将泛化医学知识转化为可验证的具体假设,提升科研可解释性。
Can Broad Biomedical Knowledge be Contextualized into Scenario-Grounded Propositions?

- 用双层多智能体框架迭代搜索,把知识转为可落地的命题
- 在临床试验中发现有治疗差异的患者亚群,效果优于现有方法
- 适合需要可解释性假设的医学研究者,尤其擅长精准医疗场景
生物医学发现常需连接泛化知识与具体实验或临床数据。背景知识虽能提示相关机制,但过于宽泛,难以直接映射到数据变量;而数据驱动模式又常局限于特定数据集,机制解释性差。本文将这一缺失环节定义为知识情境化:将广泛医学知识转化为证据支持、场景适配的命题,供领域专家检查、复现和验证。提出SCENE框架,采用双层多智能体设计,上层将知识转化为搜索方向并锚定至数据结构,下层通过多目标优化执行搜索,生成兼顾证据强度与数据支持的明确命题。两层间反馈持续优化。在两类场景评估:临床试验中识别治疗受益异质的患者亚群,及LINCS L1000研究中发现上下文相关的生物学响应。结果表明,SCENE能有效连接泛化知识与具体证据,生成可追溯、可检验的假设,适用于后续验证。
原文摘要 · Abstract (English)
Biomedical discovery often requires connecting broad biomedical knowledge with specific experimental or clinical data. Background knowledge suggests relevant mechanisms but is usually too general to map directly onto dataset variables, while data-driven patterns can be dataset-specific and hard to interpret mechanistically. We study this missing link as knowledge contextualization: transforming broad biomedical knowledge into evidence-supported, scenario-grounded propositions that domain experts can inspect, replay, and validate. We propose SCENE, a bi-level multi-agent framework that treats knowledge contextualization as iterative search. The upper level converts broad knowledge into search directions and grounds them in the dataset schema. The lower level executes these directions through multi-objective optimization to identify concrete propositions that balance evidential strength and data support. Feedback between the two levels progressively refines the search. We evaluate SCENE in two settings: discovering patient subgroups with heterogeneous treatment benefits in clinical trial scenarios, and identifying context-specific biological responses in LINCS L1000 studies. In clinical trials, SCENE discovers specific, well-supported subgroups and outperforms existing baselines. In L1000 studies, SCENE identifies perturbational contexts with strong target-response matching and high positive rates. These results show that SCENE bridges broad knowledge and scenario-specific evidence, producing traceable, inspectable hypotheses for follow-up validation.
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。