arXiv:2601.15771cs.LGq-bio.BM2026-01

将药物相互作用预测转为关系学习,提升对新药的泛化能力。

Rethinking Drug-Drug Interaction Modeling as Generalizable Relation Learning

  • 把药物相互作用建模为独立于具体药物的关系,而非依赖药物特征。
  • 在未见药物对上性能显著提升,严格分离测试集上效果更优。
  • 适合需要真实场景泛化的药物研发与临床安全评估人员。

药物-药物相互作用(DDI)预测是药物发现和临床开发的核心,尤其在多药联用日益普遍的背景下。现有计算方法在标准基准上表现良好,但在实际部署中往往难以泛化,因为多数候选药物对包含未见过的药物,且已验证的相互作用稀少。我们发现,当前以分子为中心的模型中,嵌入空间的接近度与实际交互标签无可靠关联,单纯扩大模型容量无法提升泛化能力。为此,我们提出GenRel-DDI,一种关系中心化的可泛化关系学习框架,将DDI预测重构为不依赖药物身份的关系表示学习问题。这种关系层面的抽象能够捕捉可迁移的交互模式,从而推广至未见药物和新药对。在多个基准上的实验表明,GenRel-DDI持续显著优于现有最优方法,尤其在严格的实体不交集评估中表现突出,证明了关系学习在鲁棒DDI预测中的有效性和实用性。代码开源:https://github.com/SZU-ADDG/GenRel-DDI。

原文摘要 · Abstract (English)

Drug-drug interaction (DDI) prediction is central to drug discovery and clinical development, particularly in the context of increasingly prevalent polypharmacy. Although existing computational methods achieve strong performance on standard benchmarks, they often fail to generalize to realistic deployment scenarios, where most candidate drug pairs involve previously unseen drugs and validated interactions are scarce. We demonstrate that proximity in the embedding spaces of prevailing molecule-centric DDI models does not reliably correspond to interaction labels, and that simply scaling up model capacity therefore fails to improve generalization. To address these limitations, we propose GenRel-DDI, a generalizable relation learning framework that reformulates DDI prediction as a relation-centric learning problem, in which interaction representations are learned independently of drug identities. This relation-level abstraction enables the capture of transferable interaction patterns that generalize to unseen drugs and novel drug pairs. Extensive experiments across multiple benchmark demonstrate that GenRel-DDI consistently and significantly outperforms state-of-the-art methods, with particularly large gains on strict entity-disjoint evaluations, highlighting the effectiveness and practical utility of relation learning for robust DDI prediction. The code is available at https://github.com/SZU-ADDG/GenRel-DDI.

药物相互作用关系学习泛化能力

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