# CPAgents: Agentic Composite Phenotype Generation for Cardiac Disease Association

arXiv: https://arxiv.org/abs/2606.28179 · HTML: https://mlsanity.com/paper/2606.28179/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 7 of its 19 references that are in the map.
- First posted on arXiv 26 Jun 2026.

## Builds on (most cited first, 7 of 7)

- [A Unified Approach to Interpreting Model Predictions](https://mlsanity.com/paper/1705.07874/) (2017)
- [DeepSeek-V3.2: Pushing the Frontier of Open Large Language Models](https://mlsanity.com/paper/2512.02556/) (2025)
- [MedAgent-Pro: Towards Evidence-based Multi-modal Medical Diagnosis via Reasoning Agentic Workflow](https://mlsanity.com/paper/2503.18968/) (2025)
- [MedRAX: Medical Reasoning Agent for Chest X-ray](https://mlsanity.com/paper/2502.02673/) (2025)
- [LLM-FE: Automated Feature Engineering for Tabular Data with LLMs as Evolutionary Optimizers](https://mlsanity.com/paper/2503.14434/) (2025)
- [AutoQual: An LLM Agent for Automated Discovery of Interpretable Features for Review Quality Assessment](https://mlsanity.com/paper/2510.08081/) (2025)
- [Multi-Agent Reasoning for Cardiovascular Imaging Phenotype Analysis](https://mlsanity.com/paper/2507.03460/) (2025)

## Abstract (arXiv)

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.