Skip to main content

Bayesian Inference of Gene Regulatory Networks Using Gene Expression Time Series Data

  • Conference paper

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 4414))

Abstract

Differential equations have been established to model the dynamic behavior of gene regulatory networks in the last few years. They provide a detailed insight into regulatory processes at a molecular level. However, in a top down approach aiming at the inference of the underlying regulatory network from gene expression data, the corresponding optimization problem is usually severely underdetermined, since the number of unknowns far exceeds the number of timepoints available. Thus one has to restrict the search space in a biologically meaningful way.

We use differential equations to model gene regulatory networks and introduce a Bayesian regularized inference method that is particularly suited to deal with sparse and noisy datasets. Network inference is carried out by embedding our model into a probabilistic framework and maximizing the posterior probability. A specifically designed hierarchical prior distribution over interaction strenghts favours sparse networks, enabling the method to efficiently deal with small datasets.

Results on a simulated dataset show that our method correctly learns network structure and model parameters even for short time series. Furthermore, we are able to learn main regulatory interactions in the yeast cell cycle.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alberts, B., Johnson, J., Lewis, J., Raff, M., Roberts, K., Walker, P.: Molecular Biology of the Cell. Garland Publishing, New York (2002)

    Google Scholar 

  2. Baehler, J.: Cell-cycle control of gene expression in budding and fission yeast. Annu.Rev.Genet. 39, 69–94 (2005)

    Article  Google Scholar 

  3. Beal, M.J., Falciani, F., Ghahramani, Z., Rangel, C., Wild, D.L.: A bayesian approach to reconstructing genetic regulatory networks with hidden factors. Bioinformatics 21(3), 349–356 (2005)

    Article  Google Scholar 

  4. Bernard, A., Hartemink, A.J.: Informative structure priors: joint learning of dynamic regulatory networks from multiple types of data. In: Pacific Symposium on Biocomputing, pp. 459–470 (2005)

    Google Scholar 

  5. Chen, L., Aihara, K.: A Model of Periodic Oscillation for Genetic Regulatory Systems. IEEE Transactions on Circuits and Systems 49(10), 1429–1436 (2002)

    Article  MathSciNet  Google Scholar 

  6. Chen, C.C., Calzone, L., Csikasz-Nagy, A., Cross, F.R., Novak, B., Tyson, J.J.: Integrative Analysis of Cell Cycle Control in Budding Yeast. Mol.Biol.Cell 15(8), 3841–3862 (2004)

    Article  Google Scholar 

  7. Ermentrout, B.: Simulating, Analyzing and Animating Dynamical Systems: A Guide to XPPAUT for Researchers and Students, 1st edn. Soc. for Industrial & Applied Math (2002)

    Google Scholar 

  8. Gebert, J., Radde, N., Weber, G.-W.: Modeling gene regulatory networks with piecewise linear differential equations. In: EJOR, Chall.of Cont.Opt. in Theory and Applications (To appear, 2006)

    Google Scholar 

  9. Gebert, J., Radde, N.: Modeling procaryotic biochemical networks with differential equations. In: AIP Conference Proc. 839, 526–533 (2006)

    Google Scholar 

  10. Gouze, J.L.: Positive and negative circuits in dynamical systems. J.Biol.Sys. 6(21), 11–15 (1998)

    Article  MATH  Google Scholar 

  11. Guckenheimer, J., Holmes, P.: Nonlinear Oscillations, Dynamical Systems, and Bifurcations of Vector Fields. Springer, New York (1983)

    MATH  Google Scholar 

  12. Gustafsson, M., et al.: Constructing and analyzing a large-scale gene-to-gene regulatory network - Lasso constrained inference and biological validation. IEEE/ACM Trans. Comp. Biol. Bioinf. 2, 254–261 (2005)

    Article  Google Scholar 

  13. Jacob, F., Monod, J.: Genetic regulatory mechanisms in the synthesis of proteins. J.Mol.Biol. 3, 318–356 (1961)

    Article  Google Scholar 

  14. Kaderali, L., Zander, T., Faigle, U., Wolf, J., Schultze, J.L., Schrader, R.: CASPAR: A Hierarchical Bayesian Approach to predict Survival Times in Cancer from Gene Expression Data. Bioinformatics 22, 1495–1502 (2006)

    Article  Google Scholar 

  15. Kaderali, L.: A hierarchical Bayesian approach to regression and its application to predicting survival times in cancer. Shaker Verlag, Aachen (2006)

    MATH  Google Scholar 

  16. Li, F., Long, T., Lu, Y., Ouyang, Q., Tang, C.: The yeast cell-cycle is robustly designed. PNAS 101(14), 4781–4786 (2004)

    Article  Google Scholar 

  17. Luenberger, D.G.: Introduction to Dynamic Systems. John Wiley & Sons, Chichester (1979)

    MATH  Google Scholar 

  18. Radde, N., Gebert, J., Forst, C.V.: Systematic component selection for gene network refinement. Bioinformatics 22(21), 2674–2680 (2006)

    Article  Google Scholar 

  19. Rogers, S., Girolami, M.: A bayesian regression approach to the inference of regulatory networks from gene expression data. Bioinformatics 21(14), 3131–3137 (2005)

    Article  Google Scholar 

  20. Savageau, M., Alves, R.: Tutorial about “Mathematical Representation and Controlled Comparison of Biochemical Systems”. ICMSB2006, Muenchen (2006)

    Google Scholar 

  21. Spellman, P.T., Sherlock, G., et al.: Comprehenssive Identification of Cell Cycle-regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray Hybridization. Mol.Biol.Cell 9, 3273–3297 (1998)

    Google Scholar 

  22. Thomas, R.: On the relation between the logical structure of systems and their ability to generate mutliple steady states or sustained oscillations. Springer Series in Synergetics, vol. 9, pp. 180–193. Springer, Heidelberg (1981)

    Google Scholar 

  23. Tyson, J.J., Csikasz-Nagy, A., Novak, B.: The dynamics of cell cycle regulation. BioEssays 24, 1095–1109 (2002)

    Article  Google Scholar 

  24. Voit, E.: Computational Analysis of Biochemical Systems. Cambridge University Press, Cambridge

    Google Scholar 

  25. Yagil, G., Yagil, E.: On the relation between effector concentration and the rate of induced enzyme synthesis. Biophys.J. 11(1), 11–27 (1971)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Sepp Hochreiter Roland Wagner

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Berlin Heidelberg

About this paper

Cite this paper

Radde, N., Kaderali, L. (2007). Bayesian Inference of Gene Regulatory Networks Using Gene Expression Time Series Data. In: Hochreiter, S., Wagner, R. (eds) Bioinformatics Research and Development. BIRD 2007. Lecture Notes in Computer Science(), vol 4414. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-71233-6_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-71233-6_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-71232-9

  • Online ISBN: 978-3-540-71233-6

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics