Advertisement

Boolean Modelingof Genetic Regulatory Networks

  • Réka Albert
Part IV Biological Networks
Part of the Lecture Notes in Physics book series (LNP, volume 650)

Abstract

Biological systems form complex networks of interaction on several scales, ranging from the molecular to the ecosystem level. On the subcellular scale, interaction between genes and gene products (mRNAs, proteins) forms the basis of essential processes like signal transduction, cell metabolism or embryonic development. Recent experimental advances helped uncover the qualitative structure of many gene control networks, creating a surge of interest in the quantitative description of gene regulation. We give a brief description of the main frameworks and methods used in modeling gene regulatory networks, then focus on a recent model of the segment polarity genes of the fruit fly Drosophila melanogaster.

The basis of this model is the known interactions between the products of the segment polarity genes, and the network topology these interactions form. The interactions between mRNAs and proteins are described as logical (Boolean) functions. The success in reproducing both wild type and mutant gene expression patterns suggests that the kinetic details of the interactions are not essential as long as the network of interactions is unperturbed. The model predicts the gene patterns for cases that were not yet studied experimentally, and implies a remarkable robustness toward changes in internal parameters, initial conditions and even some mutations.

The success of this approach also suggests a wide applicability of real-topology-based Boolean modeling for gene regulatory networks. In cases when the information about the system is incomplete, Boolean modeling can verify the sufficiency of interactions and can propose ways to complete the network. After a coherent picture is obtained, more realistic kinetic models can be used to gain additional insights into the functioning of the system.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1. B. Alberts et al., Molecular Biology of the Cell, 4th edn. ( 2003).Google Scholar
  2. 2. L. Wolpert, R. Beddington, J. Brockes, T. Jessell, P. Lawrence and E. Meyerowitz, Principles of Development, (Current Biology Ltd., London 1998).Google Scholar
  3. 3. E.H. Davidson et al., Science 295, 1669 (2002).Google Scholar
  4. 4. S. A. Kauffman, J. Theor. Biol. 22, 437 (1969).Google Scholar
  5. 5. S. A. Kauffman, The origins of Order, (Oxford University Press, New York, 1993).Google Scholar
  6. 6. B. Derrida and Y. Pomeau, Europhys. Lett. 1, 45 (1986).Google Scholar
  7. 7. G. Weisbuch and D. Stauffer, J. Phys. (Paris) 48 11 (1987).Google Scholar
  8. 8. B. Luque and R. V. Solé, Phys. Rev. E 55, 257 (1997).Google Scholar
  9. 9. R. Albert and A.-L. Barabási, Phys. Rev. Lett. 84, 5660 (2000).Google Scholar
  10. 10. R. Thomas, J. Theor. Biol. 42, 563 (1973).Google Scholar
  11. 11. R. Thomas and R. D’Ari, Biological Feedback (CRC Press, Boca Raton, Ann Arbor, Boston, 1990).Google Scholar
  12. 12. L. Mendoza, D. Thieffry and E. R. Alvarez-Buylla, Bioinformatics 15, 593 (1999).Google Scholar
  13. 13. L. Sánchez and D. Thieffry, J. Theor. Biol. 211, 115 (2001).Google Scholar
  14. 14. A. Ghysen and R. Thomas, BioEssays 25, 802 (2003).Google Scholar
  15. 15. J. W. Bodnar, J. Theor. Biol. 188, 391 (1997).Google Scholar
  16. 16. J. W. Bodnar and M. K. Bradley, Cell Biochem. and Biophys. 34, 153 (2001).Google Scholar
