SAPHIR: a collaborative multi‐scale, multi‐resolution Core Model Environment for the Physiome—with a prototype core model of blood pressure regulation and fluid homeostasis

Abstract

We present the current state of the SAPHIR project, a multi‐resolution core modeling environment (CME) in the spirit of the IUPS Physiome, with application to a prototype core model based on a modular implementation of the classic systems model by Guyton et al. (1972 Ann. Rev. Physiol. 34:13–44) and its extension by Ikeda et al. (1979 Annals Biomed. Engin. 7:135–166). This core model targets short‐ and long‐term regulation of blood pressure and homeostasis of body fluids and major solutes. The aim is to provide a collaborative modeling environment enabling plug‐and‐play construction of integrated systems models with lumped‐parameter sub‐models at the organ/tissue level yet also allowing focus on cell‐ or molecular‐level detailed models embedded in the larger core model. Thus, in silico exploration of gene‐to‐organ‐to‐organism scenarios is possible while keeping computation time manageable. The CME is built on the M2SL toolbox, a multi‐scale, multi‐resolution, multi‐mode open source package developed in C++ by one of us (AH). Associated with the CME is an ontology‐based database allowing exploration of the modules, parameter values, and equations.In parallel with the CME implementation of the core model, we also present stand‐alone implementations in Berkeley Madonna (Ikeda model) and Simulink (Guyton model).