In-silico virtual prototyping multilevel modeling system for Cyborgs (CybSim) as a novel approach for current challenges in biosciencies

Abstract

There is a lack of Modeling and Simulation software systems in the bioscience arena that give both solutions compliant with current methodologies in drug discovery (pharmaceutic) and precision medicine (healthcare) fields, besides to support the addition of new biological mecha- nisms under a multilevel and multiformalism perspective, without penalize strongly the model sharing and reusing. A novel modeling and simulation software that tries to fill the previous gap has been designed (CybSim) and it is presented in this work. CybSim is a platform for multilevel modeling of physiological - cybernetic sys- tems, compliant but not limited to Physiologically based- , Pharmacokinetic and Pharmacodynamic (PBPK/PK/PD) methodologies. This capability is governed through the Physiological Scope setting value. The main physiologi- cal components are mechanistic. The underlying mechanisms may be changed during the model building thanks to the separation between mechanisms and physiological instances. This capability is based on a multilayer design. A preliminary version of CybSim has been implemented with OpenModelica (v1.14.1). A PBPK semiphysiological model published previously has been built as a case study to demonstrate the feasibility of CybSim. The accuracy of CybSim was verified during preliminary development phases. The two pointed out capabilities of CybSim demanded an object-oriented and acausal equation- based modeling language, able to support classes’ redeclaration, connectors’ causality, inner/outer scoping control and packages organization. These features are not supported by other modern acausal equation-based modeling languages like the EcosimPro language