Thermodynamically infeasible cycles (TICs)

[Subasree S]

Hello all,

How to identify and remove thermodynamically infeasible cycles (TICs) in context-specific genome-scale models? Do they interfere with the flux distribution to a large extent? 

If removing them makes the models infeasible, what alternative methods of model analysis can be followed in place of FBA or FVA?

[Ronan M.T. Fleming]

Hi Subasree,

there is confusion about this in the literature. A stoichiometrically
balanced cycle (e.g. A <-> B <-> C <-> A) is not a problem in a
network, unless one uses a flux prediction method that is not
guaranteed to remove thermodyamically infeasible flux around any
stoichiometrically balanced cycle (e.g. A -> B -> C -> A, or A <- B <-
C <- A). It is the wrong approach to remove stoichiometrically
balanced cycles from a network. As such "thermodynamically infeasible
cycles" is an ambiguous term that is not appropriate as it seems to
imply that it is each stoichiometrically balanced cycle is a problem
(it is not) rather than the method use to predict flux (which can be a
problem). There are other options, but in the cobra toolbox, the Cycle
Free Flux (https://academic.oup.com/bioinformatics/article/31/13/2159/195895)
algorithm has been implemented. You could try that.

Regards,

Ronan

https://github.com/opencobra/cobratoolbox/blob/master/src/analysis/thermo/thermoFBA/cycleFreeFlux.m

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--
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Mr. Ronan MT Fleming B.V.M.S. Dip. Math. Ph.D.
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Associate Professor,
School of Medicine,
National University of Ireland, Galway.
&
Assistant Professor,
Division of Systems Biomedicine and Pharmacology,
Leiden Academic Centre for Drug Research,
Faculty of Science,
Leiden University.
https://www.universiteitleiden.nl/en/staffmembers/ronan-fleming
&
H2020 Project Coordinator,
Systems Medicine of Mitochondrial Parkinson’s Disease,
http://sysmedpd.eu
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