Development, Integration and Simulation of Multiscale Mathematical Models of Physiological Processes: A Software Engineering Perspective

With the emergence of systems biology, modeling of physiological models started to adopt more integrative approaches instead of reductionist methods. In order to understand the complex system, which is human body, multiscale physiological models must be integrated and analyzed as a whole. However modeling and simulation of multiscale physiological processes deal with the challenges such as high coupling within and among scales. In order to deal with such challenges in a systematic way, there is a significant need for information technology solutions together with related analytical and computational tools that will facilitate integration of models and simulations of complex biological systems.;The idea of functional modularity and structural modularity presented in this thesis helps to cope with the highly complex and coupled nature of the physiological processes in the software level. Functional modularity is proposed through the use of information flow, which aims to separate the information and the flow of information in physiological processes. Ontology based design approaches are suggested for representing the anatomical and structural information of physiological processes, in order to achieve structural modularity.;In this thesis, we also present a software framework which is built on the principles of structural and functional modularity. Physiological Model Simulation, Integration and Modeling Framework (Phy-SIM) is an information technology framework to facilitate development, integration and simulation of large-scale highly-integrated models of human physiology.;Ultimate aim of Phy-SIM is to enhance the physiological model development processes; but more importantly to accelerate the development, analysis and testing of integration approaches for multiscale and multilevel physiological models.