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    This study introduces a machine learning framework combining feature selection and data augmentation for accurate and interpretable omics-based classification, even with limited patient samples.

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    Area of Science:

    • Bioinformatics
    • Computational Biology
    • Machine Learning in Healthcare

    Background:

    • Omics datasets present challenges in classification due to high dimensionality and limited samples.
    • Current models often lack interpretability, hindering trust and reproducibility in clinical applications.

    Purpose of the Study:

    • To develop a machine learning framework integrating feature selection and data augmentation for improved omics-based classification.
    • To enhance model transparency and reliability in disease classification using omics data.

    Main Methods:

    • A machine learning pipeline combining feature selection with data augmentation techniques.
    • Bootstrap analysis on the E-MTAB-8026 dataset across six binary classification scenarios.
    • Evaluation of cross-validated performance and generalization to larger test sets.

    Main Results:

    • The proposed framework achieves high classification accuracy and improved interpretability.
    • Cross-validated performance on small datasets was maintained when applied to larger test sets.
    • Synthetic data augmentation positively impacted model generalization, especially with limited sample availability.

    Conclusions:

    • The framework offers a balance between accuracy and feature selection for reliable omics-based classification.
    • Data augmentation is crucial for enhancing generalization in omics studies with scarce data.
    • This approach supports the development of explainable, reproducible diagnostic tools for clinical decision-making.