Skip to main content

Reverse Engineering of Regulatory Relations in Gene Networks by a Probabilistic Approach

  • Conference paper
  • 893 Accesses

Part of the book series: Lecture Notes in Computer Science ((LNAI,volume 5571))

Abstract

In the last years microarray technology has revolutionised the fields of genetics, biotechnology and drug discovery. Due to its high parallelity, different analyses can be accomplished in one single experiment to generate vast amounts of data. In this paper we propose a new approach to solve the reverse engineering of regulatory relations task into gene networks from high-throughput data. We develop an Inference of Regulatory Interaction Schema (IRIS) algorithm that uses an iterative method to map gene expression profile values (steady-state and time-course) into discrete states, so that, a probabilistic approach can be used to infer gene interaction rules. IRIS provides two different descriptions of each regulatory relation: the description in which interactions are described as conditional probability tables (CPT-like) and descriptions in which regulations are truth tables (TT-like). We test IRIS on two synthetic networks and on real biological data showing its accuracy and efficiency.

At URL http://bioinformatics.biogem.it a Matlab implementation of IRIS is available.

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   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
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. Bensal, M., Bistro, V., Imposable, A.A., Bernardo, D.D.: How to Infer Gene Networks from Expression Profiles. Molecular System Biology 3, 78 (2007)

    Google Scholar 

  2. Basso, K., Margolin, A., Stolovitzky, G., Klein, U., Favera, R.D., Califano, A.: Reverse Engineering of Regulatory Networks in Human B Cells. Nature Genetics 37(4), 382–390 (2005)

    Article  Google Scholar 

  3. Basso, K., Margolin, A., Stolovitzky, G., Klein, U., Favera, R.D., Califano, A.: Inferring Gene Regulatory Networks Using Differential Evolution with Local Search Heuristics. IEEE Transaction on Computational Biology and Bioinformatics 4(4), 634–647 (2007)

    Article  Google Scholar 

  4. Gardner, T., Bernardo, D.D., Lorenz, D., Collins, J.: Inferring Genetic Networks and Identifying Compound Mode of Activation Via Expression Profiling. Science 301(5629), 102–105 (2003)

    Article  Google Scholar 

  5. Bernardo, D.D., Thompson, M., Gardner, T., Chobot, S., Eastwood, E., Wojtovich, A., Elliott, S., Schaus, S., Collins, J.: Chemogenomic Profiling on a Genome-Wide Scale Using Reverse-Engineered Gene Networks. Nature Biotechnology 39(23), 377–383 (2005)

    Article  Google Scholar 

  6. Bensal, M., Gatta, G.D., Bernardo, D.D.: Inference of Gene Regulatory Networks and Compound Mode of Action from Time Course Gene Expression Profiles. Bioinformatics 22(7), 815–822 (2006)

    Article  Google Scholar 

  7. Yu, J., Smith, V., Wang, P., Hartemink, A., Jarvis, E.: Advances to Bayesian Network Inference of Generating Casual Networks from Observational Biological Data. Bioinformatics 20, 3594–3603 (2004)

    Article  Google Scholar 

  8. Friedman, N., Linial, M., Nachman, I., Pe‘er, D.: Using Bayesian Networks to Analyze Expression Data. In: Proc. Fourth Annual Int. Conf. on Computational Molecular Biology, pp. 127–135. ACM Press, New York (2000)

    Google Scholar 

  9. Pe‘er, D., Regev, A., Elidan, G., Friedman, N.: Inferring Subnetowrks from perturbated Expression Profile. Bioinformatics 1(1), 1–9 (2001)

    Google Scholar 

  10. Ulitsky, I., Gat-Viks, I., Shamir, R.: MetaReg: A Platform for Modeling, Analysis and Visualization of Biological Systems Using Large-Scale Experimental Data. Genome Biology 9 (2008)

    Google Scholar 

  11. Dempster, A., Laird, N., Rubin, D.: Maximum Likelihood from Incomplete Data via the EM Algorithm. Journal of the Royal Statistical Society 39(1), 1–38 (1977)

