Journal Article

Predicting drug combination side effects based on a metapath-based heterogeneous graph neural network

Wang, Qi, Tian, Leixia, Yan, Guiying, Liu, Xiya, Zhou, Zhiheng, Zhang, Ming

2025

Overview

In recent years, combined drug screening has played a very important role in modern drug discovery. Generally, synergistic drug combinations are crucial in treatment for many diseases. However, the toxic side effects of drug combinations are probably increased with the increase of drugs numbers, so the accurate prediction of toxic side effects of drug combinations is equally important. In this paper, we built a Metapath-based Aggregated Embedding Model on Single Drug–Side Effect Heterogeneous Information Network (MAEM-SSHIN), which extracts feature from a heterogeneous information network of single drug side effects, and a Graph Convolutional Network on Combinatorial drugs and Side effect Heterogeneous Information Network (GCN-CSHIN), which transforms the complex task of predicting multiple side effects between drug pairs into the more manageable prediction of relationships between combinatorial drugs and individual side effects. MAEM-SSHIN and GCN-CSHIN provided a united novel framework for predicting potential side effects in combinatorial drug therapies. This integration enhances prediction accuracy, efficiency, and scalability. Our experimental results demonstrate that this combined framework outperforms existing methodologies in predicting side effects, and marks a significant advancement in pharmaceutical research.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Accuracy / Adverse and side effects / Algorithms / Artificial intelligence for drug design / Artificial neural networks / Bioinformatics / Biomedical and Life Sciences / Combinatorial analysis / Combinatorial drugs / Complications and side effects / Computational Biology - methods / Computational Biology/Bioinformatics / Computer Appl. in Life Sciences / Drug Combinations / Drug development / Drug Discovery - methods / Drug screening / Drug therapy / Drug therapy, Combination / Drug-Related Side Effects and Adverse Reactions / Drugs / Embedding / Frequency distribution / Graph convolutional network / Graph Neural Networks / Graphs / Heterogeneous information network / Humans / Knowledge representation / Life Sciences / Metapath / Microarrays / Neural networks / Neural Networks, Computer / Predictions / Proteins / Side effect prediction / Side effects