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

Abstract

We address the need for modelling and predicting adverse outcomes in immunotoxicology to improve non-clinical assessments of immunomodulatory therapy safety and efficacy. 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 demonstrated with 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 via the MINERVA Platform for browsing, commenting and data visualisation (https://minerva.pages.uni.lu). Our work transforms a graphical illustration of an AOP into a digitally structured and standardised 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.