EGWO-GAT:一种用于膀胱尿路上皮癌分期诊断的图注意力网络与增强型灰狼优化算法多组学整合模型OA
EGWO-GAT:A graph attention network and enhanced grey wolf optimizer-based multi-omics integration model for bladder urothelial carcinoma staging diagnosis
目的 本研究提出了一种基于图注意力网络(graph attention network,GAT)与增强型灰狼优化算法(enhanced-grey wolf optimizer,EGWO)的多组学整合模型EGWO-GAT,实现对膀胱尿路上皮癌(bladder urothelial carcinoma,BLCA)肿瘤样本的分期预测.方法 基于在加州大学圣克鲁斯分校Xena功能基因组学探索器(University of California,Santa Cruz Xena,UCSC Xena)网站收集的404例癌症基因组图谱(The Cancer Genome Atlas,TCGA)BLCA样本,包含mRNA、DNA甲基化和微小RNA(microRNA,miRNA)数据,将3种组学数据分别进行预处理和差异分析之后得到其节点特征与边特征,以GAT为基础,引入EGWO进行超参数优化,采用多层感知机(multilayer perceptron,MLP)进行后续癌症分期预测.经5折交叉验证分析,将本研究创建的EGWO-GAT模型与多种经典机器学习分期模型的性能进行对比,并进行组学贡献分析和保留不同相似边条数的模型性能比较,采用准确率、精确率、召回率、F1分数及曲线下面积(area under the curve,AUC)作为性能评估的核心指标.结果 差异特征筛选结果显示,mRNA组学获得534个差异基因,DNA甲基化组学获得3 108个差异探针,miRNA组学获得114个差异miRNA.多模型对比结果表明,当整合所有组学数据类型且保留相似性排名前3的其他患者作为边时,EGWO-GAT模型性能最佳,其AUC值达到0.744,准确率达到0.711,精确率达到0.792,召回率达到0.782,F1分数达到0.785,其综合分类性能显著优于其余经典机器学习方法,且较GS-GAT模型在各项指标上均有明显提升.组学贡献分析显示,全组学(mRNA+DNA甲基化+miRNA)整合的性能显著优于其他6种组学组合方式.相似性边数性能比较结果表明,保留前3条相似边时模型的AUC、准确率、精确率及F1分数均高于保留前5条或7条边的情况,综合性能最优.结论 本研究构建的EGWO-GAT多组学整合模型在BLCA分期中性能优异,可为精准分期提供技术支撑,解决因样本异质性引发的临床分期难题,对辅助个体化治疗及改善患者预后意义重大.
Objective This study proposes a multi-omics integration model,EGWO-GAT,based on graph attention network(GAT)and enhanced-grey wolf optimizer(EGWO),for staging prediction of bladder urothelial carcinoma(BLCA)samples.Methods A total of 404 BLCA samples from The Cancer Genome Atlas(TCGA)were collected from the University of California,Santa Cruz Xena(UCSC Xena)functional genomics explorer,including mRNA,DNA methylation,and microRNA(miRNA)data.After separate preprocessing and differential analysis of the 3 omics datasets,node features and edge features were extracted.Using GAT as the backbone framework,EGWO was employed for hyperparameter optimization,and multilayer perceptron(MLP)was applied for cancer staging prediction.Through 5-fold cross-validation,the performance of EGWO-GAT was compared with classical machine learning models,along with omics contribution analysis and performance conparison of models retaining different numbers of similar edges.Accuracy,precision,recall,F1 score,and area under the curve(AUC)were used as core evaluation metrics.Results Differential feature screening identified 534 differentially expressed genes in mRNA,3 108 differential probes in DNA methylation,and 114 differential miRNAs.Model comparisons showed that EGWO-GAT achieved optimal performance when integrating all omics data and retaining edges from the top 3 similar patients,with an AUC value of 0.744,an accuracy of 0.711,a precision of 0.792,a recall of 0.782,and an F1 score of 0.785.Its performance significantly surpassed other classical methods and outperformed the GS-GAT model across all metrics.Omics contribution analysis confirmed that full integration(mRNA+DNA methylation+miRNA)outperformed all other combinations.Result of the similarity edge number performance comparison demonstrated that retaining the top 3 similar edges yielded the highest AUC,accuracy,precision,and F1 score compared to the top 5 or 7 edges.Conclusion The EGWO-GAT model exhibits excellent performance in BLCA staging,providing reliable technical support for precise diagnosis.It addresses clinical challenges caused by sample heterogeneity and holds significant potential for guiding individualized treatment and improving patient prognosis.
郭泓麟;秦茂洋;宋秋月;陈欣;伍亚舟
陆军军医大学(第三军医大学)军事预防医学系军队卫生统计学教研室,重庆陆军军医大学(第三军医大学)军事预防医学系军队卫生统计学教研室,重庆陆军军医大学(第三军医大学)军事预防医学系军队卫生统计学教研室,重庆陆军军医大学(第三军医大学)军事预防医学系军队卫生统计学教研室,重庆陆军军医大学(第三军医大学)军事预防医学系军队卫生统计学教研室,重庆
医药卫生
膀胱尿路上皮癌图注意力网络增强型灰狼优化算法多组学
bladder urothelial carcinomagraph attention networkenhanced-grey wolf optimizermulti-omics
《陆军军医大学学报》 2026 (3)
366-377,12
国家自然科学基金面上项目(82173621,82574207) Supported by the General Program of the National Natural Science Foundation of China(82173621,82574207).
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