S2: Software platform supporting multilevel modeling

Software platform supporting multilevel modeling and simulations of physiological systems toward systems toxicology

Software platform supporting multilevel modeling, OpenTox Asia 2017

Yoshiyuki Asai


Yamaguchi University Graduate School of Medicine




The importance of systems biological approaches in toxicity assessments has been well recognized recently, where physiologically plausible mathematical models are used as powerful tools. Since such models are continually evolving in size and complexity for possible clinical and experimental applications, systematic support by software is also increasingly becoming important.

There are several pioneering efforts to develop technologies in that direction, such as SBML (Systems Biology Markup Language) and CellML among others, which are XML-based formats to describe models of biological and physiological systems. Software applications, such as CellDesigner for dealing with SBML models, OpenCell for simulations of models written in CellML, and others, have been also developed. The main purpose in developing these languages and applications is to establish common communication foundations, and to enhance the exchange of models among collaborators. Besides that, such languages are computer readable, which have potential to expand the modeling ability by cooperating with machine learning technologies, or AI technologies.

In this stream, we have developed a modeling platform, PhysioDesigner, with a model descriptive language PHML (Physiological Hierarchy Markup Language) which can cooperate with SBML, and has partial interoperability with CellML. PhysioDesigner equips an intuitive graphical user interface, allowing users to build models of physiological systems characterized by hierarchical structures. Besides developing models with mathematical expressions, time series data and morphometric data can be integrated into the models. Flint, a standalone simulator supporting PHML as well as SBML, has been developed concurrently with PhysioDesigner. As an extension of Flint, a cloud-based simulation system Flint K3 is publically available at flintk3.org.

In the talk, the software platform is introduced with a couple of simulations results obtained from models of cardiac cells, pancreatic beta cells and a physiologically based pharmacokinetics model of drug-drug interactions, written in PHML.