随机森林算法预测绝经后骨质疏松症与2型糖尿病关联microRNA及其 靶向基因调控作用
Random forest algorithm predicts postmenopausal osteoporosis and type 2 diabetes associated microRNAs and their targeted gene regulation
  
DOI:10.3969/j.issn.1006-7108.2022.02.017
中文关键词:  绝经后骨质疏松症  2型糖尿病  随机森林  微小核糖核苷酸  生物信息学
英文关键词:postmenopausal osteoporosis  type 2 diabetes mellitus  random forest  microRNA  bioinformatics
基金项目:国家自然科学基金(81774378);广东省中医药局科研项目(20181203);广州市蔡迎峰名中医传承工作室建设项目(穗卫中医[2019]1号)
作者单位
潘俊曦 田天照 刘保新 张胜 冯庆辉 彭志华 蔡迎峰* 广州医科大学附属中医医院骨伤科广东 广州 510000 
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中文摘要:
      目的 借助随机森林算法筛选绝经后骨质疏松症与2型糖尿病关联microRNA,通过生物信息学分析其调控作用。方法 从GEO数据库获取绝经后骨质疏松症与2型糖尿病患者基因芯片数据,使用随机森林算法筛选与两疾病关联性较高的miRNA,通过表达量差异分析、ROC验证筛选出关键miRNA;通过Targetscan、miRWalk2.0和DIANA TOOLS等数据库预测靶向基因,构建关键miRNA-靶向基因调控网络,使用DAVID6.8进行GO、KEGG富集分析。结果 从GEO数据库获取GSE70318芯片数据,随机森林算法筛选重要性排名前10位的miRNA进行表达量差异分析,其中4个miRNA表达量显著差异,ROC验证后获得关键miRNA为hsa-miR-369-3p。数据库预测获得hsa-miR-369-3p的44个靶向基因,主要富集于细胞外基质组织、细胞锌离子稳态、染色质结合、矿物质吸收、代谢途径等GO过程及KEGG信号通路。结论 通过挖掘基因芯片数据,借助随机森林算法筛选出关联绝经后骨质疏松症与2型糖尿病的关键miRNA——hsa-miR-369-3p。hsa-miR-369-3p可能通过调控靶向基因所参与的生物学过程、分子信号通路,介导骨代谢与内分泌代谢活动,发挥关联调控绝经后骨质疏松症与2型糖尿病的作用。
英文摘要:
      Objective To screen the postmenopausal osteoporosis and type 2 diabetes mellitus-related microRNAs by using random forest algorithm, and to analyze their regulatory function with bioinformatics. Methods The expression profiling data was collected from Gene Expression Omnibus database. The two diseases-related microRNAs were screened using random forest algorithm. The key microRNAs were selected from above related microRNAs via differential expression analysis and ROC validation. Targetscan, miRWalk2.0, and DIANA TOOLS databases were used to predict targets for key microRNAs. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the target genes were performed using DAVID6.8 database. Results Top 10 microRNAs in GSE70318 chips from GEO bank were identified with random forest algorithm. Among those, the expression of 4 microRNAs was significantly different. The key microRNA hsa-miR-369-3p was obtained after ROC validation. Forty-four target genes of the key microRNA were predicted. The main enrichment of target genes was in extracellular matrix tissue, cell zinc ion homeostasis, chromatin binding, mineral absorption, metabolic pathways, and GO and KEGG signal pathways. Conclusion The key microRNA hsa-miR-369-3p, which is highly correlated with both postmenopausal osteoporosis and type 2 diabetes mellitus, is found out via random forest algorithm. This microRNA may play an important role in regulating these two diseases by the regulation of targeted genes involving biological process, molecular signal pathways, and by mediation of bone metabolism and endocrine metabolism.
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