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DBRF-MEGN Method: An Algorithm for Inferring Gene Regulatory Networks from Large-Scale Gene Expression Profiles

  • Koji Kyoda
  • Shuichi Onami

Abstract

The difference-based regulation finding-minimum equivalent gene network (DBRF-MEGN) method is an algorithm for inferring gene regulatory networks from gene expression profiles corresponding to gene perturbations. In this method, gene regulatory networks are modeled as signed directed graphs, and the most parsimonious graphs consistent with gene expression profiles are deduced by using a graph theoretical procedure. The method is applicable to large-scale gene expression profiles, and gene regulatory networks deduced by the method are highly consistent with gene regulations identified through classic small-scale experiments in genetics and cell biology. Free software for the method is available and runs under Windows or Linux platforms on a typical IBM-compatible personal computer. The DBRF-MEGN method will provide invaluable information for basic biology and drug discovery.

Key Words

Gene network inference signed directed graph microarray gene expression profiles perturbation deletion mutant overexpression mutant 

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References

  1. 1.
    Liu H, Krizek J, Bretscher A. Construction of a GAL1-regulated yeast cDNA expression library and its application to the identification of genes whose overexpression causes lethality in yeast. Genetics 1992;132:665–673.PubMedGoogle Scholar
  2. 2.
    Baudin A, Ozier-Kalogeropoulos O, Denouel A, et al. A simple and efficient method for direct gene deletion in Saccharomyces cerevisiae. Nucleic Acids Res 1993;21:3329–3330.PubMedCrossRefGoogle Scholar
  3. 3.
    Wach A, Brachat A, Pohlmann R, et al. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast 1994;10:1793–1808.PubMedCrossRefGoogle Scholar
  4. 4.
    Lorenz MC, Muir RS, Lim E, et al. Gene disruption with PCR products in Saccharomyces cerevisiae. Gene 1995;158:113–117.PubMedCrossRefGoogle Scholar
  5. 5.
    Gari E, Piedrafita L, Aldea M, et al. A set of vectors with a tetracyclineregulatable promoter system for modulated gene expression in Saccharomyces cerevisiae. Yeast 1997;13:837–848.PubMedCrossRefGoogle Scholar
  6. 6.
    Fire A, Xu S, Montgomery MK, et al. Potent and specific genentic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998; 391:806–811.PubMedCrossRefGoogle Scholar
  7. 7.
    Schena M, Shalon D, Davis RW, et al. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995;270:467–470.PubMedCrossRefGoogle Scholar
  8. 8.
    Lockhart DJ, Dong H, Byrne MC, et al. Expression monitoring by hybridization to high-density oligonucleotide arrays. Nat Biotechnol 1996;14:1675–1680.PubMedCrossRefGoogle Scholar
  9. 9.
    Hughes TR, Marton MJ, Jones AR, et al. Functional discovery via a compendium of expression profiles. Cell 2000;102:109–126.PubMedCrossRefGoogle Scholar
  10. 10.
    Mnaimneh S, Davierwala AP, Haynes J, et al. Exploration of essential gene functions via titratable promoter alleles. Cell 2004;118:31–44.PubMedCrossRefGoogle Scholar
  11. 11.
    Ideker TE, Thorsson V, Karp RM. Discovery of regulatory interactions through perturbation: inference and experimental design. Pac Symp Biocomput 2000;305–316.Google Scholar
  12. 12.
    Pe’er D, Regev A, Elidan G, et al. Inferring subnetworks from perturbed expression profiles. Bioinformatics 2001;17Suppl:S215–S224.Google Scholar
  13. 13.
    Wagner A. How to reconstruct a large genetic network from n gene perturbations in fewer than n2 easy steps. Bioinformatics 2001;17:1183–1197.PubMedCrossRefGoogle Scholar
  14. 14.
    Kyoda K, Baba K, Onami S, et al. DBRF-MEGN method: an algorithm for deducing minimum equivalent gene networks from large-scale gene expression profiles of gene deletion mutants. Bioinformatics 2004;20:2662–2675.PubMedCrossRefGoogle Scholar
  15. 15.
    Breitkreutz BJ, Stark C, Tyers M. Osprey: a network visualization system. Genome Biol 2003;4:R22.PubMedCrossRefGoogle Scholar
  16. 16.
