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

Abstract AgentCell is an agent-based model of cellular biochemical processes and biological behavior. It uses agent-based technology to study the relationship between stochastic intracellular processes and behavior of individual cells.

As a test-bed for this approach the manufacturer uses 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.

In this first version of AgentCell, the manufacturer used only some of the features offered by the agent-based representation. Cells are the sole agents while cellular organelles (motors, receptors, etc.) are simple objects. These objects have No autonomy, and are controlled by the cell.

The first version provides several scripts to run simultaneously thousands of realizations of non-interacting single cells on parallel computers. The manufacturer used this feature to approximate the behavior of bacterial populations with averages over the realizations of independent non-interacting cells.

AgentCell Architecture --

The main packages and classes in this system are:

1) Models - This package contains classes that control different types of simulations. The main controller for the simulations is ChemotaxisModel.

2) World - This class defines the space in which the cells (agents) live. World contains a Collection of cells as well as an instance of the BoundaryConditions class, essentially a Collection of boundaries that can be either reflective or periodic.

For simplicity, reflective boundaries reflect oriented positions as if they were particles bouncing elastically against a wall.

3) Cells - The default attributes of a cell are position, orientation, volume and motionStepper. They are provided by the abstract class Cell. Each instance of the Cell class is an independent agent.

4) The ChemotaxisCell class extends Cell with attributes necessary to perform chemotaxis: Receptors, Network, Motor, Flagella.

a) Receptors - This class provides a method to read the concentration of ligand from the local environment.

b) Network - All biochemical networks use the Network interface. This interface declares methods to set and get the number of molecules in the networks.

It also declares a step method to advance the network in time. Network is implemented by the class Stochsim, a wrapper around the StochSim software package (see G6G Abstract Number 20468).

Stochsim uses the same input files as the original StochSim program to define the topology and reactions rates of the network. For the chemotaxis pathway, this is done in the ChemotaxisNetwork class.

New additional pathways require a separate set of Stochsim input files.

c) Motor - Bacterial motors rotate either clockwise or counter-clockwise. The abstract class Motor keeps track of the binary state (CW or CCW) of the effective motor and provides a method to switch from one state to the other.

It also declares an abstract step method to advance the state of the motor in time.

The abstract class ThresholdMotor extends Motor with a time step method that switches the motor state from CCW to CW, if a threshold condition is satisfied.

The threshold condition is defined in subclasses: AveragedCheYpThresholdMotor defines the threshold using the recent history of the intracellular level of CheY-P.

d) Flagella - Changes in the states of the motors do not always translate into changes in swimming behavior. The abstract class Flagella handles this discrepancy.

The current model allows two (2) possible states for the flagella: bundled when the flagella form a corkscrew bundle and apart when the flagella fly apart. The subclasses of Flagella, TetheredFlagellum and SwimmingFlagella, switch the state of the flagella according to the state of the motor.

5) Motion - This package controls the motion of a cell within the World.

Two interfaces, Motion and MotionStepper handle the cellular motion. Motion represents cell movements, like a run or a tumble. MotionStepper calls the step routines of the different types of movement.

For chemotaxis, Motion is implemented by the Run and Tumble classes. MotionStepper is implemented by the RunTumbleStepper class which is responsible for executing a Run or a Tumble step depending on the current state of the Motor.

6) Molecules - This package defines molecular types (Molecule), concentration (Concentration), copy numbers (CopyNumber), and concentration fields (ConcentrationField).

AgentCell Software --

The manufacturer built AgentCell using the agent-based Repast framework (see G6G Abstract Number 20434).

Repast is an agent-based framework similar to its predecessor Swarm (see G6G Abstract Number 20436) but differs in several important respects.

Owing to its implementation in Java, Repast is platform independent, web-compatible and allows integration across a variety of languages. All the capabilities of Repast are directly available within AgentCell.

In particular, Repast provides the software apparatus for creating, running, displaying and collecting data from an agent-based simulation.

It also has libraries for handling complex interactions between agents. The ChemotaxisModel class extends the SimpleModel class from Repast.

It is responsible for starting and terminating higher-level housekeeping tasks, such as I/O, random number generation, threaded process assignment, interfacing with the graphical user interface and scheduling.

In addition to Repast, AgentCell uses the Apache Log4J high performance Java-based results logging system, the National Center for Supercomputing Applications’ (NCSA) Hierarchical Data Format 5 (HDF5) data storage system and the Colt mathematics library among other tools.

These libraries provide AgentCell with useful functionalities, such as the ability to store results either in HDF5 or in comma separated value (CSV) format.

System Requirements

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Manufacturer Web Site AgentCell

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G6G Abstract Number 20437

G6G Manufacturer Number 104066