arXiv:2609.06779cs.LGcs.AI2026-09

融合知识图谱与大模型,动态推理药物重定位的机制

DrugReason: Dynamic Multi-View Reasoning over Knowledge Graph and Language Evidence for Drug Repurposing

  • 分角色路由不同推理路径,结合知识图谱与大模型优势
  • 在PharmaDB等数据集上超越单视角基线方法,提升预测准确率
  • 适合需要可解释性药物研发决策的研究者

药物重定位旨在为现有化合物发现新的治疗用途,相比全新药物研发,具有更快、更低成本的优势。然而候选药物-疾病对数量庞大,其潜在关系常依赖复杂的多跳生物机制,难以可靠预测。现有方法分为两类:基于知识图谱的方法将结构化生物证据组织为关系网络,支持可信的多跳推理;基于大模型的方法则利用预训练知识生成灵活的机制解释。但两者各有局限:知识图谱受限于已有结构,大模型缺乏事实依据且易产生幻觉。为此,我们提出DrugReason,一种融合知识图谱与大模型的多视图推理框架,通过上下文感知的动态路由机制,将不同推理路径分配给专用专家,并引入跨专家蒸馏目标实现知识共享而不牺牲专长。在PharmaDB、DDInter和DrugBank上的实验表明,DrugReason在平均性能上优于强基线单视图方法,在与图基方法对比中表现相当或更优,同时提供可解释的路由型预测。

原文摘要 · Abstract (English)

Drug repurposing aims to identify new therapeutic uses for existing compounds and, compared with de novo drug discovery, offers a faster and more cost-effective path to clinical translation. However, the space of candidate drug-disease pairs is enormous and their underlying relationships often depend on complex multi-hop biological mechanisms, making it difficult to reliably predict which pairs represent true therapeutic relationships. Existing approaches tackle this from two directions: knowledge graph-based methods organize curated biomedical evidence into structured relational networks for grounded multi-hop reasoning, while LLM-based methods leverage pretrained knowledge to generate flexible mechanistic rationales. Yet neither is sufficient alone - KGs are confined to observed graph structure while LLMs lack factual grounding and risk hallucination. To address this gap, we propose DrugReason, a multi-view reasoning framework that integrates grounded KG reasoning with LLM-generated mechanistic inference for drug repurposing. DrugReason adaptively routes diverse reasoning paths to specialized experts conditioned on the query context, while a cross-expert distillation objective enables knowledge sharing without sacrificing expert specialization. Experiments on PharmaDB, DDInter, and DrugBank show that DrugReason improves average performance over strong single-view reasoning baselines and achieves competitive or superior results compared with graph-based alternatives, while providing interpretable routing-based predictions.

药物重定位知识图谱大模型推理可解释性

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