The concept of Elementary Flux Modes (EFMs) has been of central importance in a number of studies involving the analysis of metabolism. In [1] this concept is used to translate the metabolic networks of the different phases of CHO cell culture into macroscopic bioreactions linking extracellular substrates to products. However, a critical issue concerns the calculation of these elementary flux vectors, as their number combinatorially increases with the size of the metabolic network. In this study, a detailed metabolic network of CHO cells is considered, where the above-mentioned combinatorial explosion makes the computation of the elementary flux modes impossible. To alleviate this problem, a methodology proposed in [10] is used to compute a decomposition of admissible flux vectors in a minimal number of elementary flux modes without explicitly enumerating all of them. As a result, a set of macroscopic bioreactions linking the extracellular measured species is obtained at a very low computational expense. The procedure is repeated for the several cell life phases and a global model is built using a multi-model approach, which is able to successfully predict the evolution of experimental data.
Zamorano, F., Vande Wouwer, A., Jungers, R., & Bastin, G. (2013). Dynamic metabolic models of CHO cell cultures through minimal sets of elementary flux modes. Journal of Biotechnology. Published. https://hdl.handle.net/2078.5/252299 (Original work published 2013)