AgentCell (Digital E. Coli)

T. Emonet, C. Wickersham & P. Cluzel (Institute for Biophysical Dynamics, University of Chicago)
C. Macal, M. North (Center for Complex Adaptive Agent Systems Simulation, Argonne National Laboratory)
B. Gallagher (ASC Flash Center Visualization Group, University of Chicago)

This work is partially supported by joint research funding under H.28 of the U. S. Department of Energy Contract W-31-109-ENG- 38. It is an ongoing collaboration between P. Cluzel's lab (UofC) and CCAASS (Argonne National Laboratory)

Introduction

In recent years, single-cell biology has focused on the relationship between the stochastic nature of molecular interactions and variability of cellular behavior. To describe this relationship, it is necessary to develop new computational approaches at the single cell level.

We have developed AgentCell, a model using agent-based technology to study the relationship between stochastic intracellular processes and behavior of individual cells. As a test-bed for our approach we use bacterial chemotaxis, one of the best-characterized biological systems. In this model, each bacterium is an agent equipped with its own chemotaxis network, motors and flagella. Swimming cells are free to move in a 3D environment. Digital chemotaxis assays reproduce experimental data obtained from both single cells and bacterial populations.

(a) Chemotactic swimming cell exposed to a linear gradient of chemo-attractant (shaded background). When the motors rotate CCW (see main text) the flagella form a corkscrew bundle and the cell runs. When the motors rotate CW, the flagella bundle flies apart and the cell tumbles erratically. (b) Schematic diagram of the chemotactic pathway. Receptor complexes consist of three Tar receptor dimers (T), two CheW (W), and two CheA (A). The activity of aspartate (a) receptor complexes is modulated by methylation (m) and demethylation respectively catalyzed by CheR (R) and CheB (B). The autophosphorylation of CheA (A), a histidine kinase, is controlled by the activity of the receptors. CheA catalyzes the phosphorylation of the response regulator CheY (Y). When CheY is phosphorylated (Yp), it binds to the cytoplasmic domain of the bacterial motor and induces tumbles. Dephosphorylation of CheY-P (Yp) is catalyzed by the phosphatase CheZ (Z).

Results and animations

Software and bug fixes

AgentCell is now fully compatible with the latest version of StochSim (StochSim-1.6_core_2007JUL05.tar.gz NOT to be mixed up with the 1.6beta version of StochSim). Our changes to StochSim have now been merged into the main development trunck of StochSim. The latest version of StochSim on the sourceforge server is now fully compatible with this new version of AgentCell. StochSim is not distributed with AgentCell anymore. It is available on sourceforge. We still provide the StochSim file here for convenience. AgentCell uses parts of Repast as a layer to provide agent-based capabilities. Repast is distributed under a BSD license and is included in the AgentCell distribution. AgentCell is distributed under the GPL license. AgentCell includes Xerces XML software developed by the Apache Software Foundation (http://www.apache.org/). Please see the "licenses" directory for the licensing details of AgentCell and the software distributed with AgentCell.

AgentCell Version 2.0 (download) (README)

This new version of AgentCell can now handle many cells in the same VM. It is also fully compatible with the latest version of StochSim that can be found on sourceforge.

AgentCell Version 1.2 (download)

This version still uses version 1.4 of StochSim but with some important bug fixes:

AgentCell Version 1.0 (download)

Original version of AgentCell used in Bioinformatics 21, 2714-2721 (2005). Implementing the Network class with StochSim required the accessing of the internal time loop of StochSim in order to feed or extract information at the time intervals required by the agent-based simulation. For this purpose we modified StochSim to appropriately pause and then continue as required by Repast. This new version of StochSim eventually will become the main branch of the StochSim development tree (in version 1.4 of AgentCell)

Because of the use of global variables in StochSim 1.4, only one instance of StochSim 1.4.1 can be used in each Java VM. In practice we run many independent AgentCells on a cluster, one AgentCell per node (see explanations in the paper). Our goal however is to have cells interacting with each other. To that end Tom Shimizu and Michael North have modified StochSim 1.4.1, removing all global variables and therefore allowing many instances of the StochSim class within one AgentCell simulation. This new version of StochSim is currently being tested and will be released with the next version of AgentCell.

This version contains two important bugs that are fixed in version 1.2

Download

The code is available for download from SourceForge. To install download the distribution (zip file) from SourceForge, unpack and follow the instructions in the README file.

Getting involved

AgentCell is an open source project. Any contribution is welcome. To get involved, subscribe to the AgentCell-developer mailing list below.

Mailing lists

License

AgentCell is free software distributed under the GPL License. It includes other software such as (Repast, StochSim, ...). Licenses for each package can be found in the licenses directory within the distribution package. Repast is licensed under a BSD license. StochSim 1.4.1 (the modified 1.4 version) is included with AgentCell and is distributed under the LGPL license. AgentCell includes Xerces XML software developed by the Apache Software Foundation (http://www.apache.org/).