Adverse drug events constitute a major challenge for the success of clinical trials. Several computational strategies have been suggested to estimate the risk of adverse drug events in preclinical drug development. While these approaches have demonstrated high utility in practice, they are at the same time limited to specific information sources. Thus, many current computational approaches neglect a wealth of information which results from the integration of different data sources, such as biological protein function, gene expression, chemical compound structure, cell-based imaging and others. In this work we propose an integrative and explainable multi-modal Graph Machine Learning approach (MultiGML), which fuses knowledge graphs with multiple further data modalities to predict drug related adverse events and general drug target-phenotype associations. MultiGML demonstrates excellent prediction performance compared to alternative algorithms, including various traditional knowledge graph embedding techniques. MultiGML distinguishes itself from alternative techniques by providing in-depth explanations of model predictions, which point towards biological mechanisms associated with predictions of an adverse drug event. Hence, MultiGML could be a versatile tool to support decision making in preclinical drug development.
Keywords: Adverse event; Graph attention network; Graph convolutional network; Graph neural network; Knowledge graph; Machine learning.
© 2023 The Authors. Published by Elsevier Ltd.