Abstract
Networks of interacting cellular components carry out the essential functions in living cells. Therefore, understanding the evolution and design principles of such complex networks is a central issue of systems biology. In recent years, structural analysis methods based on graph theory have revealed several intriguing features of such networks. In this chapter, we describe some of these structural analysis methods and show their application in analysis of biological networks, specifically metabolic and transcriptional regulatory networks (TRNs). We first explain the methods used for reconstruction of biological networks, and then compare the pros and cons of the different methods. It will be shown how graph theory-based methods can help to find the organization principle(s) of the networks, such as the power law degree distribution, the bow-tie connectivity structure, etc. Furthermore, we present an integrated network that includes the metabolite-protein (transcription factor) interaction to link the regulatory network with the metabolic network. This integrated network can provide more insights into the interaction patterns of cellular regulation.
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References
Kitano H. Computational systems biology. Nature 2002;420(6912):206–210.
Papin JA, Hunter T, Palsson BO, et al. Reconstruction of cellular signalling networks and analysis of their properties. Nat Rev Mol Cell Biol 2005;6(2):99–111.
Barabasi AL, Oltvai ZN. Network biology: understanding the cell’s functional organization. Nat Rev Genet 2004;5(2):101–113.
Herrgard MJ, Covert MW, Palsson BO. Reconstruction of microbial transcriptional regulatory networks. Curr Opin Biotechnol 2004;15(1):70–77.
Ma HW, Zeng AP. Reconstruction of metabolic networks from genome data and analysis of their global structure for various organisms. Bioinformatics 2003;19(2):270–277.
Alon U. Biological networks: the tinkerer as an engineer. Science 2003;301(5641):1866–1867.
Bray D. Molecular networks: the top-down view. Science 2003;301(5641):1864–1865.
Stelling J, Klamt S, Bettenbrock K, et al. Metabolic network structure determines key aspects of functionality and regulation. Nature 2002;420(6912):190–193.
Milo R, Shen-Orr S, Itzkovitz S, et al. Network motifs: simple building blocks of complex networks. Science 2002;298(5594):824–827.
Wagner A, Fell DA. The small world inside large metabolic networks. Proc R Soc Lond B Biol Sci 2001;268(1478):1803–1810.
Jeong H, Tombor B, Albert R, et al. The large-scale organization of metabolic networks. Nature 2000;407(6804):651–654.
Palsson BO. In silico biotechnology. Era of reconstruction and interrogation. Curr Opin Biotechnol 2004;15(1):50–51.
Forster J, Famili I, Fu P, Palsson BO, et al. Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. Genome Res 2003;13(2):244–253.
Kanehisa M, Goto S, Kawashima S, et al. The KEGG resource for deciphering the genome. Nucl Acids Res 2004;32(90001):D277–D280.
Karp PD, Riley M, Saier M, et al. The EcoCyc and MetaCyc databases. Nucleic Acids Res 2000;28(1):56–59.
Overbeek R, Larsen N, Pusch GD, et al. WIT: integrated system for high-throughput genome sequence analysis and metabolic reconstruction. Nucleic Acids Res 2000;28(1):123–125.
Sun J, Zeng AP. IdentiCS-identification of coding sequence and in silico reconstruction of the metabolic network directly from unannotated low-coverage bacterial genome sequence. BMC Bioinformatics 2004;5(1):112.
Schomburg I, Chang A, Ebeling C, et al. BRENDA, the enzyme database: updates and major new developments. Nucleic Acids Res 2004;32 (Database issue):D431–D433.
Gasteiger E, Gattiker A, Hoogland C, et al. ExPASy: the proteomics server for in-depth protein knowledge and analysis. Nucl Acids Res 2003;31(13):3784–3788.
Goto S, Okuno Y, Hattori M, et al. LIGAND: database of chemical compounds and reactions in biological pathways. Nucleic Acids Res 2002;30(1):402–404.
Karp P. Call for an enzyme genomics initiative. Genome Biol 2004;5(8):401.
Keseler IM, Collado-Vides J, Gama-Castro S, et al. EcoCyc: a comprehensive database resource for Escherichia coli. Nucleic Acids Res 2005;33 (Database issue):D334–D337.
Becker SA, Palsson BO. Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation. BMC Microbiol 2005;5(1):8.
Edwards JS, Palsson BO. The Escherichea coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proc Natl Acad Sci USA 2000;97(10):5528–5533.
Thiele I, Vo TD, Price ND, et al. Expanded metabolic reconstruction of Helicobacter pylori (iIT341 GSM/GPR): an in silico genome-scale characterization of single-and double-deletion mutants. J Bacteriol 2005;187(16):5818–5830.
von Mering C, Huynen M, Jaeggi D, et al. STRING: a database of predicted functional associations between proteins. Nucleic Acids Res 2003;31(1):258–261.
Yu H, Luscombe NM, Lu HX, et al. Annotation transfer between genomes: protein-protein interologs and protein-DNA regulogs. Genome Res 2004;14(6):1107–1118.
Salgado H, Gama-Castro S, Martinez-Antonio A, et al. RegulonDB (version 4.0): transcriptional regulation, operon organization and growth conditions in Escherichia coli K-12. Nucleic Acids Res 2004;32 Database issue:D303–D306.
Ishii T, Yoshida K, Terai G, et al. DBTBS: a database of Bacillus subtilis promoters and transcription factors. Nucleic Acids Res 2001;29(1):278–280.