    MathSciNet  MATH  Google Scholar 

  12. Lauritzen, S.: The EM Algorithm for Graphical Association Models with Missing Data 19 (1995)

    Google Scholar 

  13. Gat-Viks, I., Tanay, A., Shamir, R.: Modeling and Analysis of Heterogeneous Regulation in Biological Networks. In: Eskin, E., Workman, C. (eds.) RECOMB-WS 2004. LNCS (LNBI), vol. 3318, pp. 98–113. Springer, Heidelberg (2004)

    Chapter  Google Scholar 

  14. Frassen, B.V.: Relative Frequencies. Synthese 34(2), 133–166 (2004)

    Article  MathSciNet  Google Scholar 

  15. den Bulcke, T.V., Leemput, K.V., Naudts, B., van Remortel, P., Ma, H., Verschoren, A., Moor, B.D., Marchal, K.: SynTReN: a Generator of Synthetic Gene Expression Data for Design and Analysis of Structure Learning Algorithms. BMC Bioinformatics 7 (2006)

    Google Scholar 

  16. Kullback, S., Leibler, R.: On Information and Sufficiency. Annals of Mathematical Statistics (22), 79–86 (1951)

    Article  MathSciNet  MATH  Google Scholar 

  17. Spellman, P.T., Sherlock, G., Zhang, M.Q., Iyer, V.R., Anders, K., Eisen, M.B., Brown, P.O., Botsein, D., Futcher, B.: Comprehensive Identification of Cell Cycle-regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray Hybridization. Molecular Biology of the Cell 9(12), 3273–3297 (1998)

    Article  Google Scholar 

  18. Noman, N., Iba, H.: Inferring Gene Regulatory Networks Using Differential Evolution with Local Search Heuristics. IEEE Transaction on Computational Biology and Bioinformatics 4, 634–647 (2007)

    Article  Google Scholar 

  19. KEGG: (Kyoto Encyclopedia of Genes and Genomes), http://www.genome.ad.jp/kegg/

  20. Li, F., Long, T., Lu, Y., Tao, C.: The Yeast Cell Cycle Network is Robustly Designed. PNAS 101(14), 4781–4786 (2004)

    Article  Google Scholar 

  21. Kschischang, F.R., Brendan, J.F., Loeliger, H.A.: Factor Graphs and the Sum-Product Algorithm. IEEE Transactions on Information Theory 47(2), 498–519 (2001)

    Article  MathSciNet  MATH  Google Scholar 

  22. Schwob, E., Nasmyth, K.: CLB5 and CLB6, a new Pair of B Cyclins Involved in DNA Replication in Saccharomyces Cerevisiae. Genes and Development 7, 1160–1175 (1993)

    Article  Google Scholar 

  23. Di Como, C.J., Chang, H., Arndt, K.T.: Activation of CLN1 and CLN2 G1 cyclin gene expression by BCK2. Molecular and Cellular Biology 15(4), 1835–1846 (1995)

    Article  Google Scholar 

  24. Nugorho, T.T., Mendenhall, M.D.: An Inhibitor of Yeast Cyclin-dependent Protein Kinase Plays an Important Role in Ensuring the Genomic Integrity of Daughter Cells. Molecular and Cellular Biology 14(5), 3320–3328 (1994)

    Article  Google Scholar 

  25. Verma, R., Annan, R.S., Huddleston, M.J., Carr, S.A., Reynard, G., Deshaies, R.J.: Phosphorylation of Sic1p by G1 Cdk Required for Its Degradation and Entry into S Phase. Science 278(5337), 455–460 (1997)

    Article  Google Scholar 

  26. Amon, A., Tyers, M., Futcher, B., Nasmyth, K.: Mechanisms that Help the Yeast Cell Cycle Clock Tick: G2 Cyclins Transcriptionally Activate G2 Cyclins and Repress G1 Cyclins. Cell 74(6), 993–1007 (1993)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Ceccarelli, M., Morganella, S., Zoppoli, P. (2009). Reverse Engineering of Regulatory Relations in Gene Networks by a Probabilistic Approach. In: Di Gesù, V., Pal, S.K., Petrosino, A. (eds) Fuzzy Logic and Applications. WILF 2009. Lecture Notes in Computer Science(), vol 5571. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-02282-1_45

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-02282-1_45

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-02281-4

  • Online ISBN: 978-3-642-02282-1

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics