Using interactive platforms to encode, manage and explore immune-related adverse outcome pathways

Abstract

This work focuses on the need for modeling and predicting adverse outcomes in immunotoxicology to improve nonclinical assessments of the safety of immunomodulatory therapies. The integrated approach includes, first, the adverse outcome pathway concept established in the toxicology field, and, second, the systems medicine disease map approach for describing molecular mechanisms involved in a particular pathology. The proposed systems immunotoxicology workflow is illustrated with chimeric antigen receptor (CAR) T cell treatment as a use case. To this end, the linear adverse outcome pathway (AOP) is expanded into a molecular interaction model in standard systems biology formats. Then it is shown how knowledge related to immunotoxic events can be integrated, encoded, managed, and explored to benefit the research community. The map is accessible online at https://imsavar.elixir-luxembourg.org via the MINERVA Platform for browsing, commenting, and data visualization. Our work transforms a graphical illustration of an AOP into a digitally structured and standardized form, featuring precise and controlled vocabulary and supporting reproducible computational analyses. Because of annotations to source literature and databases, the map can be further expanded to match the evolving knowledge and research questions.

Keywords

• AOP
• adverse outcome pathway
• systems biology
• immunomodulatory therapies
• CAR T cells
• chimeric antigen receptor