Synergising stoichiometric modelling with artificial neural networks to predict antibody glycosylation patterns in Chinese hamster ovary cells
File(s)Stoichiometric-ANN hybrid model_R1 Final.docx (2 MB)
Accepted version
Author(s)
Antonakoudis, Athanasios
Strain, Benjamin
Barbosa, Rodrigo
Jimenez del Val, Ioscani
Kontoravdi, Kleio
Type
Journal Article
Abstract
In-process quality control of biotherapeutics, such as monoclonal antibodies, requires computationally efficient process models that use readily measured process variables to compute product quality. Existing kinetic cell culture models can effectively describe the underlying mechanisms but require considerable development and parameterisation effort. Stoichiometric models, on the other hand, provide a generic, parameter-free means for describing metabolic behaviour but do not extend to product quality prediction. We have overcome this limitation by integrating a stoichiometric model of Chinese hamster ovary (CHO) cell metabolism with an artificial neural network that uses the fluxes of nucleotide sugar donor synthesis to compute the profile of Fc N-glycosylation, a critical quality attribute of antibody therapeutics. We demonstrate that this hybrid framework accurately computes glycan distribution profiles using a set of easy-to-obtain experimental data, thus providing a platform for process control applications.
Date Issued
2021-11
Date Acceptance
2021-07-31
Citation
Computers and Chemical Engineering, 2021, 154, pp.1-11
ISSN
0098-1354
Publisher
Elsevier
Start Page
1
End Page
11
Journal / Book Title
Computers and Chemical Engineering
Volume
154
Copyright Statement
© 2021 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
https://www.sciencedirect.com/science/article/pii/S0098135421002490?via%3Dihub
Subjects
Chemical Engineering
0904 Chemical Engineering
0913 Mechanical Engineering
Publication Status
Published
Article Number
107471
Date Publish Online
2021-08-01