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Adaptive flux variability analysis of HEK cell cultures

par Abbate, Thomas;Dewasme, Laurent;Wouwer, Alain Vande;Bogaerts, Philippe
Référence Computers & chemical engineering, 133, 106633
Publication Publié, 2020-02-01

Article révisé par les pairs

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Résumé :

Measured external fluxes impose constraints to under-determined metabolic networks that narrow the internal flux intervals obtained using Flux Variability Analysis. Nevertheless, these constraints often lead to systems that do not admit a feasible solution. Measurement noise and data smoothing are among the sources of uncertainties that can cause system infeasibility. These constraints are classically released using interval representation of fluxes. This study investigates the use of Adaptive Flux Variability Analysis (AFVA), which allows determining a minimal coefficient of variation of the external fluxes along the time course of the experiment. Especially, AFVA is applied to a medium-size metabolic network and a rich dataset relative to HEK-293 cells cultured in batch, encompassing all 20 amino acids and less commonly measured metabolites, such as urea and pyruvate. AFVA appears as an effective tool for metabolic flux analysis. The impact of data-smoothing and the information provided by the cell growth are thoroughly analyzed.