  17. 17. C.-H. Yuh, H. Bolouri and E. H. Davidson, Development 128, 617 (2001).Google Scholar
  18. 18. R. Albert and H. G. Othmer, J. Theor. Biol 223, 1 (2003).Google Scholar
  19. 19. J. Reinitz and D. H. Sharp, Mechanisms of Development 49, 133 (1995).Google Scholar
  20. 20. G. von Dassow, E. Meir., E. M. Munro and G. M. Odell, Nature 406, 188 (2000).Google Scholar
  21. 21. V. V. Gursky, J. Reinitz and A. M. Samsonov, Chaos 11, 132 (2001).Google Scholar
  22. 22. P. W. Ingham and A. P. McMahon, Genes Dev. 15, 3059 (2001).Google Scholar
  23. 23. B. Sanson, EMBO Reports 2, 1083 (2001).Google Scholar
  24. 24. V. Hatini and S. DiNardo, Trends in Genetics 17, 574 (2001).Google Scholar
  25. 25. J. E. Hooper and M. P. Scott, The Molecular Genetic Basis of Positional Information in Insect Segments. In: Early Embryonic Development of Animals, ed. by W. Hennig (Springer, Berlin 1992) pp. 1-49.Google Scholar
  26. 26. K. M. Cadigan, U. Grossniklaus and W. J. Gehring, Genes Dev. 8, 899 (1994).Google Scholar
  27. 27. S. Pfeiffer and J.-P. Vincent, Cell & Dev. Biol. 10, 303 (1999).Google Scholar
  28. 28. K. M. Cadigan and R. Nusse, Genes Dev. 11, 3286 (1997).Google Scholar
  29. 29. T. Tabata, S. Eaton and T. B. Kornberg, Genes Dev. 6, 2635 (1992).Google Scholar
  30. 30. S. Eaton and T. B. Kornberg, Genes. Dev. 4, 1068 (1990).Google Scholar
  31. 31. A. Hidalgo and P. Ingham, Development 110, 291-301 (1990).Google Scholar
  32. 32. A. M. Taylor, Y. Nakano, J. Mohler and P. W. Ingham, Mechanisms of Development 42, 89 (1993).Google Scholar
  33. 33. M. van den Heuvel and P. W. Ingham, Nature 382, 547 (1996).Google Scholar
  34. 34. P. W. Ingham, EMBO J. 17, 3505 (1998).Google Scholar
  35. 35. P. Aza-Blanc and T. B. Kornberg, Trends in Genetics 15, 458 (1999).Google Scholar
  36. 36. J. T. Ohlmeyer and D. Kalderon, Nature 396, 749 (1998).Google Scholar
  37. 37. N. Méthot and K. Basler, Cell 96, 819 (1999).Google Scholar
  38. 38. C. Alexandre, A. Jacinto and P. W. Ingham, Genes Dev. 10, 2003 (1996).Google Scholar
  39. 39. T. von Ohlen and J. E. Hooper, Mechanisms of Development 68, 149 (1997).Google Scholar
  40. 40. P. W. Ingham, A. M. Taylor and Y. Nakano, Nature 353, 184 (1991).Google Scholar
  41. 41. J. Alcedo, Y. Zou and M. Noll, Molecular Cell 6, 457 (2000).Google Scholar
  42. 42. S. DiNardo, E. Sher, J. Heemskerk-Jongens, J. A. Kassis and P. H. O’Farrell, Nature 332, 45 (1988).Google Scholar
  43. 43. C. Schwartz, J. Locke, C. Nishida and T. B. Kornberg, Development 121, 1625 (1995).Google Scholar
  44. 44. A. Gallet, C. Angelats, S. Kerridge and P. P. Thérond, Development 127, 5509 (2000).Google Scholar
  45. 45. A. Martinez-Arias, N. Baker and P. W. Ingham, Development 103, 157 (1988).Google Scholar
  46. 46. A. Bejsovec and E. Wieschaus, Development 119 501 (1993).Google Scholar
  47. 47. J. Heemskerk, S. DiNardo, R. Kostriken and P. H. O’Farrell, Nature 352, 404 (1991).Google Scholar
  48. 48. A. Bejsovec and A. Martinez-Arias, Development 113, 471 (1991).Google Scholar
  49. 49. R. Laubenbacher and B. Stigler, Polynomial models for biochemical networks (preprint, 2003).Google Scholar
  50. 50. I. Shmulevich, E. Dougherty and W. Zhang, Proc. IEEE 90, 1778 (2002).Google Scholar

Authors and Affiliations

  • Réka Albert
    • 1
  1. 1.Department of Physics, Pennsylvania State University, University Park, PA 16802USA

Personalised recommendations