用图神经网络预测药物协同效应,提升准确率与可解释性。
Drug Synergy Prediction via Residual Graph Isomorphism Networks and Attention Mechanisms

- 通过残差图同构网络捕捉分子多尺度拓扑特征
- 在五个公开数据集上优于主流模型,泛化能力更强
- 适合药物研发与精准医疗领域的研究人员使用
复杂疾病治疗中,单一药物疗效有限且易产生耐药性,而联合用药可通过协同作用显著改善疗效。然而,实验验证所有可能的药物组合成本过高,亟需高效的计算预测方法。尽管基于深度学习和图神经网络(GNN)的方法已有进展,仍存在结构偏差、泛化能力弱和可解释性差等问题。本文提出一种融合分子结构特征、细胞系基因组信息与药物-药物相互作用的协同预测图神经网络,命名为残差图同构网络结合注意力机制(ResGIN-Att)。该模型首先利用残差图同构网络提取药物分子的多尺度拓扑特征,残差连接缓解深层网络中的过平滑问题;随后,自适应长短期记忆(LSTM)模块从局部到全局融合结构信息;最后,交叉注意力模块显式建模药物间相互作用并识别关键化学子结构。在五个公开基准数据集上的实验表明,ResGIN-Att表现优异,相较于关键基线方法具有更强的泛化能力和鲁棒性。
原文摘要 · Abstract (English)
In the treatment of complex diseases, treatment regimens using a single drug often yield limited efficacy and can lead to drug resistance. In contrast, combination drug therapies can significantly improve therapeutic outcomes through synergistic effects. However, experimentally validating all possible drug combinations is prohibitively expensive, underscoring the critical need for efficient computational prediction methods. Although existing approaches based on deep learning and graph neural networks (GNNs) have made considerable progress, challenges remain in reducing structural bias, improving generalization capability, and enhancing model interpretability. To address these limitations, this paper proposes a collaborative prediction graph neural network that integrates molecular structural features and cell-line genomic profiles with drug-drug interactions to enhance the prediction of synergistic effects. We introduce a novel model named the Residual Graph Isomorphism Network integrated with an Attention mechanism (ResGIN-Att). The model first extracts multi scale topological features of drug molecules using a residual graph isomorphism network, where residual connections help mitigate over-smoothing in deep layers. Subsequently, an adaptive Long Short-Term Memory (LSTM) module fuses structural information from local to global scales. Finally, a cross-attention module is designed to explicitly model drug-drug interactions and identify key chemical substructures. Extensive experiments on five public benchmark datasets demonstrate that ResGIN-Att achieves competitive performance, comparing favorably against key baseline methods while exhibiting promising generalization capability and robustness.
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