arXiv:2505.19144cs.LGq-bio.QM2025-05

用双注意力与精度自适应量化,高效精准预测药物协同效应

DPASyn: Mechanism-Aware Drug Synergy Prediction via Dual Attention and Precision-Aware Quantization

  • 通过双注意力机制联合建模药物内部结构与跨药物互作
  • 在13243种组合上超越7个前沿模型,训练提速3倍且内存降40%
  • 适合需要高效高精度药物组合筛选的药企与研究团队

药物组合在癌症治疗中至关重要,利用药物-药物相互作用(DDI)提升疗效并对抗耐药性。然而,庞大的组合空间使实验筛选不切实际,现有计算模型难以捕捉DDI复杂的双向特性,常依赖独立编码或简单融合策略,忽略分子间精细动态。此外,主流图模型计算开销大,限制了真实药物发现中的可扩展性。为此,我们提出DPASyn框架,采用双注意力机制与精度自适应量化(PAQ)。双注意力通过共享投影和跨药物注意力,联合建模药物内结构与药物间互作,实现细粒度、生物合理的协同建模。尽管表达能力增强带来更高资源消耗,但PAQ通过动态优化训练中的数值精度,减少40%内存占用,加速训练三倍,且不牺牲准确率。结合层归一化稳定的残差连接,DPASyn在13,243种组合的O'Neil数据集上超越7个先进方法,并支持单张GPU全批量处理最多256个图,树立了高效与高表达力药物协同预测的新标准。

原文摘要 · Abstract (English)

Drug combinations are essential in cancer therapy, leveraging synergistic drug-drug interactions (DDI) to enhance efficacy and combat resistance. However, the vast combinatorial space makes experimental screening impractical, and existing computational models struggle to capture the complex, bidirectional nature of DDIs, often relying on independent drug encoding or simplistic fusion strategies that miss fine-grained inter-molecular dynamics. Moreover, state-of-the-art graph-based approaches suffer from high computational costs, limiting scalability for real-world drug discovery. To address this, we propose DPASyn, a novel drug synergy prediction framework featuring a dual-attention mechanism and Precision-Aware Quantization (PAQ). The dual-attention architecture jointly models intra-drug structures and inter-drug interactions via shared projections and cross-drug attention, enabling fine-grained, biologically plausible synergy modeling. While this enhanced expressiveness brings increased computational resource consumption, our proposed PAQ strategy complements it by dynamically optimizing numerical precision during training based on feature sensitivity-reducing memory usage by 40% and accelerating training threefold without sacrificing accuracy. With LayerNorm-stabilized residual connections for training stability, DPASyn outperforms seven state-of-the-art methods on the O'Neil dataset (13,243 combinations) and supports full-batch processing of up to 256 graphs on a single GPU, setting a new standard for efficient and expressive drug synergy prediction.

药物协同双注意力量化图神经网络

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