HepatoToxicity Portal (HTP): an integrated database of drug-induced hepatotoxicity knowledgebase and graph neural network-based prediction model

Liver toxicity poses a critical challenge in drug development due to the liver's pivotal role in drug metabolism and detoxification. Accurately predicting liver toxicity is crucial but is hindered by scattered information sources, a lack of curation standards, and the heterogeneity of data perspectives. To address these challenges, we developed the HepatoToxicity Portal (HTP), which integrates an expert-curated knowledgebase (HTP-KB) and a state-of-the-art machine learning model for toxicity prediction (HTP-Pred). The HTP-KB consolidates hepatotoxicity data from nine major databases, carefully reviewed by hepatotoxicity experts and categorized into three levels: in vitro, in vivo, and clinical, using the Medical Dictionary for Regulatory Activities (MedDRA) terminology. The knowledgebase includes information on 8,306 chemicals. This curated dataset was used to build a hepatotoxicity prediction module by fine-tuning a GNN-based foundation model, which was pre-trained with approximately 10 million chemicals in the PubChem database. Our model demonstrated excellent performance, achieving an area under the ROC curve (AUROC) of 0.761, surpassing existing methods for hepatotoxicity prediction. The HTP is publicly accessible at https://kobic.re.kr/htp/ , offering both curated data and prediction services through an intuitive interface, thus effectively supporting drug development efforts.Scientific contributionsHTP-KB consolidates comprehensive curated information on liver toxicity gathered from nine sources. HTP-Pred utilizes advanced deep learning techniques, significantly enhancing predictive accuracy. Together, these tools provide valuable resources for researchers and practitioners in drug development, accessible through a user-friendly interface.