Multi-scale design and optimization of antibody production via flexible nets
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| Názov: | Multi-scale design and optimization of antibody production via flexible nets |
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| Autori: | Jorge Lázaro, Teresa Joven, Diana Széliová, Jürgen Zanghellini, Jorge Júlvez |
| Zdroj: | Comput Struct Biotechnol J Zaguán. Repositorio Digital de la Universidad de Zaragoza Universidad de Zaragoza |
| Informácie o vydavateľovi: | Elsevier BV, 2025. |
| Rok vydania: | 2025 |
| Predmety: | 104027 Computational chemistry, 301303 Medizinische Biochemie, Flexible nets, Formal models, CHO cells, Metabolic networks, Antibody production, 104027 Computational Chemistry, 106005 Bioinformatik, SDG 3 - Good Health and Well-being, SDG 3 – Gesundheit und Wohlergehen, 301303 Medical biochemistry, 106005 Bioinformatics, Research Article |
| Popis: | Antibodies are therapeutic proteins with many applications in medicine, such as treating viral infections, different types of cancer, and common diseases such as psoriasis and multiple sclerosis. Chinese Hamster Ovary (CHO) cells are the most widely used cells for antibody production due to their well-established use and favorable features. However, the current design of antibody production systems often relies on a "trial and error" approach to manipulate CHO cells. This approach is time-consuming and costly, and can lead to suboptimal process performance. The use of mathematical models has the potential to greatly accelerate and improve the design and optimization of antibody production. Starting from a systematic and formal approach, the aim is to achieve an automatic design of the whole process that allows optimal productivity to be reached. To this end, we develop mathematical models and methods for the design and optimization of antibody manufacturing systems. The mathematical models are based on Flexible Nets (FNs), a modeling formalism that accommodates uncertain parameters and nonlinear dynamics. FNs enable the development of comprehensive models that encompass both the metabolic network of CHO cells and the dynamics of the bioreactor in which the cells are cultured. Thus, by integrating macroscopic variables (e.g. dilution rate, substrate concentration, cell density, etc.) with microscopic variables (such as intracellular metabolic fluxes), our model represents a multi-scale system and facilitates global optimization. |
| Druh dokumentu: | Article Other literature type |
| Popis súboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 2001-0370 |
| DOI: | 10.1016/j.csbj.2025.03.040 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/40265159 http://zaguan.unizar.es/record/156541 https://ucrisportal.univie.ac.at/de/publications/c6fdb57e-8b30-48a1-a3a2-a36a2a9470a6 https://doi.org/10.1016/j.csbj.2025.03.040 |
| Rights: | CC BY |
| Prístupové číslo: | edsair.doi.dedup.....8ec4c7647bd30d8f8c21188f48e482cc |
| Databáza: | OpenAIRE |
| Abstrakt: | Antibodies are therapeutic proteins with many applications in medicine, such as treating viral infections, different types of cancer, and common diseases such as psoriasis and multiple sclerosis. Chinese Hamster Ovary (CHO) cells are the most widely used cells for antibody production due to their well-established use and favorable features. However, the current design of antibody production systems often relies on a "trial and error" approach to manipulate CHO cells. This approach is time-consuming and costly, and can lead to suboptimal process performance. The use of mathematical models has the potential to greatly accelerate and improve the design and optimization of antibody production. Starting from a systematic and formal approach, the aim is to achieve an automatic design of the whole process that allows optimal productivity to be reached. To this end, we develop mathematical models and methods for the design and optimization of antibody manufacturing systems. The mathematical models are based on Flexible Nets (FNs), a modeling formalism that accommodates uncertain parameters and nonlinear dynamics. FNs enable the development of comprehensive models that encompass both the metabolic network of CHO cells and the dynamics of the bioreactor in which the cells are cultured. Thus, by integrating macroscopic variables (e.g. dilution rate, substrate concentration, cell density, etc.) with microscopic variables (such as intracellular metabolic fluxes), our model represents a multi-scale system and facilitates global optimization. |
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| ISSN: | 20010370 |
| DOI: | 10.1016/j.csbj.2025.03.040 |
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