深圳中西医结合杂志2024,Vol.34Issue(2) :4-10,后插1-后插2.DOI:10.16458/j.cnki.1007-0893.2024.02.002

基于生物信息学和机器学习筛选阴虚质绝经后骨质疏松症关键基因的研究

Screening of Key Genes for Oosteoporosis in Postmenopausal Osteoporosis with Yin Deficiency Based on Bioinformatics and Machine Learning

陈刚 李峰 郭珈宜 高泉阳 郭艳幸 郭艳锦
深圳中西医结合杂志2024,Vol.34Issue(2) :4-10,后插1-后插2.DOI:10.16458/j.cnki.1007-0893.2024.02.002

基于生物信息学和机器学习筛选阴虚质绝经后骨质疏松症关键基因的研究

Screening of Key Genes for Oosteoporosis in Postmenopausal Osteoporosis with Yin Deficiency Based on Bioinformatics and Machine Learning

陈刚 1李峰 1郭珈宜 1高泉阳 1郭艳幸 1郭艳锦1
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作者信息

  • 1. 洛阳正骨医院 河南省骨科医院,河南 洛阳 471002
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摘要

目的:应用生物信息学和机器学习的方法筛选阴虚质绝经后骨质疏松症(PMOP)中的关键基因.方法:从基因表达数据库(GEO)数据库下载GSE87474 中平和质和阴虚体质人群的外周血单核细胞数据,下载与PMOP相关的数据集GSE56116 和GSE100609,并用SVA包进行合并.其次,利用加权基因共表达网络分析筛选与中医阴虚质密切相关的基因;利用limma包筛选合并数据集中的差异表达基因;并将两者取交集获取与阴虚质PMOP相关的基因.然后,通过最小绝对值收敛和选择算子(LASSO)、支持向量机-递归特征消除(SVM-RFE)和随机森林(RF)算法,识别阴虚质PMOP过程中潜在的关键基因,并评价其诊断效能.最后,对关键基因开展单基因的基因集富集分析(GSEA).结果:共获得 46 个与阴虚质PMOP相关的基因,利用LASSO、SVM-RFE和RF算法从其中筛选出 1 个关键基因即溶质载体家族 39 成员 8(SLC39A8).单基因GSEA显示,SLC39A8 高表达组富集到了HIPPO、白细胞介素-12、P38MAPK、P53、细胞凋亡等 104 个信号通路.结论:本研究发现SLC39A8 可能为阴虚质PMOP的关键基因,结果可为进一步阐释阴虚质PMOP分子机制及从中医体质学说论治PMOP提供新的思路和切入点.

Abstract

Objective To apply bioinformatics and machine learning to screen for key genes in postmenopausal osteoporosis(PMOP)with Yin deficiency.Methods The peripheral blood mononuclear cell data of GSE87474 people with moderate constitution and yin deficiency constitution were downloaded from GEO database,and the data sets GSE56116 and GSE100609 related to PMOP were downloaded and combined with SVA package.Secondly,weighted gene co-expression network was used to screen genes closely related to Yin deficiency in traditional Chinese medicine(TCM).limma package was used to screen the differentially expressed genes in the combined data set.They were intersected to obtain genes associated with Yin deficiency PMOP.Then,the minimum absolute convergence and selection operator(LASSO),support vector machine-recursive feature elimination(SVM-RFE)and random forest(RF)algorithms were used to identify potential key genes in the process of PMOP in Yin deficiency and evaluate their diagnostic effectiveness.Finally,single gene set enrichment analysis(GSEA)was performed for key genes.Results A total of 46 genes related to PMOP with Yin-deficiency constitution were obtained,and one key gene,solute carrier family 39 member 8(SLC39A8),was screened out by using LASSO,SVM-RFE and RF algorithms.Single-gene GSEA showed that the SLC39A8 high expression group was enriched in 104 signaling pathways including HIPPO,interleukin-12,P38MAPK,P53,and apoptosis.Conclusion This study found that SLC39A8 may be the key gene of PMOP in Yin deficiency,and the results can provide a new idea and breakthrough point for further elucidation of the molecular mechanism of PMOP in Yin deficiency and the treatment of PMOP from the constitution theory of TCM.

关键词

绝经后骨质疏松症/阴虚质/生物信息学/机器学习/生物标志物

Key words

Postmenopausal osteoporosis/Constitution with Yin-deficiency/Bioinformatics/Machine learning/Biomarkers

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基金项目

河南省中医药科学研究专项(20-21ZY2239)

出版年

2024
深圳中西医结合杂志
深圳市中西医结合临床研究所

深圳中西医结合杂志

影响因子:0.692
ISSN:1007-0893
参考文献量49
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