用生成模型合成多组学数据,提升阿尔茨海默病与癌症预测准确率。
Transforming Multi-Omics Integration with GANs: Applications in Alzheimer's and Cancer
- 基于GAN生成高质多组学数据,保留生物关联性
- 合成数据使分类AUC最高提升0.10,显著改善预测性能
- 适合精准医疗、生物标志物与药物重定位研究者
多组学数据整合对理解复杂疾病至关重要,但样本量小、噪声大和异质性常降低预测能力。为此,我们提出Omics-GAN,一种基于生成对抗网络(GAN)的框架,用于生成高质量合成多组学谱,同时保持生物学关系。在阿尔茨海默病(AD)的ROSMAP队列及结肠癌和肝癌的TCGA数据集上,评估了三种组学类型(mRNA、miRNA、DNA甲基化)。支持向量机(SVM)结合重复5折交叉验证显示,合成数据持续提升预测准确率:在AD中mRNA的AUC从0.72升至0.74;在肝癌中从0.68升至0.72;结肠癌的miRNA从0.59升至0.69;肝癌甲基化从0.64升至0.71。箱线图分析表明合成数据保留统计分布,减少噪声和异常值。特征选择识别出与原始数据重叠的显著基因,并发现经GO和KEGG富集验证的额外候选基因。分子对接揭示潜在药物重定位候选物,包括尼洛替尼(用于AD)、ATOVQUONE(用于肝癌)和特考维拉莫(用于结肠癌)。Omics-GAN增强疾病预测,保持生物保真度,加速生物标志物与药物发现,为精准医疗提供可扩展策略。
原文摘要 · Abstract (English)
Multi-omics data integration is crucial for understanding complex diseases, yet limited sample sizes, noise, and heterogeneity often reduce predictive power. To address these challenges, we introduce Omics-GAN, a Generative Adversarial Network (GAN)-based framework designed to generate high-quality synthetic multi-omics profiles while preserving biological relationships. We evaluated Omics-GAN on three omics types (mRNA, miRNA, and DNA methylation) using the ROSMAP cohort for Alzheimer's disease (AD) and TCGA datasets for colon and liver cancer. A support vector machine (SVM) classifier with repeated 5-fold cross-validation demonstrated that synthetic datasets consistently improved prediction accuracy compared to original omics profiles. The AUC of SVM for mRNA improved from 0.72 to 0.74 in AD, and from 0.68 to 0.72 in liver cancer. Synthetic miRNA enhanced classification in colon cancer from 0.59 to 0.69, while synthetic methylation data improved performance in liver cancer from 0.64 to 0.71. Boxplot analyses confirmed that synthetic data preserved statistical distributions while reducing noise and outliers. Feature selection identified significant genes overlapping with original datasets and revealed additional candidates validated by GO and KEGG enrichment analyses. Finally, molecular docking highlighted potential drug repurposing candidates, including Nilotinib for AD, Atovaquone for liver cancer, and Tecovirimat for colon cancer. Omics-GAN enhances disease prediction, preserves biological fidelity, and accelerates biomarker and drug discovery, offering a scalable strategy for precision medicine applications.
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