Abstract
Various types of drug toxicity can halt the development of a drug. Because drugs are xenobiotics, they inherently have the potential to cause injury. Clarifying the mechanisms of toxicity to evaluate and manage drug safety during drug development is extremely important. However, toxicity mechanisms, especially hepatotoxic mechanisms, are very complex. The significant exposure of liver cells to drugs can cause dysfunction, cell injury, and organ failure in the liver. To clarify potential risks in drug safety management, it is necessary to systematize knowledge from a consistent viewpoint. In this study, we adopt an ontological approach. Ontology provides a controlled vocabulary for sharing and reusing of various data with a computer-friendly manner. We focus on toxic processes, especially hepatotoxic processes, and construct the toxic process ontology (TXPO). The TXPO systematizes knowledge concerning hepatotoxic courses with consistency and no ambiguity. In our application study, we developed a toxic process interpretable knowledge system (TOXPILOT) to bridge the gaps between basic science and medicine for drug safety management. Using semantic web technology, TOXPILOT supports the interpretation of toxicity mechanisms and provides visualizations of toxic courses with useful information based on ontology. Our system will contribute to various applications for drug safety evaluation and management.