Interpretable Feature Interaction Mining in High-Dimensional Clinical Data Using Hybrid Tree–Neural Models

High-dimensional clinical data exhibit complex and non-linear relationships among patient attributes, where outcomes are often influenced by feature interactions rather than isolated variables. However, many existing machine learning models prioritize predictive performance while providing limited interpretability and insufficient insight into interaction structures. This study aims to address this limitation by developing an interpretable and robust framework for feature interaction mining in clinical data. We propose a hybrid tree–neural modeling framework that explicitly captures and ranks feature interactions while maintaining stable predictive performance. Tree-based ensemble models are employed to identify non-linear interaction patterns, while neural representations enhance learning flexibility and generalization. The framework integrates interaction importance analysis, cross-validation–based stability assessment, and evaluation across multiple data splits to ensure robustness and interpretability. Experiments conducted on a real-world high-dimensional clinical dataset demonstrate that the proposed approach achieves consistent predictive performance, with AUC values ranging from 0.628 to 0.641 across five cross-validation folds (mean AUC ≈ 0.633). Performance remains stable under varying train–test splits, indicating strong generalizability. Interaction analysis reveals that a small number of dominant feature interactions—such as age combined with length of hospital stay and medication count combined with diagnostic information—consistently contribute to model predictions, appearing in over 80% of validation folds. Ablation studies further confirm that removing interaction-aware components leads to noticeable performance degradation, highlighting their importance.  In conclusion, this study demonstrates that explicit feature interaction modeling enhances interpretability, stability, and generalization in clinical prediction tasks. The proposed hybrid framework provides a reliable foundation for developing trustworthy and transparent clinical decision-support systems