Abstract
The availability of completely sequenced genomes and the wealth of literature on gene regulation have enabled researchers to model the transcriptional regulation system of some organisms in the form of a network. In order to reconstruct such networks in non-model organisms, three principal approaches have been taken. First, one can transfer the interactions between homologous components from a model organism to the organism of interest. Second, microarray experiments can be used to detect patterns in gene expression that stem from regulatory interactions. Finally, knowledge of experimentally characterized transcription factor binding sites can be used to analyze the promoter sequences in a genome in order to identify potential binding sites. In this chapter, we will focus in detail on the first approach and describe methods to reconstruct and analyze the transcriptional regulatory networks of uncharacterized organisms by using a known regulatory network as a template.
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References
Steinmetz LM, Davis RW. Maximizing the potential of functional genomics. Nat Rev Genet 2004, 5:190–201.
Quackenbush J. Computational analysis of microarray data. Nat Rev Genet 2001, 2:418–27.
Young RA. Biomedical discovery with DNA arrays. Cell 2000, 102:9–15.
Bulyk ML. DNA microarray technologies for measuring protein-DNA interactions. Curr Opin Biotechnol 2006, 17:422–30.
Harbison CT, Gordon DB, Lee TI, et al. Transcriptional regulatory code of a eukaryotic genome. Nature 2004, 431:99–104.
Lee TI, Rinaldi NJ, Robert F, et al. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 2002, 298:799–804.
Horak CE, Luscombe NM, Qian J, et al. Complex transcriptional circuitry at the G1/S transition in Saccharomyces cerevisiae. Genes Dev 2002, 16:3017–33.
Salgado H, Gama-Castro S, Peralta-Gil M, et al. RegulonDB (version 5.0): Escherichia coli K-12 transcriptional regulatory network, operon organization, and growth conditions. Nucl Acids Res 2006, 34:D394–97.
Baumbach J, Brinkrolf K, Czaja LF, Rahmann S, Tauch A. CoryneRegNet: An ontology-based data warehouse of corynebacterial transcription factors and regulatory networks. BMC Genomics 2006, 7:24.
Babu MM, Luscombe NM, Aravind L, Gerstein M, Teichmann SA. Structure and evolution of transcriptional regulatory networks. Curr Opin Struct Biol 2004, 14:283–91.
Barabasi AL, Oltvai ZN. Network biology: Understanding the cell's functional organization. Nat Rev Genet 2004, 5:101–13.
Madan Babu M, Teichmann SA, Aravind L. Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J Mol Biol 2006, 358:614–33.
Yu H, Luscombe NM, Lu HX, et al. Annotation transfer between genomes: Protein-protein interologs and protein-DNA regulogs. Genome Res 2004, 14:1107–18.
Lozada-Chavez I, Janga SC, Collado-Vides J. Bacterial regulatory networks are extremely flexible in evolution. Nucl Acids Res 2006, 34:3434–45.
Segal E, Shapira M, Regev A, et al. Module networks: Identifying regulatory modules and their condition-specific regulators from gene expression data. Nat Genet 2003, 34:166–76.
Gardner TS, di Bernardo D, Lorenz D, Collins JJ. Inferring genetic networks and identifying compound mode of action via expression profiling. Science 2003, 301:102–05.
Basso K, Margolin AA, Stolovitzky G, Klein U, Dalla-Favera R, Califano A. Reverse engineering of regulatory networks in human B cells. Nat Genet 2005, 37:382–90.
Wang SC. Reconstructing genetic networks from time ordered gene expression data using Bayesian method with global search algorithm. J Bioinform Comput Biol 2004, 2:441–58.
Qian J, Lin J, Luscombe NM, Yu H, Gerstein M. Prediction of regulatory networks: Genome-wide identification of transcription factor targets from gene expression data. Bioinformatics 2003, 19:1917–26.
Alkema WB, Lenhard B, Wasserman WW. Regulog analysis: Detection of conserved regulatory networks across bacteria: Application to Staphylococcus aureus. Genome Res 2004, 14:1362–73.
Wang T, Stormo GD. Identifying the conserved network of cis-regulatory sites of a eukaryotic genome. Proc Natl Acad Sci USA 2005, 102:17400–05.
