Team:Edinburgh/Software

MGEC: Modeling Genetically Engineered Circuits

Objective
To make the generating of models for engineered gene circuits easier for biologists.

Background
Many software tools (such as Copasi and SimBiology) are available for simulation and analysis of biological circuits using mathematical models. However, most tools require the users to convert a designed circuit into a set of reaction equations for modelling. For a biologist who has no experience in modelling, this process is not straightforward. Therefore we developed a web tool called MGEC (Modeling Genetically Engineered Circuits) to address this issue. Through MGEC, one only needs to tell which genes and promoters are assembled in order to form their gene circuit - a preliminary model in SBML format will be automatically generated for the circuit. This model can then be analyzed in other software such as Copasi for further improvement.

Design of MGEC
Database

A key technology used for engineering gene circuit in Synthetic Biology research and the iGEM competition is the recombination of genes with different promoters. Therefore the focus of MGEC is also on the promoters which link the signal, transcription factor (TF) with the regulated genes. We developed a database for E. coli promoters which includes information on: TF binding to the promoter, cofactors or other signals which activate or deactivate the TF, corresponding MIT registry ID (if any) or other database ID, kinetic information from published papers about the promoter, etc.

Web Interface

A web interface was designed which allows the users to type in the promoter name and the name of the gene assembled with the promoter. Many promoter-gene pairs can be input one by one for generating a complex circuit. Alternatively, if a promoter is not in the database, the users can directly enter the name of the TF binding to the promoter.

Model generation

For each promoter-gene pair, two reaction equations will be generated for the model (In the future version, users will have options to generate models with different sets of reactions). One is for the production of the gene product where the corresponding TF is the modifier. Another is for the degradation of the gene product. The Hill equation is used for the kinetic equation of the production process and mass action kinetics for the degradation. Once all the promoter-gene pairs forming the circuit have been added, a model in SBML format can be generated by pressing the “Create Model” button.

Features
1.	As a web tool, no download is required.

2.     Easier to use than complex software tools.

3.	The users can directly type in the MIT registry parts IDs used in their circuit design to build a model. This is especially useful for the iGEM teams.

4.	Generating models in SBML format which is supported by over one hundred software tools for model analysis.

5.	The users have options to generate models with different levels of complexity for the same circuit. (to be completed)

6.	Supported by a background database which includes literature based kinetic information (such as kinetic equations and parameter values) for the regulatory parts, thus allowing users to build models based on previously published data. (to be completed)



Further improvements
1.	Currently only supports genes being regulated by one transcription factor through binding in the promoter region. Support for combinatory regulation will be added later.

2.	The users still need other software tools for modeling analysis. We are developing a sister website called SBML toolsets which will include functions of a SBML model editor, visualization, time course simulation, steady state analysis, parameter sensitivity analysis, etc. Through these two site, the users will be able to do all the model related analysis on line.

3.	Support for metabolic pathways and signal transduction pathway models will also be added.

Have a try: the software MGEC