Home LiteratureArticle Details
PMID: 20177425 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Towards genome-scale signalling network reconstructions.

Nature reviews. Genetics ·Vol. 11 ·No. 4 ·2010-04-00 ·Pages 297-307

Hyduke DR, Palsson BØ

Abstract

Biological signalling networks allow living organisms to issue an integrated response to current conditions and make limited predictions about future environmental changes. Small-scale dynamic models of signalling cascades, including mitogen-activated protein kinase cascades, have been developed to generate hypotheses about signal transduction. Owing to technical limitations, these models and the hypotheses they generate have focused on a limited subset of signalling molecules. Now that we can simultaneously measure a substantial portion of the molecular components of a cell, we can begin to develop and test systems-level models of cellular signalling and regulatory processes, therefore gaining insights into the 'thought' processes of a cell.

MeSH Terms
Animals Gene Regulatory Networks Genomics Humans Metabolic Networks and Pathways Models, Biological Models, Genetic Signal Transduction/genetics Systems Biology
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hyduke Daniel R
Department of Bioengineering, University of California-San Diego, 9500 Gilman Drive, La Jolla, California 92093-0412, USA. [email protected]
Palsson Bernhard Ø
References (125)
125 references, click to expand
  1. A computational framework for the topological analysis and targeted disruption of signal transduction networks.
    Biophys J. 2006 Jul 1;91(1):382-98 PMID: 16617070
  2. Domains, motifs, and scaffolds: the role of modular interactions in the evolution and wiring of cell signaling circuits.
    Annu Rev Biochem. 2006;75:655-80 PMID: 16756506
  3. The JAK-STAT signaling network in the human B-cell: an extreme signaling pathway analysis.
    Biophys J. 2004 Jul;87(1):37-46 PMID: 15240442
  4. Constraint-based analysis of metabolic capacity of Salmonella typhimurium during host-pathogen interaction.
    BMC Syst Biol. 2009 Apr 08;3:38 PMID: 19356237
  5. Matrix formalism to describe functional states of transcriptional regulatory systems.
    PLoS Comput Biol. 2006 Aug 11;2(8):e101 PMID: 16895435
  6. Integrative model of the response of yeast to osmotic shock.
    Nat Biotechnol. 2005 Aug;23(8):975-82 PMID: 16025103
  7. Modular organization of protein interaction networks.
    Bioinformatics. 2007 Jan 15;23(2):207-14 PMID: 17092991
  8. Reconstruction of biochemical networks in microorganisms.
    Nat Rev Microbiol. 2009 Feb;7(2):129-43 PMID: 19116616
  9. Global alignment of multiple protein interaction networks with application to functional orthology detection.
    Proc Natl Acad Sci U S A. 2008 Sep 2;105(35):12763-8 PMID: 18725631
  10. The protein kinase complement of the human genome.
    Science. 2002 Dec 6;298(5600):1912-34 PMID: 12471243
  11. Origins and Mechanisms of miRNAs and siRNAs.
    Cell. 2009 Feb 20;136(4):642-55 PMID: 19239886
  12. Genetic screening for signal transduction in the era of network biology.
    Cell. 2007 Jan 26;128(2):225-31 PMID: 17254958
  13. Chemical combination effects predict connectivity in biological systems.
    Mol Syst Biol. 2007;3:80 PMID: 17332758
  14. Designing new cellular signaling pathways.
    Chem Biol. 2009 Mar 27;16(3):249-54 PMID: 19318206
  15. Protein-protein interaction as a predictor of subcellular location.
    BMC Syst Biol. 2009 Feb 25;3:28 PMID: 19243629
  16. Global reconstruction of the human metabolic network based on genomic and bibliomic data.
    Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1777-82 PMID: 17267599
  17. Modularity of stress response evolution.
    Proc Natl Acad Sci U S A. 2008 May 27;105(21):7500-5 PMID: 18495925
  18. Integrated network analysis identifies nitric oxide response networks and dihydroxyacid dehydratase as a crucial target in Escherichia coli.
