Exploring feature limitations in antimicrobial resistance prediction: machine learning and deep learning in A. baumannii

Antimicrobial resistance phenotype prediction (AMRPP) provides a computational alternative to conventional susceptibility testing. While most studies focus on single antibiotics, systematic multi-antibiotic modeling and optimal strain representation remain underexplored. Acinetobacter baumannii (A. baumannii), designated by the World Health Organization as a critical priority pathogen, still lacks a comprehensive computational investigation. This study introduces a multi-antibiotic framework for AMRPP in A. baumannii, in which strains are encoded by gene presence/ absence (GPA) profiles. We evaluate whether these features contain sufficient predictive information for classical machine learning (ML) models or require advanced deep learning (DL) architectures. To enhance the representational informativeness and mitigate the high dimensionality of GPA features, four strategies are applied: pathway-based filtering using KEGG, statistical selection by information content (IC), unsupervised reduction via PCA, and model-driven explainability selection with SHAP. Moreover, strong ML baselines: support vector machines, random forests, and extreme gradient boosting (XGB), are benchmarked against a custom DL model, TripSimAcin-AMR, a three-subnetwork siamese neural network tailored for limited data. According to the results, Data-driven representations (PCA, IC, SHAP) outperform KEGG-based filtering, achieving an overall performance of 92.64-93.16%. TripSimAcin-AMR and XGB yield comparable accuracy, but TripSimAcin-AMR achieves higher specificity (85.17% vs. 78.77%). From a clinical perspective, this high specificity is particularly crucial, as false-positive resistance predictions can mislead clinicians to avoid effective first-line antibiotics and unnecessarily escalate to broad-spectrum or last-line therapies. The best configuration, TripSimAcin-AMR with IC-based features, reaches 94.2% accuracy, 94.2% AUC-ROC, 97.0% sensitivity, and 91.3% specificity, underscoring the potential of enriched GPA representations for robust AMR prediction.