arXiv:2511.06662cs.LGq-bio.QM2025-11

融合病历与药物知识图谱,实现未知药物相互作用的零样本预测。

Dual-Pathway Fusion of EHRs and Knowledge Graphs for Predicting Unseen Drug-Drug Interactions

  • 双路径融合:用患者病历上下文优化知识图谱关系评分
  • 学生模型仅依赖病历即可零样本预测新药相互作用,精度更高
  • 可解释机制预警,适合临床决策支持与药物警戒场景

药物相互作用(DDI)仍是可预防伤害的主要来源,许多临床重要机制尚不明确。现有模型或依赖药理知识图谱(KG),难以处理未见药物;或基于电子健康记录(EHR),存在噪声大、时序性强、机构依赖等问题。本文首次提出一种系统,将知识图谱关系评分条件化于患者级EHR上下文,并将该推理过程蒸馏为仅需EHR的“学生”模型,实现零样本推断。教师模型在双重数据源中学习特定机制的药物对关系,学生模型则无需知识图谱即可泛化至新药或罕见药物。两者共享一组药理学机制(药物关系)本体,生成可解释、可审计的警示而非黑箱风险评分。模型在多机构EHR语料库与经整理的DrugBank DDI图上训练,采用符合临床决策、防泄漏负样本的评估协议。结果表明,系统在多机构测试数据上保持高精度,产生机制特定且临床一致的预测,相比先前方法显著降低误报率(提升精度),同时在整体检测性能(F1)相当的情况下漏检更少。案例研究进一步验证了对未出现在知识图谱中的药物,成功识别出公认的CYP介导及药效学机制,支持其在临床决策支持与药物警戒中的实际应用。

原文摘要 · Abstract (English)

Drug-drug interactions (DDIs) remain a major source of preventable harm, and many clinically important mechanisms are still unknown. Existing models either rely on pharmacologic knowledge graphs (KGs), which fail on unseen drugs, or on electronic health records (EHRs), which are noisy, temporal, and site-dependent. We introduce, to our knowledge, the first system that conditions KG relation scoring on patient-level EHR context and distills that reasoning into an EHR-only model for zero-shot inference. A fusion "Teacher" learns mechanism-specific relations for drug pairs represented in both sources, while a distilled "Student" generalizes to new or rarely used drugs without KG access at inference. Both operate under a shared ontology (set) of pharmacologic mechanisms (drug relations) to produce interpretable, auditable alerts rather than opaque risk scores. Trained on a multi-institution EHR corpus paired with a curated DrugBank DDI graph, and evaluated using a clinically aligned, decision-focused protocol with leakage-safe negatives that avoid artificially easy pairs, the system maintains precision across multi-institutuion test data, produces mechanism-specific, clinically consistent predictions, reduces false alerts (higher precision) at comparable overall detection performance (F1), and misses fewer true interactions compared to prior methods. Case studies further show zero-shot identification of clinically recognized CYP-mediated and pharmacodynamic mechanisms for drugs absent from the KG, supporting real-world use in clinical decision support and pharmacovigilance.

药物相互作用知识图谱零样本临床决策

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