用树模型构建可解释的多组学图神经网络,提升疾病分类准确率与可读性。
MOTGNN: Interpretable Graph Neural Networks for Multi-Omics Disease Classification
- 基于XGBoost生成组学特异性图结构,自动建模数据关系
- 在三个真实数据集上准确率比现有方法高5-10%,抗类别不平衡
- 能识别关键生物标志物并揭示各组学贡献度,适合临床研究者
整合DNA甲基化、mRNA表达和微小RNA(miRNA)表达等多组学数据,有助于全面理解疾病生物学机制。然而,多组学数据维度高、模态异质性强,且缺乏可靠的生物相互作用网络,导致有效融合困难。现有模型常依赖人工设计的相似性图,易受类别不平衡影响,且缺乏内置可解释性,限制其在生物医学中的应用。本文提出多组学集成树生成图神经网络(MOTGNN),一种用于二分类疾病的新型可解释框架。MOTGNN利用极端梯度提升(XGBoost)进行组学特异性监督图构建,随后通过模态特异性图神经网络(GNNs)进行分层表征学习,并使用深层前馈网络实现跨组学融合。在三个真实疾病数据集上,MOTGNN在准确率、ROC-AUC和F1分数上均比现有最优基线提升5-10%,且对严重类别不平衡保持鲁棒性。模型通过稀疏图保持计算效率,并提供内置可解释性,揭示了关键生物标志物及各组学模态的相对贡献。结果表明,MOTGNN在提升多组学疾病建模预测精度与可解释性方面具有潜力。
原文摘要 · Abstract (English)
Integrating multi-omics data, such as DNA methylation, mRNA expression, and microRNA (miRNA) expression, offers a comprehensive view of the biological mechanisms underlying disease. However, the high dimensionality of multi-omics data, the heterogeneity across modalities, and the lack of reliable biological interaction networks make meaningful integration challenging. In addition, many existing models rely on handcrafted similarity graphs, are vulnerable to class imbalance, and often lack built-in interpretability, limiting their usefulness in biomedical applications. We propose Multi-Omics integration with Tree-generated Graph Neural Network (MOTGNN), a novel and interpretable framework for binary disease classification. MOTGNN employs eXtreme Gradient Boosting (XGBoost) for omics-specific supervised graph construction, followed by modality-specific Graph Neural Networks (GNNs) for hierarchical representation learning, and a deep feedforward network for cross-omics integration. Across three real-world disease datasets, MOTGNN outperforms state-of-the-art baselines by 5-10% in accuracy, ROC-AUC, and F1-score, and remains robust to severe class imbalance. The model maintains computational efficiency through the use of sparse graphs and provides built-in interpretability, revealing both top-ranked biomarkers and the relative contributions of each omics modality. These results highlight the potential of MOTGNN to improve both predictive accuracy and interpretability in multi-omics disease modeling.
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