DrugCom: Synergistic Discovery of Drug Combinations Using Tensor Decomposition

Abstract

Personalized treatments and targeted therapies are the most promising approaches to treat complex diseases, especially for cancer. However, drug resistance is often acquired after treatments. To overcome or reduce drug resistance, treatments using drug combinations have been actively investigated in the literature. Existing methods mainly focus on chemical properties of drugs for potential combination therapies without considering relationships among different diseases. Also, they often do not consider the rich knowledge of drugs and diseases, which can enhance the prediction of drug combinations. This motivates us to develop a new computational method that can predict the beneficial drug combinations. We propose DrugCom, a tensor-based framework for computing drug combinations across different diseases by integrating multiple heterogeneous data sources of drugs and diseases. DrugCom first constructs a primary third-order tensor (i.e., drug×drug ×disease) and several similarity matrices from multiple data sources regarding drugs (e.g., chemical structure) and diseases (e.g., disease phenotype). DrugCom then formulates an objective function, which simultaneously factorizes coupled tensor and matrices to reveal the molecular mechanisms of drug synergy. We adopt the alternating direction method of multipliers algorithm to effectively solve the optimization problem. Extensive experimental studies using real-world datasets demonstrate superior performance of DrugCom.