Pathway Modeling - How To Introduce A Foreign Gene?

Question

[Heinz]

hello all,

Since im a newbie in bioinformatics this might be a noob question :)

I started using COPASI few weeks ago to do a simple metabolic pathway modeling to predic the production of desired metabolites using flux balance analysis (constrain, gene knockout, etc). Im using the experimental data of E. coli in SBML format. My question is how should i introduced a foreign gene that is not available in E coli into my model? for example gene from other species like bacillus subtilis etc...

Second, does anyone knows any R package that can be use form simulation like COPASI?

Regards

[Michael Schubert]

Copasi does not have R bindings, only Java, Python and C++. Also, I'm not sure if it supports FBA yet.

[Michael]

Michael, you are right, afaik COPASI doesn't support FBA

[Michael]

Heinz, a question to you: if COPASI doesn't support FBA, what kind of analysis did you really do, and how does this relate to what you really want to do?

[Heinz]

Thanks for the pointers. Im not actually running FBA in COPASI, I use the COBRA toolbox then create a model in which I composed in SBML and then run into COPASI to analyze the behavior of my model. Now what Im trying todo is, I wanna introduced set of foreign genes into the model and then analyze the behavior again.

Answer 1

[Michael]

In my understanding advantage of FBA is that you do not need extensive knowledge about the protein (e.g. Kinetic constants). What you need to know is certainly where the new enzyme would be placed in your network graph: that means, you need to know substrate and product of the reaction the enzyme catalyzes, and to be able to place this reaction in your existing model without creating a gap. In addition you need to define constraints for the flux rates through this enzyme. You can take the SBML file you have and edit it using CellDesigner, your file should be already FBA ready, that means it will contain constraints already. Then you can simply add an enzyme node for the new gene in the correct position. Using copy-paste that should be fairly simple, given you know where your node has to be placed. Also this article might be helpful: http://www.ncbi.nlm.nih.gov/pubmed/20057383

Edit: As Michael Schubert mentions FBA is not supported in COPASI, but maybe openCOBRA which is a Matlab library is suitable for you (Nature Protocols article). Or try FASIMU as a stand-alone application.

Answer 2

[martin.kavscek]

I think that the simplest way is to manualy type in the reaction which is catalysed with you desired protein. I use notepad++ just copy-paste the previous gene, properly annotate it (very important) and add a reactants and products in the right stochiometry. It is good that you can also add your own comments (date of introduction, the publications about the gene,...). In my opinion it is faster and more transparent way that doing it in some program.

Martin