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基于二硫化物化相关基因的慢性阻塞性肺疾病机器学习模型及免疫浸润识别

A machine learning model and identification of immune infiltration for chronic obstructive pulmonary disease based on disulfidptosis-related genes.

作者信息

Li Sijun, Zhu Qingdong, Huang Aichun, Lan Yanqun, Wei Xiaoying, He Huawei, Meng Xiayan, Li Weiwen, Lin Yanrong, Yang Shixiong

机构信息

Infectious Disease Laboratory, The Fourth People's Hospital of Nanning, Nanning, China.

Department of Tuberculosis, The Fourth People's Hospital of Nanning, Nanning, China.

出版信息

BMC Med Genomics. 2025 Jan 8;18(1):7. doi: 10.1186/s12920-024-02076-2.

Abstract

BACKGROUND

Chronic obstructive pulmonary disease (COPD) is a chronic and progressive lung disease. Disulfidptosis-related genes (DRGs) may be involved in the pathogenesis of COPD. From the perspective of predictive, preventive, and personalized medicine (PPPM), clarifying the role of disulfidptosis in the development of COPD could provide a opportunity for primary prediction, targeted prevention, and personalized treatment of the disease.

METHODS

We analyzed the expression profiles of DRGs and immune cell infiltration in COPD patients by using the GSE38974 dataset. According to the DRGs, molecular clusters and related immune cell infiltration levels were explored in individuals with COPD. Next, co-expression modules and cluster-specific differentially expressed genes were identified by the Weighted Gene Co-expression Network Analysis (WGCNA). Comparing the performance of the random forest (RF), support vector machine (SVM), generalized linear model (GLM), and eXtreme Gradient Boosting (XGB), we constructed the ptimal machine learning model.

RESULTS

DE-DRGs, differential immune cells and two clusters were identified. Notable difference in DRGs, immune cell populations, biological processes, and pathway behaviors were noted among the two clusters. Besides, significant differences in DRGs, immune cells, biological functions, and pathway activities were observed between the two clusters.A nomogram was created to aid in the practical application of clinical procedures. The SVM model achieved the best results in differentiating COPD patients across various clusters. Following that, we identified the top five genes as predictor genes via SVM model. These five genes related to the model were strongly linked to traits of the individuals with COPD.

CONCLUSION

Our study demonstrated the relationship between disulfidptosis and COPD and established an optimal machine-learning model to evaluate the subtypes and traits of COPD. DRGs serve as a target for future predictive diagnostics, targeted prevention, and individualized therapy in COPD, facilitating the transition from reactive medical services to PPPM in the management of the disease.

摘要

背景

慢性阻塞性肺疾病(COPD)是一种慢性进行性肺部疾病。二硫化物诱导细胞程序性坏死相关基因(DRGs)可能参与COPD的发病机制。从预测、预防和个性化医学(PPPM)的角度来看,阐明二硫化物诱导细胞程序性坏死在COPD发生发展中的作用可为该疾病的早期预测、靶向预防和个性化治疗提供契机。

方法

我们使用GSE38974数据集分析了COPD患者中DRGs的表达谱和免疫细胞浸润情况。根据DRGs,探讨了COPD患者的分子聚类和相关免疫细胞浸润水平。接下来,通过加权基因共表达网络分析(WGCNA)确定共表达模块和聚类特异性差异表达基因。比较随机森林(RF)、支持向量机(SVM)、广义线性模型(GLM)和极端梯度提升(XGB)的性能,构建最佳机器学习模型。

结果

鉴定出差异表达的DRGs、差异免疫细胞和两个聚类。在两个聚类之间,DRGs、免疫细胞群体、生物学过程和信号通路行为存在显著差异。此外,两个聚类之间在DRGs、免疫细胞、生物学功能和信号通路活性方面也观察到显著差异。创建了列线图以辅助临床程序的实际应用。SVM模型在区分不同聚类的COPD患者方面取得了最佳结果。随后,我们通过SVM模型确定了前五个基因作为预测基因。与该模型相关的这五个基因与COPD患者的特征密切相关。

结论

我们的研究证明了二硫化物诱导细胞程序性坏死与COPD之间的关系,并建立了一个最佳机器学习模型来评估COPD的亚型和特征。DRGs可作为未来COPD预测诊断、靶向预防和个体化治疗的靶点,有助于在该疾病的管理中从被动医疗服务向PPPM转变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44d7/11715737/ff237bc1571a/12920_2024_2076_Fig1_HTML.jpg

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