ArticleBioprocess and biosystems engineering2022
Genome-scale modeling of Chinese hamster ovary cells by hybrid semi-parametric flux balance analysis.
Article in Bioprocess and biosystems engineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 28 citations in OpenAlex.
- Toward a 4D genome annotation of CHO cells for biomanufacturing.Trends in biotechnology · 2026Review
- Systematic data-driven genome-scale metabolic model reduction for bioprocess modeling: CHO culture case study.NPJ systems biology and applications · 2026Article
- A Hybrid Modeling Framework for Predictive Digital Twins of CHO Cell Culture.Computational and structural biotechnology journal · 2026Article
- Flux Sampling Suggests Metabolic Signatures of High Antibody-Producing CHO Cells.Biotechnology and bioengineering · 2025Article
- Hybrid dynamic flux balance modeling approach for bioprocesses: an E. coli case study.Bioprocess and biosystems engineering · 2025Article
- Wheels turning: CHO cell modeling moves into a digital biomanufacturing era: Subtitle: CHO Metabolic Modeling.Computational and structural biotechnology journal · 2025Review
- Driving towards digital biomanufacturing by CHO genome-scale models.Trends in biotechnology · 2024Review
- From genotype to phenotype: computational approaches for inferring microbial traits relevant to the food industry.FEMS microbiology reviews · 2023Review
- Genome-scale models as a vehicle for knowledge transfer from microbial to mammalian cell systems.Computational and structural biotechnology journal · 2023Review
- Hybrid deep modeling of a CHO-K1 fed-batch process: combining first-principles with deep neural networks.Frontiers in bioengineering and biotechnology · 2023Article
- SBML2HYB: a Python interface for SBML compatible hybrid modeling.Bioinformatics (Oxford, England) · 2023Article
- Artificial intelligence-driven systems engineering for next-generation plant-derived biopharmaceuticals.Frontiers in plant science · 2023Review
- Recent advances in culture medium design for enhanced production of monoclonal antibodies in CHO cells: A comparative study of machine learning and systems biology approaches.Biotechnology advancesReview
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Flux balance analysis (FBA) is currently the standard method to compute metabolic fluxes in genome-scale networks. Several FBA extensions employing diverse objective functions and/or constraints have been published. Here we propose a hybrid semi-parametric FBA extension that combines mechanistic-level constraints (parametric) with empirical constraints (non-parametric) in the same linear program. A CHO dataset with 27 measured exchange fluxes obtained from 21 reactor experiments served to evaluate the method. The mechanistic constraints were deduced from a reduced CHO-K1 genome-scale network with 686 metabolites, 788 reactions and 210 degrees of freedom. The non-parametric constraints were obtained by principal component analysis of the flux dataset. The two types of constraints were integrated in the same linear program showing comparable computational cost to standard FBA. The hybrid FBA is shown to significantly improve the specific growth rate prediction under different constraints scenarios. A metabolically efficient cell growth feed targeting minimal byproducts accumulation was designed by hybrid FBA. It is concluded that integrating parametric and nonparametric constraints in the same linear program may be an efficient approach to reduce the solution space and to improve the predictive power of FBA methods when critical mechanistic information is missing.
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