机器学习法筛选膝骨关节炎凋亡生物标志物及免疫浸润分析
Screening apoptosis-related genes and analyzing immune infiltration in knee osteoarthritis based on machine learning
  
DOI:10.3969/j.issn.1006-7108.2025.01.004
中文关键词:  膝骨关节炎  凋亡相关基因  机器学习  免疫浸润  WGCNA  lasso算法
英文关键词:knee osteoarthritis  apoptosis-related genes  machine learning  immune infiltration  WGCNA  Lasso algorithm
基金项目:内蒙古自治区科技计划项目(2022YFSH0075);内蒙古自治区研究生科研创新项目(S20231189Z);内蒙古自治区直属高校基本科研业务费项目(YKD2023ZY001);内蒙古自治区卫生健康委公立医院高水平临床专科发展科技项目(2023SGGZ143);内蒙古医科大学面上项目(YKD2022MS036)
作者单位
赵连兴1# 杜欣瑞1# 马超1 刘凯2 孟令婷2 王杏如2 左媛1* 王建忠1* 1.内蒙古医科大学第二附属医院内蒙古 呼和浩特 010000 2.内蒙古医科大学内蒙古 呼和浩特 010000 
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中文摘要:
      目的 利用机器学习算法筛选膝骨关节炎中差异性凋亡相关基因(differential apoptosis-related genes,DARGs),以进一步鉴定相关生物标志物,阐释凋亡在膝骨关节炎发病机制中的作用。方法 首先,通过GEO数据库下载并整合数据集GSE55235和GSE169077的基因表达矩阵,利用R包对整合的基因表达矩阵分别进行差异分析和WGCNA分析。而后将两种分析结果与genecards数据库中获取的凋亡相关基因取交集得到DARGs,对其进行GO、KEGG和GSEA富集分析。最后,通过cytoscape中的MCODE插件筛选DARGs蛋白质间相互作用关系最紧密的模块,运用lasso算法筛选出其中hub基因生物标志物,并在骨关节炎数据集GSE178557中绘制ROC曲线进行验证,对验证效果较好的hub基因生物标志物进行构建Gene-miRNA-转录因子-药物调控网络以及免疫浸润分析。结果 经筛选共得到189个DARGs,经验证集验证最终得到7个可靠的hub基因生物标志物,并预测了这些基因的miRNA的调控网络和转录因子调控网络,并获得了对hub基因生物标志物有潜在作用的药物和免疫细胞浸润分析结果。结论 凋亡在膝骨关节炎发病机制中具有重要作用,7个hub基因生物标志物包括TYROBP、COL14A1、CD74、LAMA4、COL5A1、MMP13、IGFBP5为诊断以及深入了解膝骨关节炎机制提供有价值的线索。
英文摘要:
      Objective To use machine learning algorithms to screen differentially apoptotic related genes (DARGs) in knee osteoarthritis, in order to further identify relevant biomarkers and to elucidate the role of apoptosis in the pathogenesis of knee osteoarthritis. Methods Firstly, the gene expression matrices of datasets GSE55235 and GSE169077 were downloaded and integrated from the GEO database. The differential analysis and WGCNA analysis on the integrated gene expression matrices were performed using R packages, respectively. Then, the two analysis results were intersected with apoptosis related genes obtained from the Genecards database to obtain DARGs, which were subjected to GO, KEGG, and GSEA enrichment analysis. Finally, the MCODE plugin in Cytoscape was used to screen the modules with the closest protein-protein interactions among DARGs. The Lasso algorithm was used to screen the hub gene biomarkers, and ROC curves were drawn in the osteoarthritis dataset GSE178557 for validation. The gene miRNA transcription factor drug regulatory network and immune infiltration analysis were performed on the hub gene biomarkers with good validation results. Results After screening, a total of 189 DARGs were obtained. After validation with a validation set, 7 reliable hub gene biomarkers were ultimately obtained. The miRNA regulatory network and transcription factor regulatory network of these genes were predicted. The potential drug and immune cell infiltration analysis results for hub gene biomarkers were obtained. Conclusion Apoptosis plays an important role in the pathogenesis of knee osteoarthritis. Seven hub gene biomarkers including TYROBP, COL14A1, CD74, LAMA4, COL5A1, MMP13, and IGFBP5 provide valuable clues for diagnosis and in-depth understanding of the mechanism of knee osteoarthritis.
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