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Team:Edinburgh/Software
From 2008.igem.org
[http://www.ehmn.bioinformatics.ed.ac.uk/igem/ MGEC: Modeling Genetically Engineered Circuits]
Contents |
Objective
Make the generating of models for engineered gene circuits easier for Biologist
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 modeling. For Biologists who has no experience on modeling, 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 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 researches and 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 with the regulated genes. We developed a database for E. coli promoters which includes information on: transcription factor binding to the promoter, cofactors or other signals which active or deactive 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 type in directly the name of the transcription factor 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. 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 are added, a model in SBML format can be generated by pressing the “Create Model” button.
Features
1. as a web tool, no download required, easy to use than complex software tools
2. 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.
3. generating models in SBML format which is supported by over one hundred software tools for model analysis
4. the users have options to generate models with different complexity for the same circuit (to be completed)
5. 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 building models based on previously published data. (to be completed)
Further improvements
1. currently only support one gene is regulated by one transcription factor through binding in the promoter region. Support for combination regulation will be added later.
2. the users still need other software tools for modelling analysis. We are developing a sister website called SBML toolsets which includes functions for SBML model editor, visualization, time course simulation, steady state analysis and 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
