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Probabilistic model by Bayesian network for the prediction of antibody glycosylation in perfusion and fed-batch cell cultures
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Industrial Biotechnology. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Centre for Advanced BioProduction by Continuous Processing, AdBIOPRO.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Centre for Advanced BioProduction by Continuous Processing, AdBIOPRO. KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Decision and Control Systems (Automatic Control).
KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Decision and Control Systems (Automatic Control). KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Centres, Centre for Advanced BioProduction by Continuous Processing, AdBIOPRO.ORCID iD: 0000-0002-9368-3079
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2021 (English)In: Biotechnology and Bioengineering, ISSN 0006-3592, E-ISSN 1097-0290, Vol. 118, no 9, p. 3447-3459Article in journal (Refereed) Published
Abstract [en]

Glycosylation is a critical quality attribute of therapeutic monoclonal antibodies (mAbs). The glycan pattern can have a large impact on the immunological functions, serum half-life and stability. The medium components and cultivation parameters are known to potentially influence the glycosylation profile. Mathematical modelling provides a strategy for rational design and control of the upstream bioprocess. However, the kinetic models usually contain a very large number of unknown parameters, which limit their practical applications. In this article, we consider the metabolic network of N-linked glycosylation as a Bayesian network (BN) and calculate the fluxes of the glycosylation process as joint probability using the culture parameters as inputs. The modelling approach is validated with data of different Chinese hamster ovary cell cultures in pseudo perfusion, perfusion, and fed batch cultures, all showing very good predictive capacities. In cases where a large number of cultivation parameters is available, it is shown here that principal components analysis can efficiently be employed for a dimension reduction of the inputs compared to Pearson correlation analysis and feature importance by decision tree. The present study demonstrates that BN model can be a powerful tool in upstream process and medium development for glycoprotein productions. 

Place, publisher, year, edition, pages
John Wiley and Sons Inc , 2021. Vol. 118, no 9, p. 3447-3459
Keywords [en]
Bayesian network, Chinese hamster ovary cells, glycosylation, mathematical modelling, monoclonal antibodies, Batch cell culture, Bayesian networks, Correlation methods, Decision trees, Immunological functions, N-linked glycosylation, Pearson correlation analysis, Predictive capacity, Principal components analysis, Probabilistic modeling, Therapeutic monoclonal antibodies, glycan, glycoprotein, monoclonal antibody, animal cell, Article, bioprocess, cell count, CHO cell line, controlled study, correlation analysis, decision tree, dimensionality reduction, drug manufacture, fed batch culture, female, gene expression, in vitro study, nonhuman, ovary cell culture, perfusion, principal component analysis, probability, uncertainty
National Category
Bioprocess Technology
Identifiers
URN: urn:nbn:se:kth:diva-308866DOI: 10.1002/bit.27769ISI: 000646323800001PubMedID: 33788254Scopus ID: 2-s2.0-85104130056OAI: oai:DiVA.org:kth-308866DiVA, id: diva2:1639340
Note

QC 20220221

Available from: 2022-02-21 Created: 2022-02-21 Last updated: 2022-06-25Bibliographically approved

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Zhang, LiangWang, MingliangHjalmarsson, HåkanChotteau, Véronique

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Zhang, LiangWang, MingliangHjalmarsson, HåkanChotteau, Véronique
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Industrial BiotechnologyCentre for Advanced BioProduction by Continuous Processing, AdBIOPRODecision and Control Systems (Automatic Control)
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Biotechnology and Bioengineering
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