HELP! New to cobrapy

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Parsa Nayyara

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Jul 15, 2021, 3:21:31 AM7/15/21
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Hello, I'd like to do a flux balance analysis with cobra, however I currently have 0 experience in using python (though I feel I shouldn't need a deep understanding of it either in order to use COBRA?) - I wonder if anyone have any documents / tutorial videos which can help me learn all python basics I would need for COBRA?

Also, in what format should our model be to be analyzed using COBRA? 

Parsa Nayyara

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Jul 15, 2021, 3:25:47 AM7/15/21
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one more question though, would it also be possible to simulate new pathways that are not naturally found in the host organism?

dtm.van...@gmail.com

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Jul 21, 2021, 3:17:17 AM7/21/21
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Hi,

I would start with the cobrapy documentation for questions as which formats you can import and how cobrapy works, for a beginners course of python I found the free courses of datacamp are enough to get started and googling your specific problems or using stackoverflow and the python documentation will get you where needed.
About the question about new pathways: You can add your own reactions/metabolites to a model so construct whole pathways even if they are not in the model you use as a base.

Good luck,

Dennis

Parsa Nayyara

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Jul 31, 2021, 9:49:44 PM7/31/21
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Thanks for the reply! 

Is it possible to also test if certain compounds can be used as a carbon source? I have actually tried doing so by adding an exchange reaction for the compound I want (in my case an aromatic), as well as its catabolic pathway leading to the central metabolism. However, every time I tried to run FBA with biomass as objective, the model would only take up glucose and not the aromatic. But once I set the glucose uptake to 0.0, it still won't use the aromatic as carbon source and would return as 'infeasible'. 

Do you happen to have any suggestions or any idea on what the problem might be?

Dan Olson

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Aug 2, 2021, 9:27:05 AM8/2/21
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Sounds like your model can't use the specified aromatic compound as a carbon source. As far as I know, there is no automated way to troubleshoot this. Here are a couple of things I have done when trying to solve a similar problem:
1. Add exchange fluxes for redox (NAD, NADH, NADP, NADPH) and energy (ATP, ADP, AMP) to make sure those aren't limiting uptake
2. Make sure there is a pathway from your compound to central metabolism (i.e. if your compound gets degraded to acetate, set acetate as your objective)
3. Add an exchange flux for that central metabolite (i.e. acetate). In addition to the exchanges from step 1, you should be able to get growth.
4. Gradually eliminate your newly-added exchange fluxes to see where the problem is.

-Dan

Parsa Nayyara

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Aug 3, 2021, 8:02:06 AM8/3/21
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I tried doing those steps as you mentioned, turns out there was a by-product of one reaction that didn't have an exchange flux. The model works just fine now.  Thanks again for helping out! Also, is there any way I can predict whether the addition of the new catabolic pathway "burdens" the cell metabolically or not?
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