自动构建可解释的心脏影像复合表型,提升疾病关联分析效果。
CPAgents: Agentic Composite Phenotype Generation for Cardiac Disease Association

- 三智能体协作自动生成多项式、比值等复合表型
- 在72组对比中56次领先基线,9类疾病均表现更优
- 结果可解释且有透明证据链,适合临床研究与风险分层
识别心脏影像表型与临床疾病之间的稳健关联,是大规模心血管研究和可靠风险分层的基础。然而,现有表型全基因组关联研究依赖预定义的单一变量表型或专家设计特征,难以捕捉临床相关的非线性效应和跨表型交互。为此,我们提出CPAgents,一种用于心血管表型全基因组关联研究(PheWAS)的迭代表型组合框架,可从基础影像特征自动构建并验证可解释的复合表型(如多项式、比值、交互形式)。系统由三个智能体协同:(i) 分析师识别统计异常并提名候选变换;(ii) 提议者在数值安全规则下生成医学与统计上合理的表达式;(iii) 验证者通过多阶段标准评估候选项,并为通过的表型生成透明证据链。在大规模心脏影像队列上评估,所发现的复合表型显著提升疾病区分能力:在72个分类器-疾病-指标组合中,我们的变体在56次中排名第一,而基线仅18次,所有九类临床疾病均观察到性能提升。该框架产出简洁、临床可解释的表型公式,具备透明证据链,推动超越专家驱动特征选择的更强表型-疾病关联发现。
原文摘要 · Abstract (English)
Identifying robust associations between cardiac imaging phenotypes and clinical diseases is fundamental to population-scale cardiovascular research and reliable risk stratification. However, current phenome-wide association studies rely on pre-defined, single-variable phenotypes or expert-crafted features, which limits their ability to capture clinically meaningful non-linear effects and cross-phenotype interactions. To address this, we propose CPAgents, an iterative phenotype-Composition framework for cardiovascular Phenome-wide association study (PheWAS) that automatically constructs and validates interpretable composite phenotypes (e.g., polynomial, ratio, and interaction forms) from base imaging features. Specifically, our system coordinates three agents: (i) an Analyst that identifies statistical pathologies and nominates candidate transformations; (ii) a Proposer that generates constrained, medically and statistically motivated expressions under numerical safety rules; and (iii) a Verifier that evaluates candidates using multi-stage criteria and produces transparent evidence trails for accepted phenotypes. Evaluated on a population-scale cardiac imaging cohort, the discovered composite phenotypes markedly improve disease discrimination: across 72 classifier-disease-metric combinations, our variants achieve the top rank in 56 cases versus 18 for baselines, with gains observed across all nine clinical disease categories. Our framework yields compact, clinically interpretable phenotype formulas with transparent evidence trails, enabling scalable discovery of stronger phenotype-disease associations beyond expert-driven feature selection.
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