Luscombe NM, Babu MM, Yu H, et al. Genomic analysis of regulatory network dynamics reveals large topological changes. Nature 2004;431(7006):308–312.
Guelzim N, Bottani S, Bourgine P, et al. Topological and causal structure of the yeast transcriptional regulatory network. Nat Genet 2002;31(1):60–63.
Makita Y, Nakao M, Ogasawara N, et al. DBTBS: database of transcriptional regulation in Bacillus subtilis and its contribution to comparative genomics. Nucleic Acids Res 2004;32 (Database issue):D75–D77.
Munch R, Hiller K, Barg H, et al. PRODORIC: prokaryotic database of gene regulation. Nucleic Acids Res 2003;31(1):266–269.
Matys V, Fricke E, Geffers R, et al. TRANSFAC: transcriptional regulation, from patterns to profiles. Nucleic Acids Res 2003;31(1):374–378.
Ma HW, Kumar B, Ditges U, et al. An extended transcriptional regulatory network of Escherichia coli and analysis of its hierarchical structure and network motifs. Nucleic Acids Res 2004;32(22):6643–6649.
Shen-Orr SS, Milo R, Mangan S, et al. Network motifs in the transcriptional regulation network of Escherichia coli. Nat Genet 2002;31(1):64–68.
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. Nucleic Acids Res 2006;34 (Database issue):D394–D397.
Salgado H, Santos-Zavaleta A, Gama-Castro S, et al. The comprehensive updated regulatory network of Escherichia coli K-12. BMC Bioinformatics 2006;7(1):5.
Herrgard MJ, Lee BS, Portnoy V, et al. Integrated analysis of regulatory and metabolic networks reveals novel regulatory mechanisms in Saccharomyces cerevisiae. Genome Res 2006;16(5):627–635.
Yeger-Lotem E, Sattath S, Kashtan N, et al. Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction. Proc Natl Acad Sci USA 2004;20;101(16):5934–5939.
Croes D, Couche F, Wodak SJ, et al. Metabolic PathFinding: inferring relevant pathways in biochemical networks. Nucleic Acids Res 2005;33 (Web Server issue):W326–W330.
Croes D, Couche F, Wodak SJ, et al. Inferring meaningful pathways in weighted metabolic networks. J Mol Biol 2006;356(1):222–236.
Arita M. In silico atomic tracing by substrate-product relationships in Escherichia coli intermediary metabolism. Genome Res 2003;13(11):2455–2466.
Arita M. The metabolic world of Escherichia coli is not small. Proc Natl Acad Sci U S A 2004;101(6):1543–1547.
Barrett CL, Price ND, Palsson BO. Network-level analysis of metabolic regulation in the human red blood cell using random sampling and singular value decomposition. BMC Bioinformatics 2006;7:132.
Wolf YI, Karev G, Koonin EV. Scale-free networks in biology: new insights into the fundamentals of evolution? Bioessays 2002;24(2):105–109.
Jeong H, Mason SP, Barabasi AL, et al. Lethality and centrality in protein networks. Nature 2001;411(6833):41–42.
Strogatz SH. Exploring complex networks. Nature 2001;410(6825):268–276.
Albert R, Barabasi AL. Topology of evolving networks: local events and universality. Phys Rev Lett 2000;85(24):5234–5237.
Van N, V, Snel B, Huynen MA. The yeast coexpression network has a small-world, scale-free architecture and can be explained by a simple model. EMBO Rep 2004;5(3):280–284.
Ma HW, Buer J, Zeng AP. Hierarchical structure and modular organisation in the Escherichia coli transcriptional regulatory network. BMC Bioinformatics 2004;2004.
Batagelj V, Mrvar A. Pajek. Program for Large Network Analysis. Connections 1998;21(2):47–57.
Ma HW, Zeng AP. Phylogenetic comparasion of metabolic capacities of organisms at genome level. Mol Phylogenet Evol 2004;31(1):204–213.
Ma HW, Zeng AP. The connectivity structure, giant strong component and centrality of metabolic networks. Bioinformatics 2003;19(11):1423–1430.
Freeman LC. Centrality in social networks: Conceptual clarification. Social Networks 1979;1:215–239.
Sabidussi G. The centrality index of a graph. Psychometrika 1966;31:58–603.
Holme P, Huss M, Jeong H. Subnetwork hierarchies of biochemical pathways. Bioinformatics 2003;19(4):532–538.
Broder A, Kumar R, Maghoul F, et al. Graph structure in the Web. Comp Networks 2000;33(1–6):309–320.
Csete M, Doyle J. Bow ties, metabolism and disease. Trends Biotechnol 2004;22(9):446–450.
Kitano H. Biological robustness. Nat Rev Genet 2004;5(11):826–837.
Martinez-Antonio A, Collado-Vides J. Identifying global regulators in transcriptional regulatory networks in bacteria. Curr Opin Microbiol 2003;6(5):482–489.
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Ma, Hw., da Silva, M.R., Sun, JB., Kumar, B., Zeng, AP. (2007). Reconstruction and Structural Analysis of Metabolic and Regulatory Networks. In: Choi, S. (eds) Introduction to Systems Biology. Humana Press. https://doi.org/10.1007/978-1-59745-531-2_7
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DOI: https://doi.org/10.1007/978-1-59745-531-2_7
Publisher Name: Humana Press
Print ISBN: 978-1-58829-706-8
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