Novel column generation-based optimization approach for poly-pathway kinetic model applied to CHO cell culture
Mathematical modelling can provide precious tools for bioprocess simulation, prediction, control and optimization of mammalian cell-based cultures. In this paper we present a novel method to generate kinetic models of such cultures, rendering complex metabolic networks in a poly-pathway kinetic mode...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | Metabolic Engineering Communications |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214030117300263 |
| _version_ | 1818329792853835776 |
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| author | Erika Hagrot Hildur Æsa Oddsdóttir Meeri Mäkinen Anders Forsgren Véronique Chotteau |
| author_facet | Erika Hagrot Hildur Æsa Oddsdóttir Meeri Mäkinen Anders Forsgren Véronique Chotteau |
| author_sort | Erika Hagrot |
| collection | DOAJ |
| description | Mathematical modelling can provide precious tools for bioprocess simulation, prediction, control and optimization of mammalian cell-based cultures. In this paper we present a novel method to generate kinetic models of such cultures, rendering complex metabolic networks in a poly-pathway kinetic model. The model is based on subsets of elementary flux modes (EFMs) to generate macro-reactions. Thanks to our column generation-based optimization algorithm, the experimental data are used to identify the EFMs, which are relevant to the data. Here the systematic enumeration of all the EFMs is eliminated and a network including a large number of reactions can be considered. In particular, the poly-pathway model can simulate multiple metabolic behaviors in response to changes in the culture conditions.We apply the method to a network of 126 metabolic reactions describing cultures of antibody-producing Chinese hamster ovary cells, and generate a poly-pathway model that simulates multiple experimental conditions obtained in response to variations in amino acid availability. A good fit between simulated and experimental data is obtained, rendering the variations in the growth, product, and metabolite uptake/secretion rates. The intracellular reaction fluxes simulated by the model are explored, linking variations in metabolic behavior to adaptations of the intracellular metabolism. Keywords: Column generation, Optimization, Poly-pathway model, Kinetic modelling, Elementary flux mode, Chinese hamster ovary cell, Amino acid, Metabolic flux analysis |
| first_indexed | 2024-12-13T12:53:42Z |
| format | Article |
| id | doaj.art-fb578786e860473fb59627349fb1b916 |
| institution | Directory Open Access Journal |
| issn | 2214-0301 |
| language | English |
| last_indexed | 2024-12-13T12:53:42Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Metabolic Engineering Communications |
| spelling | doaj.art-fb578786e860473fb59627349fb1b9162022-12-21T23:45:15ZengElsevierMetabolic Engineering Communications2214-03012019-06-018Novel column generation-based optimization approach for poly-pathway kinetic model applied to CHO cell cultureErika Hagrot0Hildur Æsa Oddsdóttir1Meeri Mäkinen2Anders Forsgren3Véronique Chotteau4Cell Technology Group, Department of Industrial Biotechnology/Bioprocess Design, School of Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden; AdBIOPRO, VINNOVA Competence Centre for Advanced Bioproduction by Continuous Processing, SwedenDepartment of Mathematics, Division of Optimization and Systems Theory, KTH Royal Institute of Technology, Stockholm, SwedenCell Technology Group, Department of Industrial Biotechnology/Bioprocess Design, School of Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden; AdBIOPRO, VINNOVA Competence Centre for Advanced Bioproduction by Continuous Processing, SwedenDepartment of Mathematics, Division of Optimization and Systems Theory, KTH Royal Institute of Technology, Stockholm, SwedenCell Technology Group, Department of Industrial Biotechnology/Bioprocess Design, School of Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden; AdBIOPRO, VINNOVA Competence Centre for Advanced Bioproduction by Continuous Processing, Sweden; WCPR, Wallenberg Centre for Protein Research, Sweden; Corresponding author at: Cell Technology Group, Department of Industrial Biotechnology/Bioprocess Design, School of Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden.Mathematical modelling can provide precious tools for bioprocess simulation, prediction, control and optimization of mammalian cell-based cultures. In this paper we present a novel method to generate kinetic models of such cultures, rendering complex metabolic networks in a poly-pathway kinetic model. The model is based on subsets of elementary flux modes (EFMs) to generate macro-reactions. Thanks to our column generation-based optimization algorithm, the experimental data are used to identify the EFMs, which are relevant to the data. Here the systematic enumeration of all the EFMs is eliminated and a network including a large number of reactions can be considered. In particular, the poly-pathway model can simulate multiple metabolic behaviors in response to changes in the culture conditions.We apply the method to a network of 126 metabolic reactions describing cultures of antibody-producing Chinese hamster ovary cells, and generate a poly-pathway model that simulates multiple experimental conditions obtained in response to variations in amino acid availability. A good fit between simulated and experimental data is obtained, rendering the variations in the growth, product, and metabolite uptake/secretion rates. The intracellular reaction fluxes simulated by the model are explored, linking variations in metabolic behavior to adaptations of the intracellular metabolism. Keywords: Column generation, Optimization, Poly-pathway model, Kinetic modelling, Elementary flux mode, Chinese hamster ovary cell, Amino acid, Metabolic flux analysishttp://www.sciencedirect.com/science/article/pii/S2214030117300263 |
| spellingShingle | Erika Hagrot Hildur Æsa Oddsdóttir Meeri Mäkinen Anders Forsgren Véronique Chotteau Novel column generation-based optimization approach for poly-pathway kinetic model applied to CHO cell culture Metabolic Engineering Communications |
| title | Novel column generation-based optimization approach for poly-pathway kinetic model applied to CHO cell culture |
| title_full | Novel column generation-based optimization approach for poly-pathway kinetic model applied to CHO cell culture |
| title_fullStr | Novel column generation-based optimization approach for poly-pathway kinetic model applied to CHO cell culture |
| title_full_unstemmed | Novel column generation-based optimization approach for poly-pathway kinetic model applied to CHO cell culture |
| title_short | Novel column generation-based optimization approach for poly-pathway kinetic model applied to CHO cell culture |
| title_sort | novel column generation based optimization approach for poly pathway kinetic model applied to cho cell culture |
| url | http://www.sciencedirect.com/science/article/pii/S2214030117300263 |
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