Abstract
MOTIVATION: Accurate and robust estimation of the synergistic drug combination is important for medicine precision. Although some computational methods have been developed, some predictions are still unreliable especially for the cross-dataset predictions, due to the complex mechanism of drug combinations and heterogeneity of cancer samples. RESULTS: We have proposed JointSyn that utilizes dual-view jointly learning to predict sample-specific effects of drug combination from drug and cell features. JointSyn outperforms existing state-of-the-art methods in predictive accuracy and robustness across various benchmarks. Each view of JointSyn captures drug synergy-related characteristics and makes complementary contributes to the final prediction of the drug combination. Moreover, JointSyn with fine-tuning improves its generalization ability to predict a novel drug combination or cancer sample using a small number of experimental measurements. We also used JointSyn to generate an estimated atlas of drug synergy for pan-cancer and explored the differential pattern among cancers. These results demonstrate the potential of JointSyn to predict drug synergy, supporting the development of personalized combinatorial therapies. AVAILABILITY AND IMPLEMENTATION: Source code and data are available at https://github.com/LiHongCSBLab/JointSyn.