Enhancing Tree-Based Machine Learning for Personalized Drug Assignment

Personalized drug selection is crucial for treating complex diseases such as Acute Myeloid Leukemia, where maximizing therapeutic efficacy is essential. Although precision medicine aims to tailor treatments to individual molecular profiles, existing machine learning models often fall short in selecting the best drug from multiple candidates. We present SEATS (Systematic Efficacy Assignment with Treatment Seats), which adapts conventional models like Random Forest and XGBoost for multiclass drug assignment by allocating probabilistic “treatment seats” to drugs based on efficacy. This approach helps models learn clinically relevant distinctions. Additionally, we assess an interpretable Optimal Decision Tree (ODT) model designed specifically for drug assignment. Trained on the BeatAML2 cohort and validated on the GDSC AML cell line dataset, integrating SEATS with Random Forest and XGBoost improved prediction accuracy and consistency. The ODT model offered competitive performance with clear, interpretable decision paths and minimal feature requirements, facilitating clinical use. SEATS reorients standard models towards personalized drug selection. Combined with the ODT framework it provides effective, interpretable strategies for precision oncology, underscoring the potential of tailored machine learning solutions in supporting real-world treatment decisions.