A curated gene and biological system annotation of adverse outcome pathways related to human health

Adverse outcome pathways (AOPs) are emerging as a central framework in modern toxicology and other fields in biomedicine. They serve as an extension of pathway-based concepts by depicting biological mechanisms as causally linked sequences of key events (KEs) from a molecular initiating event (MIE) to an adverse outcome. AOPs guide the use and development of new approach methodologies (NAMs) aimed at reducing animal experimentation. While AOPs model the systemic mechanisms at various levels of biological organisation, toxicogenomics provides the means to study the molecular mechanisms of chemical exposures. Systematic integration of these two concepts would improve the application of AOP-based knowledge while also supporting the interpretation of complex omics data. Hence, we established this link through rigorous curation of molecular annotations for the KEs of human relevant AOPs. We further expanded and consolidated the annotations of the biological context of KEs. These curated annotations pave the way to embed AOPs in molecular data interpretation, facilitating the emergence of new knowledge in biomedicine.

Automated summary

Adverse outcome pathways (AOPs) serve as a central framework in modern toxicology and biomedicine, depicting biological mechanisms as causally linked sequences of key events (KEs). AOPs guide the development of new approaches and reduction in animal experimentation, and integrating them with toxicogenomics enables better interpretation of molecular mechanisms. Through rigorous curation, we have established a link between AOPs and molecular data interpretation, paving the way for new knowledge in biomedicine.