用生物通路知识图谱让抗药性预测结果可解释
KG-TRACE: A Neuro-Symbolic Framework for Mechanistic Grounding in Antimicrobial Resistance Prediction

- 将基因组数据与生物知识图谱通过信任门融合,动态校准神经网络判断
- 对异烟肼预测达0.9760的AUROC,92.5%的预测结果符合已知生物学路径
- 提供可审计的解释链条,适合需要可信决策支持的临床场景
基于全基因组测序的抗微生物药物耐药性(AMR)预测已达到高准确率,但现有模型无法将神经网络的归因结果与已有生物学通路关联。我们提出KG-TRACE,一种新型神经符号框架,将世界卫生组织(WHO)突变知识图谱(KG)作为结构化生物约束,嵌入神经基因组模型。不同于仅学习统计模式的方法,KG-TRACE通过可学习的表征信任门,融合基因组特征与基于RotatE的知识图谱嵌入,动态权衡神经证据与符号生物学知识。在CRyPTIC结核分枝杆菌队列上评估,对异烟肼预测的AUROC达0.9760,虽预测性能具竞争力,但核心价值在于符号化接地。我们引入生物接地率(BGR)这一数据集级指标,量化神经归因与已有生物学的一致性。该框架实现92.5%的异烟肼耐药预测符号覆盖,并通过为'不确定'案例发出实验室复核提示,有效识别多重耐药共现伪影。结果表明,神经符号接地可为临床医生提供可验证的审计追踪,弥合预测准确率与临床信任之间的鸿沟。
原文摘要 · Abstract (English)
While WGS-based AMR prediction has reached high accuracy, existing models lack a mechanism to ground neural attributions in established biological pathways. We present KG-TRACE, a novel neuro-symbolic framework that integrates the WHO mutation knowledge graph (KG) as a structured biological constraint on a neural genomic model. Unlike existing methods that learn statistical patterns in isolation, KG-TRACE fuses genomic features and RotatE-based KG embeddings through a learned epistemic trust gate, dynamically weighting neural evidence against symbolic biological knowledge. Evaluated on the CRyPTIC M. tuberculosis cohort, KG-TRACE achieves an AUROC of 0.9760 for isoniazid, achieving competitive accuracy while its primary value lies in symbolic grounding, not predictive uplift. More importantly, we introduce the Biological Grounding Ratio (BGR), a dataset-level metric that quantifies alignment between neural attributions and established biology. Our framework achieves a 92.5% symbolic coverage of isoniazid-resistant predictions and effectively identifies MDR co-occurrence artifacts by issuing laboratory follow-up flags for 'UNCERTAIN' cases. We demonstrate that neuro-symbolic grounding provides a verifiable audit trail for clinicians, bridging the gap between predictive accuracy and clinical trust.
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