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En Route for Systems Biology: In Silico Pathway Analysis and Metabolite Profiling

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Function and Regulation of Cellular Systems

Part of the book series: Mathematics and Biosciences in Interaction ((MBI))

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Abstract

With the developments in genomics there has been an increasing focus on the behaviour of complete biological systems and this has resulted in the development of Systems Biology as a new research field in biology [23]. Biological data from all levels of metabolism, such as genome, transcriptome, proteome, metabolome, any of the interactomes (protein-protein, protein-DNA, protein-mRNA, etc.) as well as the fluxome [25] are to be integrated in order to view a cell, an organism or even a population as a whole rather than investigating the single components of the system (Fig. 1). In order to integrate the wealth of information at the different levels of the metabolism, mathematical models play an important role, and Systems Biology is therefore often associated with quantitative investigation of the biological system under study. Much information on individual components, or sub-systems, in living cells has been obtained during the 20th century, but with tools such as DNA arrays, proteomics, metabolite profiling, it is now possible to analyse all the components in the system at the same time, thereby enabling a move from reductionist approaches to a global or a system approach [28].

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References

  1. Baxevanis, A.D. The molecular biology database collection: 2002 update, Nucleic Acids Res, 30 (2002), 1–12.

    Article  Google Scholar 

  2. Bernal, A., Ear, U., and Kyrpides, N. Genomes OnLine Database (GOLD): a monitor of genome projects world-wide, Nucleic Acids Res., 29 (2001), 126–127.

    Article  Google Scholar 

  3. Bertsimas, D. and Tsitsiklis, J.N. Linear optimization, (Belmont, Massachusetts: Athena Scientific), 1997.

    Google Scholar 

  4. Brent, R. Genomic biology, Cell, 100 (2000), 169–183.

    Article  Google Scholar 

  5. Burgard, A.P. and Maranas, C.D. Probing the Performance Limits of the Escherichia coli Metabolic Network Subject to Gene Additions or Deletions, Biotechnol. Bioeng., 74 (2001), 364–375.

    Article  Google Scholar 

  6. Christensen, B. and Nielsen, J. Metabolic network analysis. A powerful tool in metabolic engineering, Adv. Biochem. Eng Biotechnol., 66 (2000), 209–231.

    Google Scholar 

  7. Covert, M.W., Schilling, C.H., Famili, I., Edwards, J.S., Goryanin, I.I., Selkov, E., and Palsson, B.O. Metabolic modeling of microbial strains in silico, Trends Biochem. Sci., 26 (2001), 179–186.

    Article  Google Scholar 

  8. Edwards, J.S., Ibarra, R.U., and Palsson, B.O. In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data Nat. Biotechnol., 19 (2001), 125–130.

    Article  Google Scholar 

  9. Edwards, J.S. and Palsson, B.O. The Escherichia coli MG1655 in silico metabolic genotype: Its definition characteristics and capabilities Proc. Natl. Acad. Sci. U. S. A., 97 (2000), 5528–5533.

    Article  Google Scholar 

  10. Edwards, J.S., Ramakrishna, R., Schilling, C.H., and Palsson, B.O. Metabolic flux balance analysis In Metabolic Engineering, S.Y.Lee and E.T.Papoutsakis, eds. Marcel Dekker, (1999), pp. 13–57.

    Google Scholar 

  11. Endy, D. and Brent, R. Modelling cellular behaviour Nature, 409 (2001), 391–395.

    Article  Google Scholar 

  12. Entian, K.-D., Schuster, T., Hegemann, J.H., Becher, D., Feldmann, H., Gldener, U., Gtz, R., Hansen, M., Hollenberg, C.P., Jansen, G., Kramer, W., Klein, S., Ktter, P., Kricke, J., Launhardt, H., Mannhaupt, G., Maierl, A., Meyer, P., Mewes, W., Munder, T., Niedenthal, R.K., Ramezani Rad, M., Rhmer, A., Rmer, A., Rose, M., Schfer, B., Siegler, M.-L., Vetter, J., Wilhelm, N., Wolf, K., Zimmermann, F.K., Zollner, A., and Hinnen, A. Functional analysis of 150 deletion mutants in Saccharomyces cerevisiae by a systematic approach Mol. Gen. Genet., 262 (1999), 683–702.

    Article  Google Scholar 

  13. Famili, I., Förster, J., Nielsen, J., and Palsson, B.O. Computing phenotypes from a reconstructed genome-scale metabolic network for Saccharomyces cerevisiae PNAS (2003), in press.

    Google Scholar 

  14. Fell, DA. and Small, J. Fat synthesis in adipose tissue. An examination of stoichiometric constraints Biochem. J., 238 (1986), 781–786.

    Google Scholar 

  15. Fiehn, O. Combining genomics metabolome analysis and biochemical modelling to understand metabolic networks Comp. Funct. Genom., 2 (2001), 155–168.

