DeSIDE-DDI: interpretable prediction of drug-drug interactions using drug-induced gene expressions

• Published in: Journal of cheminformatics Vol. 14; no. 1; p. 9
• Main Authors: Kim, Eunyoung, Nam, Hojung
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 04.03.2022; BioMed Central Ltd; BMC
• Subjects: Chemistry; Chemistry and Materials Science; Complications and side effects; Computational Biology/Bioinformatics; Computer Applications in Chemistry; Deep learning; Documentation and Information in Chemistry; Drug discovery; Drug-drug interaction; Gene expression; Genes; In silico prediction; Polypharmacy side effects; Research Article; Theoretical and Computational Chemistry; United Kingdom; Deep learning; Drug-drug interaction; Polypharmacy side effects; In silico prediction
• ISSN: 1758-2946; 1758-2946
• DOI: 10.1186/s13321-022-00589-5

Adverse drug-drug interaction (DDI) is a major concern to polypharmacy due to its unexpected adverse side effects and must be identified at an early stage of drug discovery and development. Many computational methods have been proposed for this purpose, but most require specific types of information, or they have less concern in interpretation on underlying genes. We propose a deep learning-based framework for DDI prediction with drug-induced gene expression signatures so that the model can provide the expression level of interpretability for DDIs. The model engineers dynamic drug features using a gating mechanism that mimics the co-administration effects by imposing attention to genes. Also, each side-effect is projected into a latent space through translating embedding. As a result, the model achieved an AUC of 0.889 and an AUPR of 0.915 in unseen interaction prediction, which is competitively very accurate and outperforms other state-of-the-art methods. Furthermore, it can predict potential DDIs with new compounds not used in training. In conclusion, using drug-induced gene expression signatures followed by gating and translating embedding can increase DDI prediction accuracy while providing model interpretability. The source code is available on GitHub ( https://github.com/GIST-CSBL/DeSIDE-DDI ).