CFSSynergy: Combining Feature-Based and Similarity-Based Methods for Drug Synergy Prediction.

Drug synergy prediction plays a vital role in cancer treatment. Because experimental approaches are labor-intensive and expensive, computational-based approaches get more attention. There are two types of computational methods for drug synergy prediction: feature-based and similarity-based. In feature-based methods, the main focus is to extract more discriminative features from drug pairs and cell lines to pass to the task predictor. In similarity-based methods, the similarities among all drugs and cell lines are utilized as features and fed into the task predictor. In this work, a novel approach, called CFSSynergy, that combines these two viewpoints is proposed. First, a discriminative representation is extracted for paired drugs and cell lines as input. We have utilized transformer-based architecture for drugs. For cell lines, we have created a similarity matrix between proteins using the Node2Vec algorithm. Then, the new cell line representation is computed by multiplying the protein-protein similarity matrix and the initial cell line representation. Next, we compute the similarity between unique drugs and unique cells using the learned representation for paired drugs and cell lines. Then, we compute a new representation for paired drugs and cell lines based on the similarity-based features and the learned features. Finally, these features are fed to XGBoost as a task predictor. Two well-known data sets were used to evaluate the performance of our proposed method: DrugCombDB and OncologyScreen. The CFSSynergy approach consistently outperformed existing methods in comparative evaluations. This substantiates the efficacy of our approach in capturing complex synergistic interactions between drugs and cell lines, setting it apart from conventional similarity-based or feature-based methods.