From Latent Biomarkers to Clinical Rules: Embedding-Guided Rule Mining and Attribution-Based Translation for Interpretable Tabular Learning

Predictive modeling for clinical decision support requires both strong predictive performance and transparent, auditable, and human-reviewable decision logic. Although deep learning and tree-based ensemble methods can achieve high accuracy, their black-box nature remains a major obstacle to trustworthy clinical deployment. Moreover, clinical prediction often operates under practical constraints, including limited sample sizes, severe class imbalance, and feature evolution arising from changes in diagnostic criteria or clinical documentation practices. We propose Medical Heuristic Learning (MHL), a constrained paradigm for LLM-assisted rule learning. Rather than relying on updates to implicit model weights, MHL integrates statistical probes, medical knowledge probes, initial rule synthesis, and iterative rule optimization to construct an executable rule-based expert system. The resulting rule system is expressed entirely using the native logical and control-flow constructs of a programming language. Valid rule versions are recorded and retained along the search trajectory, making the decision logic explicit, interpretable, and auditable. MHL also supports continual learning by using previously validated rules as a starting point and iteratively revising them in response to updated feature information under data drift or feature evolution. MHL is not tied to any specific programming language. Comprehensive experiments on medical datasets show that MHL achieves predictive performance comparable to that of state-of-the-art methods, performs favorably in small-sample and highly imbalanced settings, and supports the transfer and adaptive revision of validated rules under feature evolution. Overall, these findings suggest that non-gradient-based heuristic systems offer an approach to balancing predictive performance and transparency in clinical decision support.

In clinical tabular prediction, classical machine learning models with feature engineering often outperform neural methods. LLMs are increasingly used to automate this process, acting as domain experts that propose diverse feature transformations to boost downstream performance. However, the feature generation process of existing LLM-based methods is agnostic to the downstream learner: the LLM receives no signal about which features currently drive predictions or where the model's representational capacity falls short, so proposals are neither targeted to promising regions of the feature space nor tailored to the learner's inductive bias. This shortcoming is amplified in healthcare data, which simultaneously exhibits class imbalance, heterogeneous feature spaces, and strict interpretability requirements. In this paper, we propose MedFeat, the first feature engineering framework inspired by the workflow of machine learning practitioners, leveraging model-awareness and feature importance signals to iteratively guide feature discovery for clinical tabular learning. We evaluate MedFeat on a broad range of challenging real-world clinical tasks and show that it statistically significantly outperforms state-of-the-art baselines, with an average F1 improvement of more than 10% over the baseline across models with distinct inductive biases.

This study compares traditional machine learning models and Large Language Model (LLM)-generated rule-based systems for heart disease prediction using the UCI Heart Disease dataset. Several classifiers, including Logistic Regression, K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Naive Bayes, Decision Tree, and Random Forest, were evaluated alongside rule-based systems generated using GPT-4o and Claude Sonnet 4.6. Model performance was assessed using accuracy, precision, recall, and F1-score metrics. Experimental results show that traditional machine learning models consistently outperform LLM-generated rule-based systems in predictive performance. Random Forest achieved the best overall performance with 90.2% accuracy, a precision of 0.829, perfect recall of 1.0, and an F1-score of 0.906. Naive Bayes followed closely with 88.5% accuracy and an F1-score of 0.881. In contrast, the LLM-generated rule models achieved lower performance, with Claude Sonnet 4.6 reaching 80.3% accuracy (F1-score: 0.833) and GPT-4o obtaining 70.5% accuracy (F1-score: 0.690). Despite the performance gap, the LLM-generated rules provide interpretable IF-THEN diagnostic logic that enhances explainability and transparency in clinical decision-making. These findings highlight the trade-off between predictive performance and interpretability in medical artificial intelligence systems. The complete implementation of all experiments, including machine learning models and LLM-derived rule classifiers, is publicly available in the GitHub repository at https://github.com/FeisalAlaswad/LLM-Rule-ML-Heart-Disease-Prediction .