A simplified similarity-based approach for drug-drug interaction prediction

Guy Shtar, Adir Solomon, Eyal Mazuz, Lior Rokach, Bracha Shapira

Research output: Contribution to journalArticlepeer-review


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 Drug- Bank 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.

Original languageEnglish
Article numbere0293629
JournalPLoS ONE
Issue number11 November
StatePublished - Nov 2023

Bibliographical note

Publisher Copyright:
© 2023 Shtar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


  • Databases, Factual
  • Drug Interactions
  • Machine Learning
  • Neural Networks, Computer
  • Retrospective Studies


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