    Proc Natl Acad Sci U S A. 2007 May 15;104(20):8484-9 PMID: 17494765
  19. Elucidating regulatory mechanisms downstream of a signaling pathway using informative experiments.
    Mol Syst Biol. 2009;5:287 PMID: 19584836
  20. Metabolic PathFinding: inferring relevant pathways in biochemical networks.
    Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W326-30 PMID: 15980483
  21. Influence of metabolic network structure and function on enzyme evolution.
    Genome Biol. 2006;7(5):R39 PMID: 16684370
  22. Unravelling the signal-transduction network in B lymphocytes.
    Nature. 2002 Dec 12;420(6916):708-10 PMID: 12478302
  23. Linking high-resolution metabolic flux phenotypes and transcriptional regulation in yeast modulated by the global regulator Gcn4p.
    Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6477-82 PMID: 19346491
  24. The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO.
    Curr Biol. 2004 Dec 29;14(24):2217-27 PMID: 15620648
  25. DNA repair, damage signaling and carcinogenesis.
    DNA Repair (Amst). 2008 Apr 2;7(4):670-80 PMID: 18221920
  26. Assembly of cell regulatory systems through protein interaction domains.
    Science. 2003 Apr 18;300(5618):445-52 PMID: 12702867
  27. A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway.
    Nat Cell Biol. 2004 Feb;6(2):97-105 PMID: 14743216
  28. A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology.
    Nat Biotechnol. 2008 Oct;26(10):1155-60 PMID: 18846089
  29. Comparative analysis reveals conserved protein phosphorylation networks implicated in multiple diseases.
    Sci Signal. 2009 Jul 28;2(81):ra39 PMID: 19638616
  30. Synthetic ecosystems based on airborne inter- and intrakingdom communication.
    Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10435-40 PMID: 17551014
  31. The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities.
    Proc Natl Acad Sci U S A. 2000 May 9;97(10):5528-33 PMID: 10805808
  32. Combinatorial RNAi for quantitative protein network analysis.
    Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6579-84 PMID: 17420474
  33. Prediction of phenotype and gene expression for combinations of mutations.
    Mol Syst Biol. 2007;3:96 PMID: 17389876
  34. Network biology: understanding the cell's functional organization.
    Nat Rev Genet. 2004 Feb;5(2):101-13 PMID: 14735121
  35. Defining genetic interaction.
    Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3461-6 PMID: 18305163
  36. Caught at its own game: regulatory small RNA inactivated by an inducible transcript mimicking its target.
    Genes Dev. 2009 Sep 1;23(17):2004-15 PMID: 19638370
  37. A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information.
    Mol Syst Biol. 2007;3:121 PMID: 17593909
  38. Systematic interpretation of genetic interactions using protein networks.
    Nat Biotechnol. 2005 May;23(5):561-6 PMID: 15877074
  39. Genome-scale gene/reaction essentiality and synthetic lethality analysis.
    Mol Syst Biol. 2009;5:301 PMID: 19690570
  40. Comparative genome-scale metabolic reconstruction and flux balance analysis of multiple Staphylococcus aureus genomes identify novel antimicrobial drug targets.
    J Bacteriol. 2009 Jun;191(12):4015-24 PMID: 19376871
  41. Identifying metabolic enzymes with multiple types of association evidence.
    BMC Bioinformatics. 2006 Mar 29;7:177 PMID: 16571130
  42. A synthetic oscillatory network of transcriptional regulators.
    Nature. 2000 Jan 20;403(6767):335-8 PMID: 10659856
  43. Systems approach to refining genome annotation.
    Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17480-4 PMID: 17088549
  44. Dynamic analysis of integrated signaling, metabolic, and regulatory networks.
    PLoS Comput Biol. 2008 May 23;4(5):e1000086 PMID: 18483615
  45. Linking the kinome and phosphorylome--a comprehensive review of approaches to find kinase targets.
    Mol Biosyst. 2008 Sep;4(9):920-33 PMID: 18704230
  46. Network motifs in the transcriptional regulation network of Escherichia coli.
    Nat Genet. 2002 May;31(1):64-8 PMID: 11967538
  47. Emergent properties of networks of biological signaling pathways.
    Science. 1999 Jan 15;283(5400):381-7 PMID: 9888852
  48. Development and experimental verification of a genome-scale metabolic model for Corynebacterium glutamicum.
    Microb Cell Fact. 2009 Aug 03;8:43 PMID: 19646286
  49. A synthetic gene-metabolic oscillator.
    Nature. 2005 May 5;435(7038):118-22 PMID: 15875027
  50. A subsystems-based approach to the identification of drug targets in bacterial pathogens.
    Prog Drug Res. 2007;64:131, 133-70 PMID: 17195474
  51. Global analyses of sumoylated proteins in Saccharomyces cerevisiae. Induction of protein sumoylation by cellular stresses.
