摘要
目的基于机器学习筛选和验证严重创伤早期的细胞程序性死亡(PCD)核心基因,并探讨其生物学机制。方法通过GEO数据库检索符合条件的严重创伤早期(创伤发生后12 h内)基因芯片,对其进行标准化处理,并将其分成训练集和测试集,将训练集作为后续实验的数据集,通过差异分析获得19种PCD相关差异基因。利用蛋白质互作网络分析获取了网络关键基因,随后采用随机森林、最小绝对收缩和选择算子、极端梯度提升、梯度提升机、弹性网络从这些基因中进一步筛选,取交集获得核心基因。绘制训练集和测试集受试者工作特征(ROC)曲线加以验证。结果训练集中共得到416个差异表达程序性死亡基因,通过蛋白互作分析进一步获得10个网络关键基因。使用机器学习算法筛选出4个核心基因STAT3、IL-10、HDAC1、PIK3R1,在训练集和测试集绘制ROC曲线的AUC值均>0.9且差异表达一致。结论阶段性地采用机器学习方法筛选出严重创伤早期与程序性死亡相关的核心基因,探讨了这些基因通过调控细胞程序性死亡途径影响免疫稳态重塑与炎症反应,进而驱动创伤病理进程的潜在机制,但其具体分子机制有待后续实验验证。
Objective To identify and validate core genes related to programmed cell death(PCD)for early severe trauma(≤12 h post-injury)and to explore their biological significance.Methods Gene expression datasets from the GEO database were standardized and split into training/testing sets.Differential analysis identified 19 PCD-related genes.Protein-protein interaction network analysis revealed hub genes,further refined by five machine learning algorithms(random forest,least absolute shrinkage and selection operator,XGBoost,gradient boosting machine,elastic net).Core genes were validated via ROC curves and neural networks.Results From the 416 PCD-related differential expressed genes,10 hub genes emerged.Four core genes(STAT3,IL-10,HDAC1,PIK3R1)showed consistent differentially expression and high predictive accuracy(AUC>0.9)across the datasets.Conclusion A stepwise machine learning approach was employed to identify core PCD-related genes in the early stages of severe trauma.This study investigated the potential mechanisms by which these genes modulate immune homeostasis remodeling and inflammatory responses through regulatory pathways of programmed cell death,thereby contributing to trauma-induced pathological progression.However,the specific molecular interactions underlying these observations warrant further experimental validation.
作者
姚乐
刘志兵
韩振远
陆冠宇
王鑫
Yao Le;Liu Zhibing;Han Zhenyuan;Lu Guanyu;Wang Xin(Department of Emergency,Beihai People’s Hospital,Beihai,Guangxi Province 536000,China;Grade 2021 of School of Medical Imaging,North Sichuan Medical College,Nanchong,Sichuan Province 637000,China)
出处
《创伤外科杂志》
2025年第5期389-393,共5页
Journal of Traumatic Surgery
