Reverse tracking from drug-induced transcriptomes through multilayer molecular networks reveals hidden drug targets

Highlights

• Drug targets cause gene transcriptional change after drug treatment through molecular processes.

• Reverse tracking from genes to proteins in the multilayer network finds drug targets.

• The model shows better performance in predicting drug targets and suggests molecular mechanisms.

• The model is especially useful in the absence of the reliable structure of target proteins or drugs.

Abstract

Identifying molecular targets of a drug is an essential process for drug discovery and development. The recent in-silico approaches are usually based on the structure information of chemicals and proteins. However, 3D structure information is hard to obtain and machine-learning methods using 2D structure suffer from data imbalance problem. Here, we present a reverse tracking method from genes to target proteins using drug-perturbed gene transcriptional profiles and multilayer molecular networks. We scored how well the protein explains gene expression changes perturbed by a drug. We validated the protein scores of our method in predicting known targets of drugs. Our method performs better than other methods using the gene transcriptional profiles and shows the ability to suggest the molecular mechanism of drugs. Furthermore, our method has the potential to predict targets for objects that do not have rigid structural information, such as coronavirus.