Abstract
Warfarin, a classic oral anticoagulant, is characterized by a narrow therapeutic window and considerable interindividual variability in dosing requirements. This makes precise dose adjustment challenging in clinical practice and increases the risk of bleeding or thrombosis. To improve dose prediction, this study developed a streamlined multilayer perceptron (MLP) model using real-world data from the International Warfarin Pharmacogenomics Consortium (IWPC) database. The LASSO-proj algorithm was applied for high-precision feature selection prior to model construction. The resulting model demonstrated strong predictive performance on the test set, achieving a coefficient of determination ( R (2)) of 0.456, a mean absolute error (MAE) of 8.92 mg/week, and 48.522% of its predictions falling within ±20% of the actual stable therapeutic dose. Through SHAP-based interpretation using DeepExplainer, key features influencing warfarin dosing were identified, including the VKORC1 genotype, body weight, age, and ethnicity. The interpretable MLP framework incorporating LASSO-proj not only maintains high predictive accuracy, but also significantly enhances model transparency, providing a valuable tool for guiding warfarin therapy.