    J Biol Chem. 2004 Jul 30;279(31):32262-8 PMID: 15166219
  52. Genetic regulatory mechanisms in the synthesis of proteins.
    J Mol Biol. 1961 Jun;3:318-56 PMID: 13718526
  53. A fragile metabolic network adapted for cooperation in the symbiotic bacterium Buchnera aphidicola.
    BMC Syst Biol. 2009 Feb 21;3:24 PMID: 19232131
  54. Rewiring the specificity of two-component signal transduction systems.
    Cell. 2008 Jun 13;133(6):1043-54 PMID: 18555780
  55. Saccharomyces cerevisiae phenotypes can be predicted by using constraint-based analysis of a genome-scale reconstructed metabolic network.
    Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13134-9 PMID: 14578455
  56. Model-driven evaluation of the production potential for growth-coupled products of Escherichia coli.
    Metab Eng. 2010 May;12(3):173-86 PMID: 19840862
  57. A single gene network accurately predicts phenotypic effects of gene perturbation in Caenorhabditis elegans.
    Nat Genet. 2008 Feb;40(2):181-8 PMID: 18223650
  58. Host-pathogen systems biology: logical modelling of hepatocyte growth factor and Helicobacter pylori induced c-Met signal transduction.
    BMC Syst Biol. 2008 Jan 14;2:4 PMID: 18194572
  59. The Database of Quantitative Cellular Signaling: management and analysis of chemical kinetic models of signaling networks.
    Bioinformatics. 2003 Feb 12;19(3):408-15 PMID: 12584128
  60. Topological analysis of mass-balanced signaling networks: a framework to obtain network properties including crosstalk.
    J Theor Biol. 2004 Mar 21;227(2):283-97 PMID: 14990392
  61. Synthetic gene networks that count.
    Science. 2009 May 29;324(5931):1199-202 PMID: 19478183
  62. Deciphering signaling outcomes from a system of complex networks.
    Sci Signal. 2009 May 19;2(71):ra22 PMID: 19454649
  63. A proteomics approach to understanding protein ubiquitination.
    Nat Biotechnol. 2003 Aug;21(8):921-6 PMID: 12872131
  64. Deterministic graph-theoretic algorithm for detecting modules in biological interaction networks.
    Int J Bioinform Res Appl. 2010;6(2):101-19 PMID: 20223734
  65. A genomic and functional inventory of deubiquitinating enzymes.
    Cell. 2005 Dec 2;123(5):773-86 PMID: 16325574
  66. The transcription unit architecture of the Escherichia coli genome.
    Nat Biotechnol. 2009 Nov;27(11):1043-9 PMID: 19881496
  67. Identification of potential pathway mediation targets in Toll-like receptor signaling.
    PLoS Comput Biol. 2009 Feb;5(2):e1000292 PMID: 19229310
  68. The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli.
    Nat Biotechnol. 2008 Jun;26(6):659-67 PMID: 18536691
  69. Systems analysis of metabolism in the pathogenic trypanosomatid Leishmania major.
    Mol Syst Biol. 2008;4:177 PMID: 18364711
  70. Engineering key components in a synthetic eukaryotic signal transduction pathway.
    Mol Syst Biol. 2009;5:270 PMID: 19455134
  71. Proteome survey reveals modularity of the yeast cell machinery.
    Nature. 2006 Mar 30;440(7084):631-6 PMID: 16429126
  72. RegulonDB (version 6.0): gene regulation model of Escherichia coli K-12 beyond transcription, active (experimental) annotated promoters and Textpresso navigation.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D120-4 PMID: 18158297
  73. Integrated analysis of regulatory and metabolic networks reveals novel regulatory mechanisms in Saccharomyces cerevisiae.
