Visual Programming for Modeling and Simulation of Biomolecular Regulatory Networks

Abstract

In this paper we introduce our new tool BIOSKETCHPAD that allows visual programming and modeling of biological regulatory networks. The tool allows biologists to create dynamic models of networks using a menu of icons, arrows, and pop-up menus, and translates the input model into CHARON, a modeling language for modular design of interacting multi-agent hybrid systems. Hybrid systems are systems that are characterized by continuous as well as discrete dynamics. Once a CHARON model of the underlying system is generated, we are able to exploit the various analysis capabilities of the CHARON toolkit, including simulation and reachability analysis. We illustrate the advantages of this approach using a case study concerning the regulation of bioluminescence in a marine bacterium. Comments

Computational Techniques for Analysis of Genetic Network Dynamics

“…To prove qualitative properties of such systems, which are biologically significant, we developed the Multi-Affine Rectangular Partition (MARP) algorithm and the Rapidly Exploring Random Forest of Trees (RRFT) algorithm, and illustrate their usefulness by using as a case study, the phenomenon of luminescence production in the marine bacterium V. fischeri. While the case study was deliberately chosen to enable a low-dimensional model to facilitate graphical illustration through plots, the techniques here are applicable to very high-dimensional systems [3]. Future work is being directed towards developing tools for formal analysis of larger classes of hybrid systems, which could capture more complicated biochemical phenomena, and developing control laws for species in the network that can be directly controlled from outside the cell.…”

“…This is illustrated by a case study, the phenomenon of luminescence production in the marine bacterium V. fischeri. While a low-dimensional case study was deliberately chosen to facilitate graphical illustration, the techniques here are applicable to very high-dimensional systems (Alur et al 2002a). Future work is being directed towards developing tools for formal analysis of larger classes of hybrid systems, which could capture more complicated biochemical phenomena, and developing control laws for species in the network that can be directly controlled from outside the cell.…”

“…Therefore, both types systems can be modelled as hybrid systems. Indeed there are several papers that use hybrid models for molecular and cellular networks [3,7,8,4,2,22,15]. In addition, many robotic systems consist of multi-agent teams, and therefore the interactions and messaging among the team members must be taken into account and many of the system properties are distributed spatially.…”

“…We also propose the use of hybrid system as the natural framework for giving a global description of a biological system described locally around operating points by simpler dynamics, which are easier to approach for analysis. Our own work using hybrid systems to model, simulate and perform preliminary analysis on low-dimensional genetic networks is given (Alur et al 2001(Alur et al , 2002a(Alur et al , 2002bBelta et al 2001;Belta, Habets, and Kumar 2002); other work includes Glass (1975) and de Jong et al (2003).…”

Discrete Event Multi-level Models for Systems Biology

“…In contrast to that, Hybrid Automata [66] move the distinction of phases into the focus of modeling. State transitions of Hybrid Automata are triggered by continuous processes that are responsible for describing the continuous behavior of a system while being in one phase and determining the time and situation when to leave a phase and enter another one [67,68,69]. The growing need to integrate discontinuous behavior into Systems Biology models is reflected in extending existing simulation systems, e.g.…”