    Article  Google Scholar 

  16. Fiehn, O., Kopka, J., Drmann, P., Altmann, T., Trethewey, R.N., and Willmitzer, L. Metabolite profiling for plant functional genomics Nat. Biotechnol., 18 (2000), 1157–1161.

    Article  Google Scholar 

  17. Förster, J., Famili, I., Fu, P., Palsson, B.O., and Nielsen, J. Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network Genome Res. 13 (2003), 244–253.

    Article  Google Scholar 

  18. Förster, J., Famili, I., Palsson, B.O., and Nielsen, J. Large-scale in silico evaluation of gene knockouts in Saccaromyces cerevisiae Omics 2 (2003), 193–203.

    Article  Google Scholar 

  19. Förster, J., Gombert, A.K., and Nielsen, H., A functional genomics approach using metabolomics and in silico pathway analysis Biotechnol. Bioeng., 79 (2002), 703–712.

    Article  Google Scholar 

  20. Gombert,A.K. and Nielsen,J., Mathematical modelling of metabolism. Curr. Opin. Biotechnol. 11 (2000), 180–186. Ideker,T., Galitski,T., and Hood,L. A NEW APPROACH TO DECODING LIFE: Systems Biology. Annu. Rev. Genomics Hum. Genet. 2 (2001), 343–372.

    Google Scholar 

  21. International Human Genome Sequencing Consortium Initial sequencing and analysis of the human genotne Nature, 409 (2001), 860–921.

    Article  Google Scholar 

  22. Juty, N.S., Spence, H.D., Hotz, H.R., Tang, H., Goryanin, L, and Hodgman, T.C. Simultaneous modelling of metabolic genetic and product-interaction networks Brief. Bioinform, 2 (2001), 223–232.

    Article  Google Scholar 

  23. Kitano, H. Perspectives on systems biology New Generat. Comput., 18 (2000), 199–216.

    Article  Google Scholar 

  24. Lee, S., Phalakornkule, C., Domach, M.M., and Grossmann, I.E. Recursive MILP Model For Finding All The Alternate Optima in LP Models For Metabolic Networks Computer & Chemical Engineering Science, 24 (2000), 711–716.

    Article  Google Scholar 

  25. Nielsen, J. and Olsson, L., An expanded role for microbial physiology in metabolic engineering and functional genomics: Moving towards systems biology FEMS Yeast Res., 2 (2002), 175–181.

    Google Scholar 

  26. O’Donovan, C., Apweiler, R., and Bairoch, A. The human proteomics initiative (HPI) Trends Biotechnol., 19 (2001), 178–181.

    Article  Google Scholar 

  27. Oliver, S.G., Winson, M.K., Kell, D.B., and Baganz, F. Systematic Functional Analysis of the Yeast Genome TIBTECH, 16 (1998), 373–378.

    Article  Google Scholar 

  28. Palsson, B.O. The challenges of in silico biology Nat. Biotechnol., 18 (2000), 1147–1150.

    Article  Google Scholar 

  29. Raamsdonk, L.M., Teusink, B., Broadhurst, D., Zhang, N., Hayes, A., Walsh, M.C., Berden, J.A., Brindle, K.M., Kell, D.B., Rowland, J.J., Westerhoff, H.V., van Dam, K., and Oliver, S.G., A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations Nat. Biotechnol., 19 (2001), 45–50.

    Article  Google Scholar 

  30. Reder, C. Metabolic control theory: a structural approach J. theor. Biol., 135 (1998), 175–201.

    Article  MathSciNet  Google Scholar 

  31. Roessner, U., Luedemann, A., Brust, D., Fiehn, O., Linke, T., Willmitzer, L., and Fernie, A. Metabolic profiling allows comprehensive phenotyping of genetically or environmentally modified plant systems Plant Cell, 13 (2001), 11–29.

    Google Scholar 

  32. Roessner, U., Wagner, C., Kopka, J., Trethewey, R.N., and Willmitzer, L. Technical advance: simultaneous analysis of metabolites in potato tuber by gas chromatography-mass spectrometry Plant J., 23 (2000), 131–142.

    Article  Google Scholar 

  33. Schilling, C.H. On systems biology and the pathway analysis of metabolic networks Ph.D.Thesis University of California, San Diego, USA, 2000.

    Google Scholar 

  34. Schilling, C.H., Letscher, D., and Palsson, B.O. Theory for the Systematic Definition of Metabolic Pathways and their use in Interpreting Metabolic Function from a Pathway-Oriented Perspective J. Theor. Biol., 203 (2000), 229–248.

    Article  Google Scholar 

  35. Schilling, C.H. and Palsson, B.O. Assessment of the Metabolic Capabilities of Haemophilus influenzae Rd through a Genome-scale Pathway Analysis J. Theor. Biol., 203 (2000), 249–283.