Rodionov DA, Dubchak I, Arkin A, Alm E, Gelfand MS. Reconstruction of regulatory and metabolic pathways in metal-reducing delta-proteobacteria. Genome Biol 2004, 5:R90.
Bar-Joseph Z, Gerber GK, Lee TI, et al. Computational discovery of gene modules and regulatory networks. Nat Biotechnol 2003, 21:1337–42.
Xing B, van der Laan MJ. A statistical method for constructing transcriptional regulatory networks using gene expression and sequence data. J Comput Biol 2005, 12:229–46.
Haverty PM, Hansen U, Weng Z. Computational inference of transcriptional regulatory networks from expression profiling and transcription factor binding site identification. Nucl Acids Res 2004, 32:179–88.
Gao F, Foat BC, Bussemaker HJ. Defining transcriptional networks through integrative modeling of mRNA expression and transcription factor binding data. BMC Bioinformatics 2004, 5:31.
Bussemaker HJ, Li H, Siggia ED. Regulatory element detection using correlation with expression. Nat Genet 2001, 27:167–71.
Kim H, Hu W, Kluger Y. Unraveling condition specific gene transcriptional regulatory networks in Saccharomyces cerevisiae. BMC Bioinformatics 2006, 7:165.
Shen-Orr SS, Milo R, Mangan S, Alon U. Network motifs in the transcriptional regulation network of Escherichia coli. Nat Genet 2002, 31:64–68.
Albert R. Scale-free networks in cell biology. J Cell Sci 2005, 118:4947–57.
Teichmann SA, Babu MM. Gene regulatory network growth by duplication. Nat Genet 2004, 36:492–96.
Guelzim N, Bottani S, Bourgine P, Kepes F. Topological and causal structure of the yeast transcriptional regulatory network. Nat Genet 2002, 31:60–63.
Lespinet O, Wolf YI, Koonin EV, Aravind L. The role of lineage-specific gene family expansion in the evolution of eukaryotes. Genome Res 2002, 12:1048–59.
de Hoon MJ, Imoto S, Nolan J, Miyano S. Open source clustering software. Bioinformatics 2004, 20:1453–54.
Pavlidis P, Noble WS. Matrix2png: A utility for visualizing matrix data. Bioinformatics 2003, 19:295–96.
Altschul SF, Madden TL, Schaffer AA, et al. Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucl Acids Res 1997, 25:3389–402.
Kashtan N, Itzkovitz S, Milo R, Alon U. Efficient sampling algorithm for estimating subgraph concentrations and detecting network motifs. Bioinformatics 2004, 20:1746–58.
Makita Y, Nakao M, Ogasawara N, Nakai K. DBTBS: Database of transcriptional regulation in Bacillus subtilis and its contribution to comparative genomics. Nucl Acids Res 2004, 32:D75–77.
Baumbach J, Wittkop T, Rademacher K, Rahmann S, Brinkrolf K, Tauch A. CoryneRegNet 3.0-An interactive systems biology platform for the analysis of gene regulatory networks in corynebacteria and Escherichia coli. J Biotechnol 2007 Apr 30;129(2):279–89.
Balaji S, Babu MM, Iyer LM, Luscombe NM, Aravind L. Comprehensive analysis of combinatorial regulation using the transcriptional regulatory network of yeast. J Mol Biol 2006, 360:213–27.
Balaji S, Iyer LM, Aravind L, Babu MM. Uncovering a hidden distributed architecture behind scale-free transcriptional regulatory networks. J Mol Biol 2006, 360:204–12.
Acknowledgments
MMB acknowledges the Medical Research Council, UK, for financial support. LA acknowledges the Intramural Research Program of the NIH, NLM, NCBI, USA, for funding. We thank Arthur Wuster for critically reading this manuscript.
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Babu, M.M., Lang, B., Aravind, L. (2009). Methods to Reconstruct and Compare Transcriptional Regulatory Networks. In: Ireton, R., Montgomery, K., Bumgarner, R., Samudrala, R., McDermott, J. (eds) Computational Systems Biology. Methods in Molecular Biology, vol 541. Humana Press. https://doi.org/10.1007/978-1-59745-243-4_8
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DOI: https://doi.org/10.1007/978-1-59745-243-4_8
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