A Machine Learning-Based Biological Drug–Target Interaction Prediction Method for a Tripartite Heterogeneous Network

[Image: see text] Drug repositioning is the identification of interactions between drugs and target proteins in pharmaceutical sciences. Traditional large-scale validation through chemical experiments is time-consuming and expensive, while drug repositioning can drastically decrease the cost and duration taken by traditional drug development. With the rapid advancement of high-throughput technologies and the explosion of various biological and medical data, computational drug repositioning methods have been used to systematically identify potential drug–target interactions. Some of them are based on a particular class of machine learning algorithms called kernel methods. In this paper, we propose a new machine learning prediction method combining multiple kernels into a tripartite heterogeneous drug–target–disease interaction spaces in order to integrate multiple sources of biological information simultaneously. This novel network algorithm extends the traditional drug–target interaction bipartite graph to the third disease layer. Meanwhile, Gaussian kernel functions on heterogeneous networks and the regularized least square method of the Kronecker product are used to predict new drug–target interactions. The values of AUPR (area under the precision–recall curve) and AUC (the area under the receiver operating characteristic curve) of the proposed algorithm are significantly improved. Especially, the AUC values are improved to 0.99, 0.99, 0.97, and 0.96 on four benchmark data sets. These experimental results substantiate that the network topology can be used for predicting drug–target interactions.