JigCell

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

Abstract JigCell is a suite of ‘cell cycle modeling’ tools. It is also an effort to develop and maintain an ‘open source modeling’ environment for computational biology.

JigCell's goal is to support building and testing models for studying complex ‘biochemical regulatory’ systems in general, and the cell cycle control system in particular.

JigCell currently includes a 1) Model builder, 2) Run manager, 3) Comparator, and 4) Automatic parameter estimator.

The manufacturers hope to soon add a numerical bifurcation analysis package.

1) JigCell Model Builder --

The JigCell Model Builder (JCMB) aides the modeler in defining a system to be modeled using Systems Biology Markup Language (SBML). JCMB uses a spreadsheet interface, allowing a large amount of data to be displayed in an organized manner.

In addition to allowing the modeler to define chemical species, equations, and relationships, JCMB also provides the ability to define events that occur when a user-defined condition is met.

The models created with JCMB can be used in conjunction with the other JigCell tools to simulate the behavior of the model, and to evaluate the ability of the model to match the phenomena the model is meant to represent.

The JCMB allows the user to define a 'regulatory network' model using a spreadsheet interface. The JCMB provides a number of functionalities for both a first-time user and an expert modeler.

The first of these is the ability to define all the necessary components of a regulatory network model. JCMB allows the user to specify the reaction equations, functions, rate laws, and conservation relations that define a complete model.

In addition, JCMB also allows the modeler to specify units and events. An event, such as cellular division, can be defined by specifying a condition that must be met to trigger the event, and the changes that result due to the event.

A major goal of JCMB is to minimize the time and errors associated with translating a 'wiring diagram' for a regulatory network to a set of equations. JCMB accomplishes this through its spreadsheet interface.

As the user enters reaction equations, rate laws, and functions into their respective spreadsheets, several other spreadsheets are updated to track the species, parameters, equations [Ordinary Differential Equations (ODEs) and rule equations], and conservation relations associated with the model.

After the user has finished defining a model using JCMB, this model can be used with the other JigCell tools to simulate the response of the model to given conditions.

The JigCell Model Builder uses SBML Level 2 to define a model based on the data the user provides.

There are 10 different spreadsheets for model data; each spreadsheet is associated with a particular tab. There are eight (8) tabs for the different SBML components in a model (reactions, functions, rules, compartments, species, parameters, units and events).

There is one (1) tab for the Conservation Relations that exist in a model, and one (1) tab for the equations, both ODEs and rule equations.

2) JigCell Run Manager --

The JigCell Run Manager (JCRM) allows a user to specify a set of specifications for simulation runs using a spreadsheet interface. Each row of the spreadsheet describes the information necessary for a single simulation run.

JCRM serves two (2) chief purposes. The first is to organize related simulation runs, allowing the user to run and view the results of either the entire ensemble or of a single simulation. The second is to provide the specifications needed to run a simulation that matches a particular experiment.

This specification allows for another program such as the JigCell Comparator (see below...) to generate an assessment of how well experimental data matches simulation output.

To specify a simulation run, the user must provide a model, a parameter set, an initial condition set, and a simulator parameter set. These are all specified using a spreadsheet interface. These sets are called 'basal settings' and the three (3) types are parameter, initial condition, and simulator.

• a) Basal ‘parameter sets’ are initially derived from the parameters of an existing model. The user may then use an editor to derive new parameter sets from these and any subsequently derived sets.
• b) Basal ‘initial condition’ sets are initially derived from the 'initial conditions' of an existing model. The user may then use an editor to derive new initial condition sets from these and any subsequently derived sets.
• c) Basal ‘simulator parameter’ sets are initially discovered through Open Agent Architecture (OAA) calls to find available simulators. The user may then user an editor to derive new simulator parameter sets from these and any subsequently derived sets.

3) JigCell Comparator --

The Comparator is an integrated package of Java tools for performing a quantitative analysis on a collection of data sets. 'Core tools' for the system are focused around data entry, transformation, and analysis.

Additional tools can be created and linked with the Comparator. Domain users customize the Comparator by adding and removing tools.

JigCell is a suite for 'cell cycle modeling' that includes the Comparator.

The 'cellcycle module' is the collection of Comparator tools used by JigCell.

This module customizes entry of experimental data, supports dynamic data collection from models using the JigCell Model Builder and Run Manager, and performs ‘objective-based comparisons’.

4) JigCell Automatic parameter estimator --

Parameter Estimation (both in terms of allowing the user to search for good parameter values to a model by hand and allowing the computer to perform automated searches for good parameter values) is a major focus of the JigCell project.

The manufacturers have done extensive work toward building tools to support both user-based and automated parameter estimation. However, at this time the parameter estimation tools are Not integrated with the other components of the JigCell system.

A parameter estimator takes a biological model, experimental data, and the relationship between the model and data.

Using this information the parameter estimator uses numerical tools to vary the parameters to the model looking for the parameters that best fit the experimental data.

The manufacturer’s most current parameter estimation software is PET (Parameter Estimation Toolkit). PET is a graphical user interface (GUI) for discovering rate constants, of molecular network models, that fit experimental data.

It is designed for use by ‘theoretical biologists’ to build ‘regulatory network’ models and compare the models to experimental results.

PET contains many features intended to ease and quicken the model building process. To do this PET:

• a) Provides a GUI for entering a mathematical model [using the JigCell Model Builder (see above...)];
• b) Stores multiple sets of parameters and initial conditions (basal sets);
• c) Provides means for users to define changes to the model parameters and initial conditions (called simulation definitions) to mimic experiments;
• d) Simulates models using one or more basal set and simulation definition;
• e) Estimates parameters using a global or local parameter search algorithm;
• f) Plots simulations and experimental data in a grid of plots for visual comparison; and
• g) Provides undo/redo functionality.

System Requirements

Contact manufacturer.

Manufacturer

• JigCell is a joint effort by members of the Departments of Biology and Computer Science at Virginia Tech.
• Virginia Polytechnic Institute and State University
• Blacksburg, VA 24061-0002
• Their goal is to advance the state of the art for modeling in Systems Biology.

Manufacturer Web Site JigCell

Price Free for use under the DARPA BioSPICE user license.

G6G Abstract Number 20471

G6G Manufacturer Number 104096