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

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).