RETRACTED: Poly-pathway model, a novel approach to simulate multiple metabolic states by reaction network-based model – Application to amino acid depletion in CHO cell culture

Abstract

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The authors of the paper wish to retract the paper due to the discovery of a calculation error in the processing of the raw data. The discovered error concerns the calculation of the specific uptake/secretion rates for several metabolites in one of the experimental conditions, i.e. glutamine omission (called Q0). In other words, in Figure 2, the variations of the metabolic fluxes for the condition Q0 are not correct. When this error is corrected, the resulting mathematical model changes (in particular for the results associated with Q0 conditions), several figures and tables are modified, and the interpretation of the fluxes in Q0 has to be slightly modified. Therefore the authors wish to retract the article. However, the error does not affect the modelling approach or the methodology presented in the article. Therefore, a revised version with the correct data has since been published: http://www.sciencedirect.com/science/article/pii/S0168165617302663. We apologize to the scientific community for the need to retract the article and the inconvenience caused.

CHO‐Omics Review: The Impact of Current and Emerging Technologies on Chinese Hamster Ovary Based Bioproduction

“…In effect, each cell line created could result in a novel metabolic state with different nutritional and environmental requirements. While several metabolic models have been applied to predict process and media changes, the power of these models is limited in any new cell line due to the genomic rearrangements that occur during the cell line development process. Integrating metabolomics data from high‐throughput metabolic analyses of clonal cell lines could be used to model and identify high performing cell lines.…”

Dynamic Modeling of CHO Cell Metabolism Using the Hybrid Cybernetic Approach With a Novel Elementary Mode Analysis Strategy

“…More so, CHO cell lines have shown to be stable, scalable, high-yield protein expression platforms with proper post-translational processing capabilities for several therapeutic applications (Nolan and Lee, 2011;Rodrigues et al, 2012;Kildegaard et al, 2013). However, productivity optimization is challenging, due to the intricate cellular machinery, compartmentalized metabolism and complex regulation and interconnection between multiple biological and media components that determine not only product quantity, but also quality (Palomares et al, 2004;Serrato et al, 2007;Hagrot et al, 2015). Systematic screening and derived statistical information have been useful, but often do not offer any insight on cell metabolism and regulation, making the exploration of multiple process and genetic modification targets difficult to assess and perform (Nolan and Lee, 2012;Hagrot et al, 2015).…”

“…Mathematical modeling of biological systems has been successfully used for assessing the metabolism complexity of many organisms while providing logical and systematic methods for growth and product enhancement (Haag et al, 2004;Naderi et al, 2010;Lee, 2011, 2012;Ghorbaniaghdam et al, 2014). On the past two decades, many different models have been introduced for CHO cell lines to study growth (Naderi et al, 2010;Zamorano et al, 2010Zamorano et al, , 2013Ahn and Antoniewicz, 2011;Meshram et al, 2011;Nicolae et al, 2015), media composition (Ahn and Antoniewicz, 2011;Nolan and Lee, 2011;Hagrot et al, 2015;Nicolae et al, 2015), culture parameters (Nolan and Lee, 2011;Martínez et al, 2015), determination of key metabolites for by-product accumulations (Nolan and Lee, 2012;Martínez et al, 2015), and amino acid metabolism (Zamorano et al, 2010(Zamorano et al, , 2013Ahn and Antoniewicz, 2011;Hagrot et al, 2015;Rejc et al, 2017). Within them, the most used modeling approaches, are metabolic flux analysis (MFA) and Flux Balance Analysis (FBA), which are based on pseudo-steady state mass flux balances (Nolan and Lee, 2011).…”

“…Up to this day, few dynamic metabolic models have been published for CHO cells with approaches such as mechanistic and hybrid models. Mechanistic models define algebraic expressions for the reaction rates as a function of metabolite concentrations but are often difficult to perform, as they generally rely on the estimation of a large number of kinetic parameters, and therefore usually limited to a small number of reactions (Nolan and Lee, 2012;Hagrot et al, 2015). On the other hand, hybrid models establish different culture stages and calculate the average flux on each step, along with MFA.…”

Metabolic Network Modelling of Chinese Hamster Ovary (CHO) Culture Bioreactors Operated as Microbial Cell Factories

“…2,5,[10][11][12][13][14][15][16][17] This knowledge has guided the researchers to develop several mathematical models, which are able to describe the fluxes within metabolic pathways. 4,[18][19][20][21][22][23] Analysis of fluxes usually focuses on measuring concentrations of extracellular metabolites. 13 Biocatalysis of substrates into commercially attractive products as well as byproducts is connected through pathways of cell metabolism.…”