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Cell culture process metabolomics together with multivariate data analysis tools opens new routes for bioprocess development and glycosylation prediction
Authors:Philipp Zürcher  Michael Sokolov  David Brühlmann  Raphael Ducommun  Matthieu Stettler  Jonathan Souquet  Martin Jordan  Hervé Broly  Massimo Morbidelli  Alessandro Butté
Affiliation:1. Department of Chemistry and Applied Biosciences, Institute of Chemical and Bioengineering, ETH Zürich, Switzerland;2. Merck Biopharma, Biotech Process Sciences, Corsier-sur-Vevey, Switzerland;3. Department of Chemistry and Applied Biosciences, Institute of Chemical and Bioengineering, ETH Zürich, Switzerland

DataHow AG, Zurich, Switzerland

Abstract:Multivariate latent variable methods have become a popular and versatile toolset to analyze bioprocess data in industry and academia. This work spans such applications from the evaluation of the role of the standard process variables and metabolites to the metabolomics level, that is, to the extensive number metabolic compounds detectable in the extracellular and intracellular domains. Given the substantial effort currently required for the measurement of the latter groups, a tailored methodology is presented that is capable of providing valuable process insights as well as predicting the glycosylation profile based on only four experiments measured over 12 cell culture days. An important result of the work is the possibility to accurately predict many of the glycan variables based on the information of three experiments. An additional finding is that such predictive models can be generated from the more accessible process and extracellular information only, that is, without including the more experimentally cumbersome intracellular data. With regards to the incorporation of omics data in the standard process analytics framework in the future, this works provides a comprehensive data analysis pathway which can efficiently support numerous bioprocessing tasks.
Keywords:CHO cell culture  glycosylation  metabolomics  multivariate analysis  partial least square regression
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