arXiv:2608.05982cs.LGq-bio.QM2026-08

构建时间感知的生物医学知识图谱,预测药物研发能否进入下一阶段。

THBKG: A Temporal Biomedical Knowledge Graph for Decision-Aligned Clinical Advancement Prediction

论文配图:THBKG: A Temporal Biomedical Knowledge Graph for Decision-Aligned Clinical Advancement Prediction
图 1 · 摘自论文原文
  • 基于历史证据时间点构建动态知识图谱,还原决策时的真实证据状态。
  • 在无直接证据的72.8%组合中仍实现五到六倍于随机水平的预测准确率。
  • 支持可解释性分析,适合药物研发决策与靶点评估研究者使用。

40%-50%的二期临床试验失败源于靶点-疾病关联不足,提前预测研发项目是否推进可帮助药企聚焦高潜力方案。关键在于判断项目进入临床时所依赖的证据状况。现有生物医学知识图谱无法追溯某一历史时间点的证据构成。本文提出时序异构生物医学知识图谱(THBKG),包含110,396个实体、1110万条边,覆盖19种关系类型,每条边附带证据更新年份,可精准重建任一靶点-疾病对在进入二期时的证据状态。在此基础上定义决策对齐基准,预测靶点-疾病对在进入二期时是否会推进至三期,仅依赖该时间点前的证据。基于THBKG的图传播模型在同协议下超越所有直接证据参考方法,在每个治疗领域前10名预测中相对提升4.3%-4.5%。尤其在72.8%缺乏直接证据的组合上,直接边模型无法读取信息,而图模型仍显著优于随机水平,通过传播中间生物学信号恢复有效预测。采用路径解释器分析决策子图,揭示预测背后的证据结构,实现可解释预测。我们公开发布持续更新的THBKG,为回溯验证治疗靶点假说提供基础平台。

原文摘要 · Abstract (English)

Inadequate target--disease linkage accounts for 40--50\% of Phase~II efficacy failures, so anticipating which programmes will advance would let sponsors back the hypotheses most likely to reach patients. What a programme can be judged on is the evidence that supported its linkage \emph{when it entered the clinic}. No existing biomedical knowledge graph allows that evidence profile to be assembled as of a past date. We present the Temporal Heterogeneous Biomedical Knowledge Graph (THBKG), which describes and predicts therapeutic target--disease links through time: 110,396 entities and 11.1M edges across nineteen relation types, each edge carrying the year its evidence changed, so a pair's profile can be recovered as it stood when its own decision fell due. On this graph we define a decision-aligned benchmark that predicts, for a target--disease pair entering Phase~II, whether it advances to Phase~III on evidence datable before that decision. Graph propagation over the THBKG outranks every direct-evidence reference scored under the same decision-aligned protocol, reaching a relative success of 4.3--4.5 at the top ten pairs per therapeutic area. The gain concentrates on the 72.8\% of pairs with no direct target--disease evidence at their decision point, where a direct-edge model has nothing to read: the encoders still rank five- to sixfold above chance, recovering the signal by propagating over the intervening biology. Adapting a path-based explainer to the decision-time subgraph decomposes each prediction into the evidence landscape behind the hypothesis for explainable prediction. We release the THBKG as a continually updated substrate for studying therapeutic target hypotheses by retrospective validation.

知识图谱药物研发可解释性时序建模

Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。