    Errede B, Ammerer G. STE12, a protein involved in cell-type-specific transcription and signal transduction in yeast, is a part of protein-DNA complexes. Genes Dev 1989;3:1349–1361.PubMedCrossRefGoogle Scholar
  17. 17.
    Sprague GFJr, Thorner JW. Pheromone response and signal transduction during the mating process of Saccharomyces cerevisiae. In: Jones EW, Pringle JR, Broach JR eds. The molecular and cellular biology of the yeast Saccharomyces. New York: Cold Spring Harbor Laboratory Press; 1992:657–744.Google Scholar
  18. 18.
    Oehlen LJ, McKinney JD, Cross FR. Ste12 and Mcm1 regulate cell cycle-dependent transcription of FAR1. Mol Cell Biol 1996;16:2830–2837.PubMedGoogle Scholar
  19. 19.
    Oehlen L, Cross FR. The mating factor response pathway regulates transcription of TEC1, a gene involved in pseudohyphal differentiation of Saccharomyces cerevisiae. FEBS Lett 1998;429:83–88.PubMedCrossRefGoogle Scholar
  20. 20.
    Ren B, Robert F, Wyrick JJ, et al. Genome-wide location and function of DNA binding proteins. Science 2000;290:2306–2309.PubMedCrossRefGoogle Scholar
  21. 21.
    Roberts CJ, Nelson B, Marton MJ, et al. Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles. Science 2000;287:873–880.PubMedCrossRefGoogle Scholar
  22. 22.
    Tedford K, Kim S, Sa D, et al. Regulation of the mating pheromone and invasive growth responses in yeast by two MAP kinase substrates. Curr Biol 1997;7:228–238.PubMedCrossRefGoogle Scholar
  23. 23.
    Elion EA. The Ste5p scaffold. J Cell Sci 2001;114:3967–3978.PubMedGoogle Scholar
  24. 24.
    Jenness DD, Burkholder AC, Hartwell LH. Binding of α-factor pheromone to yeast a cells: chemical and genetic evidence for an α-factor receptor. Cell 1983;35:521–529.PubMedCrossRefGoogle Scholar
  25. 25.
    Herskowitz I, Rine J, Strathern J. Mating-type determination and matingtype interconversion in Saccharomyces cerevisiae. In: Jones RW, Pringle JR, Broach JR, eds. The molecular and cellular biology of the yeast Saccharomyces. New York: Cold Spring Harbor Laboratory Press, 1992:319–414.Google Scholar
  26. 26.
    Ramer SW, Davis RW. A dominant truncation allele identifies a gene, STE20, that encodes a putative protein kinase necessary for mating in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 1993;90:452–456PubMedCrossRefGoogle Scholar
  27. 27.
    Elion EA, Brill JA, Fink GR. FUS3 represses CLN1 and CLN2 and in concert with KSS1 promotes signal transduction. Proc Natl Acad Sci USA 1991;88:9392–9396.PubMedCrossRefGoogle Scholar
  28. 28.
    Lee TI, Rinaldi NJ, Robert F, et al. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 2002;298:799–804.PubMedCrossRefGoogle Scholar
  29. 29.
    Farkas I, Jeong H, Vicsek T, et al. The topology of the transcriptional regulatory network in the yeast, Saccharomyces cerevisiae. Physica A 2003; 318:601–612.CrossRefGoogle Scholar
  30. 30.
    Ideker T, Thorsson V, Ranish JA, et al. Integrated genomic and proteomic analysis of a systematically perturbed metabolic network. Science 2001;292: 805–817.CrossRefGoogle Scholar
  31. 31.
    Gunsalus KC, Ge H, Schetter AJ, et al. Predictive model of molecular machines involved in Caenorhabditis elegans early embryogenesis. Nature 2005;436:861–865.PubMedCrossRefGoogle Scholar
  32. 32.
    Uetz P, Giot L, Gagney G, et al. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 2000;403:623–627.PubMedCrossRefGoogle Scholar
  33. 33.
    Ito T, Chiba T, Ozawa R, et al. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad Sci USA 2001;98: 4569–4574.PubMedCrossRefGoogle Scholar
  34. 34.
    Gavin AC, Bosche M, Krause R, et al. Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 2002;415: 141–147.PubMedCrossRefGoogle Scholar
  35. 35.
    Ho Y, Gruhler A, Helibut A, et al. Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 2002;415: 180–183.PubMedCrossRefGoogle Scholar
  36. 36.
    Huh WK, Falvo JV, Gerke LC, et al. Global analysis of protein localization in budding yeast. Nature 2003;425:686–691.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Koji Kyoda
    • 1
  • Shuichi Onami
    • 1
  1. 1.RIKEN Genomic Sciences Center (GSC)Yokohama InstituteYokohoma, KanagawaJapan

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