    Article  Google Scholar 

  36. Schuster, S., Dandekar, T., and Fell, D.A. Detection of elementary flux modes in biochemical networks: a promising tool for pathway analysis and metabolic engineering Trends Biochem. Sci. 17 (1999), 53–60.

    Google Scholar 

  37. Schuster, S., Fell, D.A., and Dandekar, T., A General Definition of Metabolic Pathways Useful for Systematic Organization and Analysis of Complex Metabolic Network Nature biotechnology, 18 (2000), 326–332.

    Article  Google Scholar 

  38. Schuster, S., Pfeiffer, T., Moldenhauer, F., Koch, I., and Dandekar, T. Exploring the pathway structure of metabolism: Decomposing into subnetworks and application to Mycoplasma pneurnoniae Bioinformatics, 2002, 351–361.

    Google Scholar 

  39. Schuster, St. and Hilgetag, C. On Elemtary Flux Modes in Biochemical Reaction Systems at Steady State Journal of Biological Systems, 2 (1994), 165–182.

    Article  Google Scholar 

  40. Stephanopoulos, G., Aristidou, A.A., and Nielsen, J. Metabolic engineering - Principles and methodologies San Diego: Academic Press, 1998.

    Google Scholar 

  41. Stuckrath, I., Lange, H.C., Kotter, P., van Gulik, W.M., Entian, K.D., and Heijnen, J.J. Characterization of null mutants of the glyoxylate cycle and gluconeogenic enzymes in S. cerevisiae through metabolic network modeling verified by chemostat cultivation Biotechnol. Bioeng., 77 (2002), 61–72.

    Article  Google Scholar 

  42. Szyperski, T. 13C-NMR MS and metabolic flux balancing in biotechnolgy research Quarterly Review of Biophysics, 31 (1998), 41–106.

    Article  Google Scholar 

  43. Tanaka, K., Hine, D.G., West-Dull, A., and Lynn, T.B. Gas-chromatographic method of analysis for urinary organic acids. I. Retention indices of 155 metabolically important compounds Clin. Chem., 26 (1980), 1839–1846.

    Google Scholar 

  44. Tomita, M. Whole-cell simulation: a grand challenge of the 21st century Trends Biotechnol., 19 (2001), 205–210.

    Article  Google Scholar 

  45. Tomita, M., Hashimoto, K., Takahashi, K., Shimizu, T.H., Matsuzaki, Y., Miyoshi, F., Saito, K., Tanida, S., Yugi, K., Venter, J.C., and Hutchsion, C.A. E-CELL: software environment for whole-cell simulation Bioinformatics, 15 (1999), 72–84.

    Article  Google Scholar 

  46. Trethewey, R.N. Gene discovery via metabolic profiling Curr. Opin. Biotechnol., 12 (2001), 135–138.

    Article  Google Scholar 

  47. Wiechert, W. 13C Metabolic Flux Analysis Metabolic Eng., 3 (2001), 195–206.

    Article  Google Scholar 

  48. Winzeler, E.A., Shoemaker, D.D., Astromoff, A., Liang, H., Anderson, K., Andre, B., Bangham, R., Benito, R., Boeke, J.D., Bussey, H., and Chu, A.M. Functional characterization of the S. cerevisiae genomne by gene deletion and parallel analysis Science, 285 (1999), 901–906.

    Article  Google Scholar 

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Authors and Affiliations

  1. Center for Process Biotechnology, BioCentrum-DTU, Technical University of Denmark, DK-2800, Lyngby, Denmark

    Jochen Förster, Mats Åkesson & Jens Nielsen

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  1. Jochen Förster
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  2. Mats Åkesson
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  3. Jens Nielsen
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Editors and Affiliations

  1. Zentrum für Hochleistungsrechnen, Technische Universität Dresden, Zellescher Weg 12, D-01069, Dresden, Germany

    Andreas Deutsch

  2. Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307, Dresden, Germany

    Jonathon Howard

  3. Department Theory (SF5), Hahn-Meitner-Institut Berlin, Glienicker Str. 100, D-14109, Berlin, Germany

    Martin Falcke

  4. Theoretische Physik, Universität des Saarlandes, Postfach 15 11 50, D-66041, Saarbrücken, Germany

    Walter Zimmermann

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Förster, J., Åkesson, M., Nielsen, J. (2004). En Route for Systems Biology: In Silico Pathway Analysis and Metabolite Profiling. In: Deutsch, A., Howard, J., Falcke, M., Zimmermann, W. (eds) Function and Regulation of Cellular Systems. Mathematics and Biosciences in Interaction. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-7895-1_5

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  • DOI: https://doi.org/10.1007/978-3-0348-7895-1_5

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9614-6

  • Online ISBN: 978-3-0348-7895-1

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