Inferring Synergistic Drug Combinations Based on Symmetric Meta-Path in a Novel Heterogeneous Network

Combinatorial drug therapy is a promising way for treating cancers, which can reduce drug side effects and improve drug efficacy. However, due to the large-scale combinatorial space, it is difficult to quickly and effectively identify novel synergistic drug combinations for further implementing combinatorial drug therapy. The computational method of fusing multi-source knowledge is a time- and cost-efficient strategy to infer synergistic drug combinations for testing. However, for the existing computational methods of inferring synergistic drug combinations, it still remains a challenging to effectively combine multi-source information to achieve the desired results. Hence, in this study, we developed a novel Inference method of Synergistic Drug Combinations based on Symmetric Meta-Path (ISDCSMP), which can systematically and accurately prioritize synergistic drug combinations in a novel drug-target heterogeneous network integrating multi-source information. In the experiment, ISDCSMP outperformed the state-of-the-art methods in terms of AUC and precision on the benchmark dataset in five-fold cross validation. Moreover, we further illustrated performances of different ways for obtaining the combination coefficients, and analyzed the influences of the maximum meta-path length. The performances of various single meta-paths were described in five-fold cross validation. Finally, we confirmed the practical usefulness of ISDCSMP with the predicted novel synergistic drug combinations. The source code of ISDCSMP is available at https://github.com/KDDing/ISDCSMP.