Error propagation in constraint-based modeling of Chinese hamster ovary cells
| Autor: | Jürgen Zanghellini, David E. Ruckerbauer, Dmytro Iurashev, Gunda Koellensperger, Michael Melcher, Diana Széliová, Nicole Borth |
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| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
Accuracy and precision genome-scale metabolic modeling Biochemical Phenomena flux balance analysis CHO Cells exchange rates 01 natural sciences Applied Microbiology and Biotechnology Ensure (product) Cricetulus 010608 biotechnology Cricetinae Metabolic modeling Animals error propagation Mathematics Propagation of uncertainty Observational error Chinese hamster ovary cell 010401 analytical chemistry Biological Transport General Medicine 0104 chemical sciences Flux balance analysis Constraint (information theory) Batch Cell Culture Techniques Constraint based modeling Chinese hamster ovary cells Molecular Medicine Biological system |
| Zdroj: | Biotechnology journalREFERENCES. 16(4) |
| ISSN: | 1860-7314 |
| Popis: | BackgroundChinese hamster ovary (CHO) cells are the most popular mammalian cell factories for the production of glycosylated biopharmaceuticals. To further increase titer and productivity and ensure product quality, rational systems-level engineering strategies based on constraint-based metabolic modeling, such as flux balance analysis (FBA), have gained strong interest. However, the quality of FBA predictions depends on the accuracy of the experimental input data, especially on the exchange rates of extracellular metabolites. Yet it is not standard practice to devote sufficient attention to the accurate determination of these rates.ResultsIn this work we investigated to what degree the sampling frequency during a batch culture and the measurement errors of metabolite concentrations influence the accuracy of the calculated exchange rates and further, how this error then propagates into FBA predictions of growth rates. We determined that accurate measurements of essential amino acids with low uptake rates are crucial for the accuracy of FBA predictions, followed by a sufficient number of analysed time points.ConclusionsWe observed that the measured difference in growth rates of two cell lines can only be reliably predicted when both high measurement accuracy and sampling frequency are ensured. |
| Databáze: | OpenAIRE |
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