Validation-based model selection for 13C metabolic flux analysis with uncertain measurement errors
Fig 1
The basic steps in 13C MFA and the model selection problem.
(A) New substrates, containing 13C (dark circles) are fed to the cells. (B) These substrates are consumed and converted to end products in the cells, according to its biochemical reactions. (C) The labelled 13C molecules appear to various proportions in each of the mass isotopomers, and these proportions are summed up in these distribution bar charts for each detected metabolite. (D) The iterative modelling cycle in which a hypothesized model structure is fitted to MID data. The model fit is evaluated, usually with a χ2-test, and either rejected or not. If the model structure is rejected it is revised and evaluated again. If the model structure is not rejected it is used for flux determination. (E) The iterative model development in (D) results in a model selection problem. Different approaches for solving this model selection problem might result in different model structures being selected. This paper evaluates how the uncertainty in measurement data affects uncertainty in model selection.