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基于基因组规模代谢网络的计算建模及其在 CHO 细胞培养中的应用。

Computational modelling of genome-scale metabolic networks and its application to CHO cell cultures.

机构信息

Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia.

Faculty of Computer and Information Science, University of Ljubljana, Ljubljana, Slovenia.

出版信息

Comput Biol Med. 2017 Sep 1;88:150-160. doi: 10.1016/j.compbiomed.2017.07.005. Epub 2017 Jul 8.

DOI:10.1016/j.compbiomed.2017.07.005
PMID:28732234
Abstract

Genome-scale metabolic models (GEMs) have become increasingly important in recent years. Currently, GEMs are the most accurate in silico representation of the genotype-phenotype link. They allow us to study complex networks from the systems perspective. Their application may drastically reduce the amount of experimental and clinical work, improve diagnostic tools and increase our understanding of complex biological phenomena. GEMs have also demonstrated high potential for the optimisation of bio-based production of recombinant proteins. Herein, we review the basic concepts, methods, resources and software tools used for the reconstruction and application of GEMs. We overview the evolution of the modelling efforts devoted to the metabolism of Chinese Hamster Ovary (CHO) cells. We present a case study on CHO cell metabolism under different amino acid depletions. This leads us to the identification of the most influential as well as essential amino acids in selected CHO cell lines.

摘要

近年来,基因组规模代谢模型(GEM)变得越来越重要。目前,GEM 是基因型-表型联系的最准确的计算模拟。它们允许我们从系统的角度研究复杂的网络。它们的应用可以大大减少实验和临床工作的数量,改进诊断工具,并增加我们对复杂生物现象的理解。GEM 还展示了在生物基重组蛋白生产优化方面的巨大潜力。在此,我们综述了用于 GEM 重建和应用的基本概念、方法、资源和软件工具。我们概述了致力于中国仓鼠卵巢(CHO)细胞代谢建模工作的演变。我们展示了在不同氨基酸耗尽下 CHO 细胞代谢的案例研究。这使我们能够确定在选定的 CHO 细胞系中最有影响和必需的氨基酸。

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