BackgroundIn many applications of bioinformatics, data stem from distinct heterogeneous sources. One of the well-known examples is the identification of drug–target interactions (DTIs), which is of significant importance in drug discovery. In this paper, we propose a novel framework, manifold optimization based kernel preserving embedding (MOKPE), to efficiently solve the problem of modeling heterogeneous data. Our model projects heterogeneous drug and target data into a unified embedding space by preserving drug–target interactions and drug–drug, target–target similarities simultaneously.ResultsWe performed ten replications of ten-fold cross validation on four different drug–target interaction network data sets for predicting DTIs for previously unseen drugs. The classification evaluation metrics showed better or comparable performance compared to previous similarity-based state-of-the-art methods. We also evaluated MOKPE on predicting unknown DTIs of a given network. Our implementation of the proposed algorithm in R together with the scripts that replicate the reported experiments is publicly available athttps://github.com/ocbinatli/mokpe.