    Genome Res. 2006 May;16(5):627-35 PMID: 16606697
  74. Topological units of environmental signal processing in the transcriptional regulatory network of Escherichia coli.
    Proc Natl Acad Sci U S A. 2005 May 31;102(22):7841-6 PMID: 15908506
  75. Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway.
    Nat Genet. 2004 Apr;36(4):343-50 PMID: 14991053
  76. Reconstructing the ubiquitin network: cross-talk with other systems and identification of novel functions.
    Genome Biol. 2009;10(3):R33 PMID: 19331687
  77. Fault tolerance in protein interaction networks: stable bipartite subgraphs and redundant pathways.
    PLoS One. 2009;4(4):e5364 PMID: 19399174
  78. Conserved modular design of an oxygen sensory/signaling network with species-specific output.
    Proc Natl Acad Sci U S A. 2005 May 31;102(22):8018-23 PMID: 15911751
  79. Systems-level interactions between insulin-EGF networks amplify mitogenic signaling.
    Mol Syst Biol. 2009;5:256 PMID: 19357636
  80. Conserved pathways within bacteria and yeast as revealed by global protein network alignment.
    Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11394-9 PMID: 14504397
  81. iBsu1103: a new genome-scale metabolic model of Bacillus subtilis based on SEED annotations.
    Genome Biol. 2009;10(6):R69 PMID: 19555510
  82. Genome-scale reconstruction of Escherichia coli's transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization.
    PLoS Comput Biol. 2009 Mar;5(3):e1000312 PMID: 19282977
  83. Genome-scale analysis of Mannheimia succiniciproducens metabolism.
    Biotechnol Bioeng. 2007 Jul 1;97(4):657-71 PMID: 17405177
  84. Design of artificial cell-cell communication using gene and metabolic networks.
    Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2299-304 PMID: 14983004
  85. A fast, robust and tunable synthetic gene oscillator.
    Nature. 2008 Nov 27;456(7221):516-9 PMID: 18971928
  86. Properties of developmental gene regulatory networks.
    Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20063-6 PMID: 19104053
  87. Accelerating the reconstruction of genome-scale metabolic networks.
    BMC Bioinformatics. 2006 Jun 13;7:296 PMID: 16772023
  88. Construction of a genetic toggle switch in Escherichia coli.
    Nature. 2000 Jan 20;403(6767):339-42 PMID: 10659857
  89. A methodology for the structural and functional analysis of signaling and regulatory networks.
    BMC Bioinformatics. 2006 Feb 07;7:56 PMID: 16464248
  90. Integration of external signaling pathways with the core transcriptional network in embryonic stem cells.
    Cell. 2008 Jun 13;133(6):1106-17 PMID: 18555785
  91. Dissection of the insulin signaling pathway via quantitative phosphoproteomics.
    Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2451-6 PMID: 18268350
  92. Synthetic protein scaffolds provide modular control over metabolic flux.
    Nat Biotechnol. 2009 Aug;27(8):753-9 PMID: 19648908
  93. Variability and robustness in T cell activation from regulated heterogeneity in protein levels.
    Science. 2008 Aug 22;321(5892):1081-4 PMID: 18719282
  94. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.
    Cell. 2006 Nov 3;127(3):635-48 PMID: 17081983
  95. Modeling hybridoma cell metabolism using a generic genome-scale metabolic model of Mus musculus.
    Biotechnol Prog. 2005 Jan-Feb;21(1):112-21 PMID: 15903248
  96. Rapid evolution of functional complexity in a domain family.
    Sci Signal. 2009 Sep 08;2(87):ra50 PMID: 19738200
  97. Mechanisms of specificity in protein phosphorylation.
    Nat Rev Mol Cell Biol. 2007 Jul;8(7):530-41 PMID: 17585314
  98. Robustness and fragility in the yeast high osmolarity glycerol (HOG) signal-transduction pathway.
    Mol Syst Biol. 2009;5:281 PMID: 19536204
  99. Protein modules and signalling networks.
    Nature. 1995 Feb 16;373(6515):573-80 PMID: 7531822
  100. Systematic identification of functional orthologs based on protein network comparison.
    Genome Res. 2006 Mar;16(3):428-35 PMID: 16510899
  101. IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels.
    Nucleic Acids Res. 2009 Jan;37(Database issue):D680-5 PMID: 18948278
  102. Functional maps of protein complexes from quantitative genetic interaction data.
    PLoS Comput Biol. 2008 Apr 18;4(4):e1000065 PMID: 18421374
  103. DOMINE: a database of protein domain interactions.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D656-61 PMID: 17913741
  104. Integrating proteomic, transcriptional, and interactome data reveals hidden components of signaling and regulatory networks.
