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

Abstract xCellerator (also called xlr8r) is a Mathematica based package designed to aide 'biological modeling' via the automated conversion of chemical reactions into Ordinary Differential Equations (ODEs) and their subsequent solution via numerical integration.

xCellerator is really a family of computer programs. Components include:

1) xlr8r - Reaction translation to ODE and numerical solution. The reaction syntax is backwards compatible with Cellerator (see below...) but is more general.

2) Cellzilla - Simulation of a Cellerator reaction network on a two- dimensional template. Cellzilla2D performs xCellerator simulations on two-dimensional tissue objects. Each cell is treated as a separate polygonal compartment.

The tissue object itself consists of three (3) parts: a list of vertex coordinates; a list of edges, composed of integer pairs of vertex numbers; and a list of cells consisting of integer lists of edge numbers. Tissues may be defined externally by the user, or one of a collection of predefined templates may be used.

3) SSA - Stochastic simulation using the Gillespie's stochastic simulation algorithm. SSA is a Mathematica package that implements Dan Gillespie's Stochastic Simulation Algorithm for biochemical simulations.

The input format is compatible with xCellerator reaction schema, but the package can be used independently of xCellerator. Only unimolecular and bimolecular mass action reactions are considered.

4) XSSA - extended SSA algorithm for stochastic simulation of most Cellerator reactions (Not just mass action) - [in development...].

5) CelleratorML/CellzillaML - an XML-based text file format for saving Cellerator and Cellzilla models. CelleratorML provides a way of storing Cellerator models, including initial conditions and parameter values, as ASCII text files, using XML.

CellzillaML is an extension of CelleratorML that allows one to store Cellzilla models, including cell center or tissue description parameters. All Cellerator reactions are represented in MathML. The entire MathML language is allowed, and in fact, is required, to represent Mathematica expressions.

Cellerator identifiers that contain characters in Mathematica's extended character set (ISO8559-1) are represented by their ASCII escape codes.

6) Systems Biology Markup Language (SBML) support through xlr8r2SBML and SBML2xlr8r plug-ins and MathSBML [(MathSBML is an open-source package for working with SBML models in Mathematica) - Mathematica is one of the world's most advanced global computation systems].

MathSBML provides facilities for reading SBML models, converting them to systems of ordinary differential equations for simulation and plotting in Mathematica, and translating the models to other formats. It supports both Level 1 and Level 2 SBML.

In addition there are a number of other programs that are compatible with xCellerator that can be used to extend its functionality. These include:

1) Sigmoid - an online database of 'Cellerator models' and a downloadable database manager, Sigmoid Model Explorer that can be used to query the database and perform simulations using xCellerator. Sigmoid is a database of cellular signaling pathways and models, used to marshall the major forms of data and knowledge required as input to cellular modeling software and also to organize the outputs.

Such cellular signaling and regulatory pathways are commonly hand- drawn in biological literature as an aid to intuitive understanding. Pathway databases can provide the same assistance in the context of attempts to achieve a quantitative understanding of ‘cellular processes’ by numerical simulation.

They can also serve as an aid to capturing and querying both 'expert knowledge' and heterogeneous data sets pertaining to pathways. Cell model databases are a subject of current research. Sigmoid works at the interface of these two areas.

To this end an object schema has been designed which incorporates reactions, reactants and models.

Reactions are further divided into elementary and composite biological processes, and reactants are divided into elementary and composite biological objects such as proteins (elementary in many but Not all situations) and protein complexes.

This coarse ontology is refined into a number of more detailed categories whose representation in common modeling software can be expected to be different.

2) kMech - a Cellerator mased enzyme mechanism language for the mathematical modeling of metabolic pathways.

This language, kMech, is a comprehensive collection of single and multiple substrate enzyme reactions and regulatory mechanisms that extends Cellerator function for the mathematical modeling of enzyme reactions.

Each mechanism has been codified to generate a set of elementary reactions that can be translated by Cellerator into ODEs solvable by Mathematica.

3) mPower - Voronoi, Delaunay, and power diagram computation in n- dimensions via QHULL and regtet. mPower is a Mathematica package.

4) Cambium - a mathematical process language for describing developmental models; the plug-in provides support for model conversion. (in development...)

5) Cellerator is a similar program that also converts reactions to ODEs, implemented by the same team of developers. It is Not as general as xlr8r, and less efficient. Cellerator has a more restrictive use and distribution license.

Cellerator is a Mathematica package that describes single and multi- cellular signal transduction networks (STN) with a compact optionally palette-driven, arrow based notation to represent biochemical reactions and transcriptional activation.

Multi- compartment systems are represented as graphs with STNs embedded in each node.

Interactions include mass- action, enzymatic, allosteric and connectionist models. Reactions are symbolically translated into differential equations and can be solved numerically to generate predictive time courses or output as systems of equations that can be read by other programs.

Cellerator is freely downloadable for academic/government/nonprofit users.

Note: xCellerator is similar to Cellerator but the implementation is fundamentaly different; it consequently runs 100 - 1000 times faster then Cellerator. It is currently in alpha-test stage and does Not have all features implemented.

When completed, it will be fully backwards compatible with Cellerator models, but will be more flexible and compatible with other programs.

It will also be fully integrated with MathSBML. Both Cellerator and xCellerator require Mathematica.

System Requirements

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Manufacturer Web Site xCellerator

Price Contact manufacturer.

G6G Abstract Number 20455

G6G Manufacturer Number 104082