1. 毕业设计（论文）的内容和要求

构建CHO细胞的小型代谢网络模型。

根据文献数据进行代谢通量分解和培养过程动态宏观反应模型。

2. 参考文献

赵权宇，于水燕，史吉平. 基元模式分析在生物网络与途径分析中的应用.生物工程学报，29(6),701-715, 2013. Ben Yahia, B., Malphettes, L., Heinzle, E. 2015. Macroscopic modeling of mammalian cell growth and metabolism. Applied Microbiology and Biotechnology, 99(17), 7009-7024. de Sousa, S.F., Bastin, G., Jolicoeur, M., Vande Wouwer, A. 2016. Dynamic metabolic flux analysis using a convex analysis approach: Application to hybridoma cell cultures in perfusion. Biotechnology and Bioengineering, 113(5), 1102-1112. Klamt, S., Saez-Rodriguez, J., Gilles, E.D. 2007. Structural and functional analysis of cellular networks with CellNetAnalyzer. BMC Syst Biol, 1, 2. Klamt, S., Schuster, S., Gilles, E.D. 2002. Calculability analysis in underdetermined metabolic networks illustrated by a model of the central metabolism in purple nonsulfur bacteria. Biotechnol Bioeng, 77(7), 734-51. Klamt, S., Stelling, J., Ginkel, M., Gilles, E.D. 2003. FluxAnalyzer: exploring structure, pathways, and flux distributions in metabolic networks on interactive flux maps. Bioinformatics, 19(2), 261-9. Nicolae, A., Wahrheit, J., Bahnemann, J., Zeng, A.P., Heinzle, E. 2014. Non-stationary 13C metabolic flux analysis of Chinese hamster ovary cells in batch culture using extracellular labeling highlights metabolic reversibility and compartmentation. BMC Syst Biol, 8, 50. Niu, H., Amribt, Z., Fickers, P., Tan, W., Bogaerts, P. 2013. Metabolic pathway analysis and reduction for mammalian cell cultures-Towards macroscopic modeling. Chemical Engineering Science, 102, 461-473. Okahashi, N., Kawana, S., Iida, J., Shimizu, H., Matsuda, F. 2016. GC-MS/MS survey of collision-induced dissociation of tert-butyldimethylsilyl-derivatized amino acids and its application to (13)C-metabolic flux analysis of Escherichia coli central metabolism. Anal Bioanal Chem, 408(22), 6133-40. Provost, A., Bastin, G., Agathos, S.N., Schneider, Y.J. 2006. Metabolic design of macroscopic bioreaction models: application to Chinese hamster ovary cells. Bioprocess Biosyst Eng, 29(5-6), 349-66. Zamorano, F., Wouwer, A.V., Jungers, R.M., Bastin, G. 2013. Dynamic metabolic models of CHO cell cultures through minimal sets of elementary flux modes. Journal of Biotechnology, 164(3), 409-422. Zhao, Q., Kurata, H. 2009. Maximum entropy decomposition of flux distribution at steady state to elementary modes. J Biosci Bioeng, 107(1), 84-9. Zhao, Q., Kurata, H. 2010. Use of maximum entropy principle with Lagrange multipliers extends the feasibility of elementary mode analysis. J Biosci Bioeng, 110(2), 254-61.

3. 毕业设计（论文）进程安排

1）~2018.1.13 完成开题报告 2）~2018.2.28 熟悉Matlab和 CellNetAnalyzer软件 3）~2018.3.31 构建CHO代谢网络模型并根据实验数据进行代谢通量分解 4）~2018.4.30 构建代谢宏观反应模型 5）~2018.5.31 撰写毕业论文 6）~2018.6 毕业答辩