Prediction of drug-target interactions from multi-molecular network based on LINE network representation method.

Background: The prediction of potential drug-target interactions (DTIs) not only provides a better comprehension of biological processes but also is critical for identifying new drugs. However, due to the disadvantages of expensive and high time-consuming traditional experiments, only a small section of interactions between drugs and targets in the database were verified experimentally. Therefore, it is meaningful and important to develop new computational methods with good performance for DTIs prediction. At present, many existing computational methods only utilize the single type of interactions between drugs and proteins without paying attention to the associations and influences with other types of molecules.

Methods: In this work, we developed a novel network embedding-based heterogeneous information integration model to predict potential drug-target interactions. Firstly, a heterogeneous multi-molecuar information network is built by combining the known associations among protein, drug, lncRNA, disease, and miRNA. Secondly, the Large-scale Information Network Embedding (LINE) model is used to learn behavior information (associations with other nodes) of drugs and proteins in the network. Hence, the known drug-protein interaction pairs can be represented as a combination of attribute information (e.g. protein sequences information and drug molecular fingerprints) and behavior information of themselves. Thirdly, the Random Forest classifier is used for training and prediction.

Results: In the results, under the five-fold cross validation, our method obtained 85.83% prediction accuracy with 80.47% sensitivity at the AUC of 92.33%. Moreover, in the case studies of three common drugs, the top 10 candidate targets have 8 (Caffeine), 7 (Clozapine) and 6 (Pioglitazone) are respectively verified to be associated with corresponding drugs.

Conclusions: In short, these results indicate that our method can be a powerful tool for predicting potential drug-target interactions and finding unknown targets for certain drugs or unknown drugs for certain targets.