据库,得到691个与OP发病相关的已知靶点,通过映射获得OP致病的14个关键基因;DAVID数据库富集分析结果显示,OP关键靶点主要与免疫反应、对过氧化氢的反应、抗原处理和呈递等生物学过程相关。借助CMap数据库结果显示,地高辛、橙皮苷等小分子化合物具有较高的负相关。结论借助生物信息学和CMap数据库挖掘,地高辛和橙皮苷等小分子化合物可能为OP的候选治疗药物。同时,本研究方法为发现疾病的候选治疗药物开辟了新途径和思路。

Objective To screen genes and potential therapeutic drugs related to osteoporosis(OP)based on CMap database,and to provide a new idea for the treatment of OP.Methods The chips related to OP in GEO database were searched and the differential genes were analyzed by R.The public databases of disease genes were searched.The related pathogenic genes of OP were obtained.The key targets of OP were obtained,and the network of protein-protein interaction(PPI)was constructed.The GO and KEGG pathway were analyzed by DAVID database,and the small molecular compounds of negative correlation were screened out by connectivity map(CMap)database.Results The chip of GSE56116 was screened out from GEO database,and 69 up-regulated genes and 106 down-regulated genes were screened by R.By searching GAD,TTD,OMIM,DrugBank,PharmGKB and DisGeNET databases,691 known targets related to the pathogenesis of OP were obtained,and 14 key genes of OP were obtained.The results of enrichment analysis by DAVID database showed that the key targets of OP were mainly related to immune response,reaction to hydrogen peroxide,antigen processing and presentation.The results of CMap database showed that digoxin,hesperidin and other small molecular compounds had high negative correlation.Conclusion With the application of bioinformatics and CMap database,it is found that small molecular compounds such as digoxin and hesperidin may be candidates for the treatment of OP.Besides,this research method provides a new way and train of thought for finding candidate therapeutic drugs for diseases.