Unlocking liver physiology: comprehensive pathway maps for mechanistic understanding

In silico methods provide a resourceful toolbox for new approach methodologies (NAMs). They can revolutionize chemical safety assessment by offering more efficient and human-relevant alternatives to traditional animal testing. In this study, we introduce two Liver Physiological Maps (PMs); comprehensive and machine-readable graphical representations of the intricate mechanisms governing two major liver functions. These maps are designed to facilitate a deeper understanding of human liver function and its perturbations by chemicals. Built from manually curated literature, the Liver PMs standardize existing knowledge on liver lipid metabolism and bile acid biosynthesis and secretion. Available for online interactive visualization and exploration these maps adhere to the Findable, Accessible, Interoperable, and Reusable (FAIR) principles, ensuring easy and open access, interoperability, and reusability. They offer a holistic view of liver-specific pathways supporting the development of a more accurate and human-based strategy for next generation risk assessment of chemicals.