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
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陈刚,男,主治医师,主要研究方向是中医药防治骨关节炎。

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R 681

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河南省中医药科学研究专项课题(20–21ZY2239)


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

    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:

    AbstractObjective 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.

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  • 收稿日期:2023-11-21
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  • 在线发布日期: 2024-06-07
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