Hybrid feature-selection and diversity-guided stacking framework for interpretable ensemble learning: Application to COVID-19 mortality prediction

Farideh Mohtasham, Seyed Saeed Hashemi Nazari, Mohamad Amin Pourhoseingholi, Kaveh Kavousi and Mohammad Reza Zali

PLOS ONE, 2026, vol. 21, issue 4, 1-28

Abstract: Background: Reliable predictive modeling in high-dimensional biomedical data requires a balance between accuracy, interpretability, and computational efficiency. However, existing ensemble methods often overlook model diversity or rely on ad hoc feature-selection approaches, which limit generalizability. This study introduces a hybrid feature-selection and diversity-guided stacking framework designed to improve robustness and scalability across clinical and other data-intensive domains. Methods: The proposed framework integrates a hybrid feature-selection pipeline—combining Variance Inflation Factor (VIF), Analysis of Variance (ANOVA), Sequential Backward Elimination (SBE), and Lasso regression—to reduce multicollinearity and overfitting. It also employs a diversity-aware stacking strategy that constructs sub-model sets based on pairwise diversity measures (Disagreement, Yule’s Q, and Cohen’s Kappa) and non-pairwise metrics (Entropy and Kohavi–Wolpert). Sixteen base classifiers and five meta-learners were trained using repeated 10-fold cross-validation. The framework was evaluated using data from 4,778 hospitalized COVID-19 patients with 116 clinical and laboratory attributes, preprocessed using robust scaling and ROSE-based class balancing. Results: The optimal configuration, which stacked Random Forest and XGBoost models using a Neural Network meta-learner, achieved 91.4% accuracy (95% CI: 89.8–92.8), AUC = 0.955, F1 = 0.801, and MCC = 0.746, outperforming the best individual model (AdaBoost, 90.2%). Training time (~450 s) and per-case inference time (

Date: 2026
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0341198

DOI: 10.1371/journal.pone.0341198

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