Cyto-Sim

Category Cross-Omics>Agent-Based Modeling/Simulation/Tools

Abstract Cyto-Sim is a stochastic simulator of membrane-enclosed hierarchies of biochemical processes, where the membranes comprise an inner, outer and integral layer.

The underlying model is based on formal language theory and has been shown to have decidable properties, allowing formal analysis in addition to simulation.

The simulator provides variable levels of abstraction via arbitrary chemical kinetics which link to ordinary differential equations (ODEs).

In addition to its compact native syntax, Cyto-Sim currently supports models described as Petri nets, can import all versions of Systems Biology Markup Language (SBML) and can export SBML and MATLAB m- files.

Simulator model is based on P systems --

The manufacturer's simulator model is based on P systems (a.k.a. Membrane Systems), a computational paradigm based on compartments, which draws its inspiration from biological cells: multi-sets of objects are enclosed in a nested hierarchy of compartments and acted upon by local rewriting rules.

This translates to: populations of molecules in a nested hierarchy of cellular compartments acted upon by local chemical reactions.

The manufacturer has extended the basic Membrane Systems model to include peripheral and integral membrane proteins and incorporate an efficient Monte Carlo algorithm to simulate the time evolution of the system.

The model includes standard, chemical rewriting rules and rules which allow the passage of objects between compartments, mediated by membrane objects (membrane proteins).

The manufacturer has previously shown that useful properties (e.g., reachability of configurations) of the general model are decidable, hence it is possible to export specific models and investigate them using model checking techniques [e.g. via SBML to PRISM (see below...)] or analyze them using the techniques of symbolic dynamics.

PRISM --

PRISM is a probabilistic model checker, a tool for formal modeling and analysis of systems which exhibit random or probabilistic behavior.

It supports three (3) types of probabilistic models: discrete-time Markov chains (DTMCs), continuous-time Markov chains (CTMCs) and Markov decision processes (MDPs), plus extensions of these models with costs and rewards.

PRISM has been used to analyze systems from a wide range of application domains, including communication and multimedia protocols, randomized distributed algorithms, security protocols, biological systems and many others.

Cyto-Sim's Default level of abstraction --

The manufacturer's default level of abstraction is chemistry: objects interact governed by stoichiometric rules at a rate defined by mass action kinetics.

A variable level of abstraction is facilitated by the use of arbitrary kinetic laws: objects are consumed and produced at rates defined by arbitrary functions of reactants.

This facility is a necessity to represent Michaelis-Menten enzyme kinetics, for example.

In general, complex behavior involving many reactions can be reduced to a single rule and an appropriate kinetic function.

This allows the manufacturer to model the diffusion of substances through ‘membranes’ without the computational burden of spatial simulation.

Cyto-Sim's Native language --

The simulator’s native language aims to be intuitive and uncluttered. Objects, rules and compartments are defined and then (a subset of) these are composed to create the final system to simulate.

In this way it is Not necessary to explicitly define rules and objects for each compartment, as is necessary, e.g. in SBML.

This compositional approach leads to a compact description of the model.

Petri nets are a popular graphical representation of logical flows, which have been successfully applied to biology. Hence, in addition to the native rule syntax, Cyto-Sim supports rule definitions in the form of Petri net incidence matrices.

By default, the transitions adopt mass action kinetics, i.e. the rate of the transition is proportional to a constant multiplied by the product of the numbers of tokens in the incoming places.

Other Petri net dynamics are also possible by explicitly defining appropriate kinetic laws, in the same manner as the native syntax.

Cyto-Sim's Core Simulation engine --

The core simulation engine is an efficient implementation of a Markov chain Monte Carlo algorithm, using ideas from Gillespie [Gillespie DT; Exact stochastic simulation of coupled chemical reactions. J. Phys. Chem (1977) 81:2340–2361].

Performance is optimized for mass action chemical kinetics; however the algorithm also supports chemical reactions with arbitrary kinetic laws based on functions of the reactants.

This is achieved in an efficient way, using compiler technology and a virtual machine, in such a way as Not to adversely affect the performance of the default kinetics.

System Requirements

Cyto-Sim is available either as an applet or a stand-alone Java program via the manufacturer's web page.

Manufacturer

Manufacturer Web Site Cyto-Sim

Price Contact manufacturer.

G6G Abstract Number 20593

G6G Manufacturer Number 104196