Integrating multi-type features and knowledge graph for graded prediction of drug-induced liver injury in humans.

Drug-induced liver toxicity poses a threat to human health and remains a significant reason for drug withdrawal from the market. Therefore, early identification of drug-induced liver injury (DILI) during drug development is crucial. However, most studies on hepatotoxicity prediction are limited to single type of features or binary toxicity assessment. In this study, we propose a novel liver toxicity prediction model called MolFPKG-DILI (Molecular Graph, FingerPrint and Knowledge Graph-based DILI), which integrates multi-type compound features and knowledge graph for assessing DILI severity. Molecular fingerprints and molecular graphs capture different information of compounds, and models using individual features alone have shown limited performance. Our model incorporates an attention mechanism to effectively fuse the information from molecular fingerprints and molecular graphs. Furthermore, we leverage the relationship between drugs and other entities from the knowledge graph to achieve liver toxicity grading. Experimental results demonstrate that our proposed method exhibits highly competitive performance in both DILI/No-DILI and Most-DILI/Less-DILI classification. External validation conducted on an independent set of benchmark drugs yields satisfactory results, demonstrating the robustness of our approach. Additionally, we employ a series of interpretability methods to investigate the relationship between the different types of data utilized by the model and toxicity outcomes. These analyses highlight the interpretability of our method, providing valuable insights and support for drug toxicity evaluation.