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ArcDFI: Attention Regularization guided by CYP450 Interactions for Predicting Drug-Food Interactions

Gim, M.; Kang, J.; Park, D.; Jeon, M.

2025-04-15 pharmacology and toxicology
10.1101/2025.04.09.647981 bioRxiv
Show abstract

CYP450 isoenzymes are known to be deeply involved in the formation of drug-food interactions (DFI). Previously introduced computational approaches for predicting DFIs do not take drug-CYP450 interactions (DCI) into account and have limited generalizability in handling compounds unseen during model training. We introduce ArcDFI, a model that utilizes attention regularization guided by CYP450 interactions to predict drug-food interactions. Experimental results demonstrate ArcDFIs ability to predict DFIs when given unseen food or drug compounds as input. Analysis of its attention mechanism provides insight into its current understanding of DCI and how they are related to its DFI predictions. To the best of our knowledge, ArcDFI is the first DFI prediction model that incorporates the concept of DCI, resulting in improved predictive generalizability and model explainability. ArcDFI is available at https://github.com/KU-MedAI/ArcDFI

Published in PLOS Computational Biology (predicted rank #5) · training set

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