Enhancing Generalization in Sickle Cell Disease Diagnosis through Ensemble Methods and Feature Importance Analysis

Nataša Petrović, Gabriel Moyà-Alcover, Antoni Jaume-i-Capó, Jose Maria Buades Rubio
1/19/2026
cs.LG

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Abstract

This work presents a novel approach for selecting the optimal ensemble-based classification method and features with a primarly focus on achieving generalization, based on the state-of-the-art, to provide diagnostic support for Sickle Cell Disease using peripheral blood smear images of red blood cells. We pre-processed and segmented the microscopic images to ensure the extraction of high-quality features. To ensure the reliability of our proposed system, we conducted an in-depth analysis of interpretability. Leveraging techniques established in the literature, we extracted features from blood cells and employed ensemble machine learning methods to classify their morphology. Furthermore, we have devised a methodology to identify the most critical features for classification, aimed at reducing complexity and training time and enhancing interpretability in opaque models. Lastly, we validated our results using a new dataset, where our model overperformed state-of-the-art models in terms of generalization. The results of classifier ensembled of Random Forest and Extra Trees classifier achieved an harmonic mean of precision and recall (F1-score) of 90.71\% and a Sickle Cell Disease diagnosis support score (SDS-score) of 93.33\%. These results demonstrate notable enhancement from previous ones with Gradient Boosting classifier (F1-score 87.32\% and SDS-score 89.51\%). To foster scientific progress, we have made available the parameters for each model, the implemented code library, and the confusion matrices with the raw data.

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@article{petrovi2026enhancing,
  title  = {Enhancing Generalization in Sickle Cell Disease Diagnosis through Ensemble Methods and Feature Importance Analysis},
  author = {Nataša Petrović and Gabriel Moyà-Alcover and Antoni Jaume-i-Capó and Jose Maria Buades Rubio},
  year   = {2026},
  eprint = {2601.13021},
  archivePrefix = {arXiv},
  url    = {http://arxiv.org/abs/2601.13021v1}
}

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