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Introduction: Adverse Drug Reactions (ADRs), a widespread phenomenon in clinical drug treatment, are often associated with a high risk of morbidity and even death. Drugs and changes in gene expression are the two important factors that affect whether and how adverse reactions occur. Notably, pharmacogenomics data have recently become more available and could be used to predict ADR occurrence. However, there is a challenge in effectively analyzing the massive data lacking guidance on mutual relationship for ADRs prediction. Methods: We constructed separate similarity features for drugs and ADRs using pharmacogenomics data from the Comparative Toxicogenomics Database CTD, including Chemical-Gene Interactions (CGIs) and Gene-Disease Associations (GDAs). We proposed a novel deep learning architecture, DGANet, based on the constructed features for ADR prediction. The algorithm uses Convolutional Neural Networks (CNN) and cross-features to learn the latent drug-gene-ADR associations for ADRs prediction. Results and Discussion: The performance of DGANet was compared to three state-of-the-art algorithms with different genomic features. According to the results, GDANet outperformed the benchmark algorithms (AUROC = 92.76%, AUPRC = 92.49%), demonstrating a 3.36% AUROC and 4.05% accuracy improvement over the cutting-edge algorithms. We further proposed new genomic features that improved DGANet's predictive capability. Moreover, case studies on top-ranked candidates confirmed DGANet's ability to predict new ADRs.
He et al. (Mon,) studied this question.