Investigating Hypotheses through Discovery of Relevant Models of Epithelial Transport

Abstract

Scientists often utilize computational models to help understand experimental observations or to investigate hypotheses in ways that are not practically achievable experimentally. The first step in constructing such models is to discover existing models which can be reused to help in such an investigation. We are developing novel research tools to enable the discovery and exploration of computational models relevant to specific research questions or hypotheses. This can aid biologists and clinicians to test their clinical or experimental hypotheses from a given collection of disparate mechanisms and/or observations such as diseases, drug actions and clinical observations.Computational tools and standards have evolved over the years such as CellML to encode mathematical models of biological systems; SemGen to annotate models; and the Physiome Model Repository (PMR) to store these models and their comprehensive descriptions to ensure the deposited knowledge is persistent, identifiable, discoverable and sharable. Our long term goal is to develop a knowledge management system capable of constructing multi‐scale renal nephron models from information extracted from PMR to investigate transport phenomena in the kidney at the cellular and subcellular level and the impact on nephron function.We have used the SemGen tool to comprehensively annotate a preliminary cohort of renal epithelial transport models available in PMR to provide the initial knowledgebase for model discovery and exploration, and in particular, to extract a model suitable for testing specific clinical or experimental hypotheses. One use of such exploration is the identification of missing resource(s), which could be addressed via more accurate description of existing resources or the addition of new resource to the repository.Specifically, we present here a web‐based tool enabling scientists to discover and explore epithelial transport models that are relevant to their specific research questions. Biologists and clinicians can use this tool to discover models with specific transport proteins, solute species, genes, anatomical location, or other relevant information. The result of this discovery is a “recipe” describing the computational model that can be assembled to help the user investigate their hypothesis.Support or Funding InformationSupported by the MedTech Centre of Research ExcellenceThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.