融合分子与生物网络信息,提升药物相互作用预测的准确性与可解释性。
Towards Interpretable Drug-Drug Interaction Prediction: A Graph-Based Approach with Molecular and Network-Level Explanations
- 将药物对视为整体,结合分子结构与生物网络构建多尺度图模型。
- 在DrugBank数据集上达到AUC 0.921,优于现有方法。
- 支持从分子到网络层级的可解释分析,适合药理研究与安全评估。
药物-药物相互作用(DDIs)是药理学中的关键挑战,常导致严重不良反应,影响患者安全与医疗结果。尽管基于图的方法已取得良好预测性能,但多数方法将药物对独立处理,忽视了药物对间复杂且依赖上下文的相互作用特性,同时难以整合生物相互作用网络与分子结构以提供机制性洞察。本文提出MolecBioNet,一种新型图基框架,通过整合分子与生物医学知识,实现鲁棒且可解释的DDI预测。该框架将药物对建模为统一实体,捕捉宏观生物相互作用与微观分子影响,形成综合视角。具体地,从生物医学知识图谱中提取局部子图,并基于分子表示构建分层交互图,利用经典图神经网络学习药物对的多尺度表示。为提升准确率与可解释性,引入两种领域特定池化策略:上下文感知子图池化(CASPool),突出生物学相关实体;注意力引导影响池化(AGIPool),聚焦关键分子结构。此外,采用互信息最小化正则化增强嵌入融合中的信息多样性。实验表明,MolecBioNet在多个基准数据集上优于现有先进方法,消融实验与嵌入可视化进一步验证了统一药物对建模与多尺度知识融合的优势。
原文摘要 · Abstract (English)
Drug-drug interactions (DDIs) represent a critical challenge in pharmacology, often leading to adverse drug reactions with significant implications for patient safety and healthcare outcomes. While graph-based methods have achieved strong predictive performance, most approaches treat drug pairs independently, overlooking the complex, context-dependent interactions unique to drug pairs. Additionally, these models struggle to integrate biological interaction networks and molecular-level structures to provide meaningful mechanistic insights. In this study, we propose MolecBioNet, a novel graph-based framework that integrates molecular and biomedical knowledge for robust and interpretable DDI prediction. By modeling drug pairs as unified entities, MolecBioNet captures both macro-level biological interactions and micro-level molecular influences, offering a comprehensive perspective on DDIs. The framework extracts local subgraphs from biomedical knowledge graphs and constructs hierarchical interaction graphs from molecular representations, leveraging classical graph neural network methods to learn multi-scale representations of drug pairs. To enhance accuracy and interpretability, MolecBioNet introduces two domain-specific pooling strategies: context-aware subgraph pooling (CASPool), which emphasizes biologically relevant entities, and attention-guided influence pooling (AGIPool), which prioritizes influential molecular substructures. The framework further employs mutual information minimization regularization to enhance information diversity during embedding fusion. Experimental results demonstrate that MolecBioNet outperforms state-of-the-art methods in DDI prediction, while ablation studies and embedding visualizations further validate the advantages of unified drug pair modeling and multi-scale knowledge integration.
Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。