    Sci Signal. 2009 Jul 28;2(81):ra40 PMID: 19638617
  105. Conserved patterns of protein interaction in multiple species.
    Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):1974-9 PMID: 15687504
  106. A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases.
    BMC Bioinformatics. 2004 Jun 09;5:76 PMID: 15189570
  107. Systems biology of SNPs.
    Mol Syst Biol. 2006;2:38 PMID: 16820779
  108. Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae.
    BMC Syst Biol. 2009 Jan 14;3:7 PMID: 19144179
  109. Understanding complex signaling networks through models and metaphors.
    Prog Biophys Mol Biol. 2003 Jan;81(1):45-65 PMID: 12475569
  110. Circuit diagrams for biological networks.
    Mol Syst Biol. 2006;2:2006.0002 PMID: 16738549
  111. A comprehensive map of the toll-like receptor signaling network.
    Mol Syst Biol. 2006;2:2006.0015 PMID: 16738560
  112. Literature-curated protein interaction datasets.
    Nat Methods. 2009 Jan;6(1):39-46 PMID: 19116613
  113. Evolution of phosphoregulation: comparison of phosphorylation patterns across yeast species.
    PLoS Biol. 2009 Jun 16;7(6):e1000134 PMID: 19547744
  114. SNAPPI-DB: a database and API of Structures, iNterfaces and Alignments for Protein-Protein Interactions.
    Nucleic Acids Res. 2007 Jan;35(Database issue):D580-9 PMID: 17202171
  115. Architecture of transcriptional regulatory circuits is knitted over the topology of bio-molecular interaction networks.
    BMC Syst Biol. 2008 Feb 08;2:17 PMID: 18261202
  116. Reconstruction of cellular signalling networks and analysis of their properties.
    Nat Rev Mol Cell Biol. 2005 Feb;6(2):99-111 PMID: 15654321
  117. A genome-scale metabolic reconstruction of Mycoplasma genitalium, iPS189.
    PLoS Comput Biol. 2009 Feb;5(2):e1000285 PMID: 19214212
  118. Redefining the p53 response element.
    Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14373-8 PMID: 19597154
  119. Reconstruction and functional characterization of the human mitochondrial metabolic network based on proteomic and biochemical data.
    J Biol Chem. 2004 Sep 17;279(38):39532-40 PMID: 15205464
  120. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy.
    Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1888-93 PMID: 16443686
  121. Integrating high-throughput and computational data elucidates bacterial networks.
    Nature. 2004 May 6;429(6987):92-6 PMID: 15129285
  122. Hubba: hub objects analyzer--a framework of interactome hubs identification for network biology.
    Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W438-43 PMID: 18503085
  123. Determination of the Escherichia coli S-nitrosoglutathione response network using integrated biochemical and systems analysis.
    J Biol Chem. 2008 Feb 22;283(8):5148-57 PMID: 18070885
  124. Conservation and rewiring of functional modules revealed by an epistasis map in fission yeast.
    Science. 2008 Oct 17;322(5900):405-10 PMID: 18818364
  125. The BioGRID Interaction Database: 2008 update.
    Nucleic Acids Res. 2008 Jan;36(Database issue):D637-40 PMID: 18000002
Article Info
Journal
Nature reviews. Genetics
Abbr.
Nat Rev Genet
ISSN
1471-0064
DOI
10.1038/nrg2750
Email
[email protected]
Published
2010-04-00
Pages
297-307
Language
English
Region
England
NLM ID
100962779
Subset
IM
Grants
NIAID NIH HHS · Y1-AI-8401-01 · United States
External Links
PubMed source DOI: 10.1038/nrg2750 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2