From physiological maps to disease ontology maps using a systems biology approach

Physiological Maps (PM) are comprehensive graphical representations of biological processes and interactions constructed using the standardized Systems Biology Graphical Notation. Using the CellDesigner graphical editor and the MINERVA platform, PMs facilitate the description of physiological processes in a mechanistic and modularized fashion. This approach allows for the representation of complex interactions and the seamless integration and organization of data from diverse sources. Inspired by the efforts of the Disease Maps community [1], we develop organ-specific PMs as part of the H2020 ONTOX project [2]: bile secretion & lipid metabolism (liver), nephron physiology (kidney), and neural tube closure & cognitive function development (developing brain). In ONTOX, PMs represent a foundation for the development of disease ontology maps that aim to integrate and annotate various types of data in addition to physiology. Ontology maps can be defined as mode-of-action frameworks that qualitatively and quantitatively integrate and structure relevant biological, toxicological, chemical and kinetic data from various sources. As an example, ontology maps aim to include an SBGN representation of AOP networks that will be fully integrated with the PM (biological layer) and will be usable in other systems biology workflows. These ontology maps allow the integration of other datasets such as omics data (overlays), chemical properties and kinetic information (tables). Ontology maps are being designed for 6 adverse outcomes: cholestasis and steatosis (liver), tubular necrosis and crystallopathy (kidney), neural tube closure and cognitive function defects (developing brain).The CellDesigner & MINERVA platforms enable seamless integration and annotation of different types of data and facilitate the creation of easy-to-interpret visual representations while ensuring machine readability and compatibility with other platforms used within ONTOX. PMs and ontology maps are products of collaborative efforts between domain experts and biocurators. They adhere to standardized guidelines for thorough annotation and documentation, ensuring alignment with the FAIR principles, which emphasize interoperability with various modeling tools and resources. Their evolution is anticipated to accelerate the creation of new approach methodologies for next-generation risk assessment, which can immensely benefit from the collaboration of the toxicology and systems biology communities.