Constrain-based analysis of gene deletion on the metabolic flux redistribution of Saccharomyces Cerevisiae
- 1 State Key Laboratory of Bioelectronics, Southeast University
- 2 State Key Laboratory of Bioelectronics, Southeast University
Abstract
Based on the gene-protein-reaction (GPR) model of S. cerevisiae_iND750 and the method of constraint-based analysis, we first calculated the metabolic flux distribution of S. cere-visiae_iND750. Then we calculated the deletion impact of 438 calculable genes, one by one, on the metabolic flux redistribution of S. cere-visiae_iND750. Next we analyzed the correlation between v (describing deletion impact of one gene) and d (connection degree of one gene) and the correlation between v and Vgene (flux sum controlled by one gene), and found that both of them were not of linear relation. Furthermore, we sought out 38 important genes that most greatly affected the metabolic flux distribution, and determined their functional subsystems. We also found that many of these key genes were related to many but not several subsystems. Because the in silico model of S. cere-visiae_iND750 has been tested by many ex-periments, thus is credible, we can conclude that the result we obtained has biological sig-nificance.
- Bork, P. (2005) Is there biological research beyond Systems Biology? A comparative analysis of terms. Mol. Syst. Biol, 1, Art. No. 2005. 0012.
- Price ND, Papin JA, Schilling CH, Palsson BO. (2003) Genome-scale microbial in silico models: the constraints-based approach. Trends Biotechnol, 21 (4), 162-169.
- Price N D, Reed J L, Palsson B O. (2004) Genome-scale models of microbial cells: evaluating the consequences of constraints. Nature Reviews Microbiology, 2(11), 886-897.
- J.L. Reed, T.D. Vo, C.H. Schilling, and B.O. Palsson. (2003) An expanded genome scale model of Escherichia coli K-12 (iJR904 GSM/GPR). Genome Biology, 4, R54.1– R54.12.
- Feist, A.M., Henry, C.S., Reed, J.L., Krummenacker, M., Joyce, A.R., Karp, P.D., Broadbelt, L.J., Hatzimanikatis, V., Palsson, B.? (2007) A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information. Molecular Systems Biology, 3, Art. No. 121.
- Scott A Becker, Bernhard ?Palsson. (2005) Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation. BMC Microbiol, 5, Art. No. 8.
- Ines Thiele, Thuy D. Vo, Nathan D. Price, and Bernhard Palsson. (2005) Expanded metabolic reconstruction of Helicobacter pylori (iIT341 GSM/GPR): an in silico genome-scale characterization of single- and double- deletion mutants. Journal of Bacteriology, 187 (16), 5818-5830.
- Adam M Feist, Johannes C M Scholten, Bernhard Palsson, Fred J Brockman, Trey Ideker. (2006) Modeling methanogenesis with a genome-scale metabolic recon-struction of Methanosarcina barkeri. Molecular Systems Biology, 2, Art. No. 2006.0004.
- Natalie C. Duarte, Markus J. Herrgard and Bernhard Palsson. (2004) Reconstruction and validation of Saccharomyces cerevisiae iND750, a fully compartmentalized genome- scale metabolic model . Genome Res, 14 (7), 1298 -1309.
- Oh YK, Palsson BO, Park SM, Schilling CH, Mahadevan R. (2007) Genome-scale reconstruction of metabolic network in Bacillus subtilis based on high-throughput phenotyping and gene essentiality data. J Biol Chem, 282 (39), 28791-28799.
- Becker, S.A., Feist, A.M., Mo, M. L., Hannum, G., Palsson, B.O., Herrgard, M.J. (2007) Quantitative prediction of cellular metabolism with constraint-based models: The COBRA Toolbox. Nat. Protocols, 2(3), 727-738.
- Paul Shannon, Andrew Markiel, Owen Ozier, Nitin S. Baliga, Jonathan T. Wang, Daniel amage, Nada Amin, Benno Schwikowski and Trey Ideker. (2003) Cytoscape: a software environment for integrated models of biomo- lecular interaction networks. Genome Res, 13 (11), 2498-2504.