ComplexMatrixComb: Predicting Drug Combination IC ₅₀ Doses via Complex Numbers and Matrix Factorization

Determining precise drug concentrations to inhibit cancer cell growth is a critical but resource-intensive challenge, especially for combinations requiring many dose pairs. Existing computational methods often predict synergy or classify interactions but rarely estimate exact concentration pairs for a defined inhibitory effect. We introduce ComplexMatrixComb, a matrix factorization framework predicting drug combination dosages achieving IC ₅₀ for specific cancer cell lines. It encodes drug concentrations as real and imaginary components of complex numbers, modeling joint dose–response dynamics and enabling accurate IC ₅₀ estimation. Across O’Neil, NCI-ALMANAC, and AZ-Dream datasets, ComplexMatrixComb outperformed traditional machine learning in regression and classification, showing robustness to drug order and adaptability to varied designs. Integration with models such as ComboFM and ComboLTR showed predicted concentrations closely matched ground-truth doses. Experimental validation of five drug pair–cell line predictions using MTT assays confirmed 50% growth inhibition. By reducing reliance on exhaustive screens, ComplexMatrixComb offers a scalable, data-driven tool to accelerate preclinical research and support personalized oncology strategies.