AOP Network Box: An Integrative Framework for Bridging Adverse Outcome Pathways and Biological Networks

Adverse outcome pathways (AOPs) are biological mechanism-based models that connect chemical exposures to adverse outcomes (AOs) through molecular initiating events (MIEs) and key events (KEs). However, there is a notable gap in the available data on AOPs, such as chemicals associated with known AOPs and the associations between biological molecules and events. To address this challenge, we developed AOP Network Box─a multilayered network integrating chemical-protein interaction (CPI), protein-protein interaction (PPI), Gene Ontology (GO), and AOP network data. By leveraging this comprehensive integration, the AOP Network Box identifies AOPs associated with chemicals and facilitates the discovery of previously unknown relationships among chemicals, biological molecules, and events. This unified framework enables the discovery of previously unknown relationships among chemicals, biological molecules, and events, providing deeper insights into the mechanistic basis of chemical adverse outcomes. The web-based platform is freely available at https://aop-network-box.kaist.ac.kr.