Epithelial Modelling Platform: A Tool for Investigating Hypothesis through Discovery and Assembly of Computational Models of Epithelial Transport

Abstract

Scientists often leverage computational models of biological systems to investigate hypotheses which are difficult or prohibitively expensive to achieve experimentally. Such investigations are best achieved by utilizing suitable computational models, reusing existing validated models where possible and creating novel models consistently as needed. This requires tools which enable the discovery and exploration of existing models matched with assistance in constructing and testing new models. Enabling scientists or clinicians to use such a tool by describing their requirements in a manner familiar to themselves greatly improves the accessibility of the tool. We have developed a web-based tool, the Epithelial Modelling Platform, for scientists and clinicians to discover relevant models and then assemble these into a novel model customized for investigating their hypotheses. While our tool specifically focuses on epithelial transport, by utilizing relevant community standards and publicly accessible knowledge repositories, it is extensible to other areas of application. The platform abstracts underlying mathematics of the computational models and provides a visual environment which mimics biological phenomena of an epithelial cell. Beyond the mathematical models, we have implemented a feature to discover existing simulation experiments which match the features of the novel models users create. By executing these simulation experiments with the novel models and comparing to previous model predictions and/or experimental or clinical observations we are able to provide the user with some measure of verification that their model matches, or doesn't match, existing knowledge captured in the various repositories utilized. Support or Funding Information Supported by the Medical Technologies Center of Research Excellence (MedTech CoRE), the Aotearoa Foundation, and the Auckland Bioengineering Institute Model discovery interface to search for models in the Physiome Model Repository (PMR) which are relevant to the query “flux of sodium”. By querying the biological knowledge stored in PMR the Epithelial Modelling Paltform retrieves components from the weinstein, mackenzie, and chang fujita models. Illustrating a similarity between weinstein and mackenzie model. In this case both models have similar compartment labeled with a unique color. An instance of the Epithelial Modelling Platform. It consists of five compartments and three membranes. Biological processes have been represented with various shapes: fluxes with circles; channels with polygons; and diffusive fluxes with a text, a line, and an arrow. On the right, check boxes have been generated for the visualized shapes on the membranes to allow the user to drag and drop. Concentration of the biological description of CellML variables float in the respective compartments. A suggestion window based on the biological description in the Physiome Model Repository when a circle, represented as flux of Na+ in the weinstein model, is moved from apical to basolateral membrane. A model verification instance for testing components of an assembled epithelial model reproduce the same simulation experiment. A model verification instance for testing components of an assembled epithelial model reproduce the same simulation experiment. A spider chart to find similarity of models with respect to an assembled epithelial model. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.