Abstract
Drug-drug interactions (DDIs) are a critical component of drug safety surveillance. Laboratory studies aimed at detecting DDIs are typically difficult, expensive, and time-consuming; therefore, developing in-silico methods is critical. Machine learning-based approaches for DDI prediction have been developed; however, in many cases, their ability to achieve high accuracy relies on data only available towards the end of the molecule lifecycle. Here, we propose a simple yet effective similarity-based method for preclinical DDI prediction where only the chemical structure is available. We test the model on new, unseen drugs. To focus on the preclinical problem setting, we conducted a retrospective analysis and tested the models on drugs that were added to a later version of the DrugBank database. We extend an existing method, adjacency matrix factorization with propagation (AMFP), to support unseen molecules by applying a new lookup mechanism to the drugs’ chemical structure, lookup adjacency matrix factorization with propagation (LAMFP). We show that using an ensemble of different similarity measures improves the results. We also demonstrate that Chemprop, a message-passing neural network, can be used for DDI prediction. In computational experiments, LAMFP results in high accuracy, with an area under the receiver operating characteristic curve of 0.82 for interactions involving a new drug and an existing drug and for interactions involving only existing drugs. Moreover, LAMFP outperforms state-of-the-art, complex graph neural network DDI prediction methods.
Publisher
Public Library of Science (PLoS)
Reference37 articles.
1. Preventable Adverse Drug Reactions: A Focus on Drug Interactions; 2018. Available from: https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm110632.htm.
2. Suspected adverse drug events requiring emergency department visits or hospital admissions;R Raschetti;Eur J Clin Pharmacol,1999
3. National surveillance of emergency department visits for outpatient adverse drug events;DS Budnitz;JAMA,2006
4. A risky business: the detection of adverse drug reactions in clinical trials and post-marketing exercises;OP Corrigan;Social Science & Medicine,2002
5. A Comprehensive Review of Computational Methods for Drug-drug Interaction Detection;Y Qiu;IEEE/ACM Transactions on Computational Biology and Bioinformatics,2021