Abstract
Genome-scale models have garnered considerable interest for their ability to elucidate cellular characteristics and lead to a better understanding of biological systems. Metabolic models in particular have been widely used to study complex metabolic pathways in order to better understand microbial systems and to design strategies for engineering various biotechnological applications. Similar to metabolic networks, transcriptional and signaling network models have also been reconstructed to elucidate regulatory interactions and to further understand the response of systems to various environmental stimuli. However, a true genome-scale model that integrates all these characteristics into one comprehensive model has not yet been constructed. For the time being, the existing network models have individually contributed to the knowledge of their respective fields and to our understanding of biological systems. In selected cases they have provided design strategies for systems wide engineering of metabolism. There have been several attempts to integrate these networks to realize the full potential of a complete cellular network model, although there is still room for further development. Here, we review the different network types and highlight their contributions to biotechnological applications via illustrative examples.
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References
Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BØ (2007) A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information. Mol Syst Biol 3:121
Sohn SB, Graf AB, Kim TY, Gasser B, Maurer M, Ferrer P, Mattanovich D, Lee SY (2010) Genome-scale metabolic model of methylotrophic yeast Pichia pastoris and its use for in silico analysis of heterologous protein production. Biotechnol J 5(7):705–715
Gianchandani EP, Joyce AR, Palsson BØ, Papin JA (2009) Functional states of the genome-scale Escherichia coli transcriptional regulatory system. PLoS Comput Biol 5(6):e1000403
Thiele I, Fleming RM, Bordbar A, Schellenberger J, Palsson BØ (2010) Functional characterization of alternate optimal solutions of Escherichia coli’s transcriptional and translational machinery. Biophys J 98(10):2072–2081
Park JH, Lee KH, Kim TY, Lee SY (2007) Metabolic engineering of Escherichia coli for the production of L-valine based on transcriptome analysis and in silico gene knockout simulation. Proc Natl Acad Sci USA 104(19):7797–7802
Becker J, Zelder O, Häfner S, Schröder H, Wittmann C (2011) From zero to hero–design-based systems metabolic engineering of Corynebacterium glutamicum for L-lysine production. Metab Eng 13(2):159–168
Cho BK, Zengler K, Qiu Y, Park YS, Knight EM, Barrett CL, Gao Y, Palsson BØ (2009) The transcription unit architecture of the Escherichia coli genome. Nat Biotechnol 27(11):1043–1049
Orth JD, Palsson BØ (2010) Systematizing the generation of missing metabolic knowledge. Biotechnol Bioeng 107(3):403–412
Bairoch A (2000) The ENZYME database in 2000. Nucleic Acids Res 28(1):304–305
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat Genet 25(1):25–29
Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M (2010) KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res 38(Database issue):D355–D360
Henry CS, DeJongh M, Best AA, Frybarger PM, Linsay B, Stevens RL (2010) High-throughput generation, optimization and analysis of genome-scale metabolic models. Nat Biotechnol 28(9):977–982
Caspi R, Altman T, Dale JM, Dreher K, Fulcher CA, Gilham F, Kaipa P, Karthikeyan AS, Kothari A, Krummenacker M, Latendresse M, Mueller LA, Paley S, Popescu L, Pujar A, Shearer AG, Zhang P, Karp PD (2010) The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res 38(Database issue):D473–D479
Price ND, Papin JA, Schilling CH, Palsson BØ (2003) Genome-scale microbial in silico models: the constraints-based approach. Trends Biotechnol 21(4):162–169
Orth JD, Thiele I, Palsson BØ (2010) What is flux balance analysis? Nat Biotechnol 28(3):245–248
Palsson BØ (2006) Systems biology: properties of reconstructed networks. Cambridge University Press, New York
Becker SA, Feist AM, Mo ML, Hannum G, Palsson BØ, Herrgård MJ (2007) Quantitative prediction of cellular metabolism with constraint-based models: the COBRA toolbox. Nat Protoc 2(3):727–738
Reed JL, Patel TR, Chen KH, Joyce AR, Applebee MK, Herring CD, Bui OT, Knight EM, Fong SS, Palsson BØ (2006) Systems approach to refining genome annotation. Proc Natl Acad Sci USA 103(46):17480–17484
Segre D, Vitkup D, Church GM (2002) Analysis of optimality in natural and perturbed metabolic networks. Proc Natl Acad Sci USA 99(23):15112–15117
Klamt S, Stelling J (2003) Two approaches for metabolic pathway analysis? Trends Biotechnol 21(2):64–69
Dandekar T, Moldenhauer F, Bulik S, Bertram H, Schuster S (2003) A method for classifying metabolites in topological pathway analyses based on minimization of pathway number. Biosystems 70(3):255–270
Lewis NE, Cho BK, Knight EM, Palsson BØ (2009) Gene expression profiling and the use of genome-scale in silico models of Escherichia coli for analysis: providing context for content. J Bacteriol 191(11):3437–3444
Ibarra RU, Edwards JS, Palsson BO (2002) Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth. Nature 420(6912):186–189
Edwards JS, Palsson BØ (1999) Systems properties of the Haemophilus influenzae Rd metabolic genotype. J Biol Chem 274(25):17410–17416
Duarte NC, Becker SA, Jamshidi N, Thiele I, Mo ML, Vo TD, Srivas R, Palsson BØ (2007) Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc Natl Acad Sci USA 104(6):1777–1782
Ma H, Sorokin A, Mazein A, Selkov A, Selkov E, Demin O, Goryanin I (2007) The Edinburgh human metabolic network reconstruction and its functional analysis. Mol Syst Biol 3:135
Edwards JS, Palsson BØ (2000) The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proc Natl Acad Sci USA 97(10):5528–5533
Reed JL, Vo TD, Schilling CH, Palsson BØ (2003) An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM/GPR). Genome Biol 4(9):R54.1–R54.12
Alper H, Jin YS, Moxley JF, Stephanopoulos G (2005) Identifying gene targets for the metabolic engineering of lycopene biosynthesis in Escherichia coli. Metab Eng 7(3):155–164
Choi HS, Lee SY, Kim TY, Woo HM (2010) In silico identification of gene amplification targets for improvement of lycopene production. Appl Environ Microbiol 76(10):3097–3105
Jung YK, Kim TY, Park SJ, Lee SY (2010) Metabolic engineering of Escherichia coli for the production of polylactic acid and its copolymers. Biotechnol Bioeng 105(1):161–171
Burgard AP, Pharkya P, Maranas CD (2003) Optknock: a bilevel programming framework for identifying gene knockout strategies for microbial strain optimization. Biotechnol Bioeng 84(6):647–657
Patil KR, Rocha I, Forster J, Nielsen J (2005) Evolutionary programming as a platform for in silico metabolic engineering. BMC Bioinformatics 6:308
Pharkya P, Burgard AP, Maranas CD (2004) OptStrain: a computational framework for redesign of microbial production systems. Genome Res 14(11):2367–2376
Melzer G, Esfandabadi ME, Franco-Lara E, Wittmann C (2009) Flux design: in silico design of cell factories based on correlation of pathway fluxes to desired properties. BMC Syst Biol 3:120
Feist AM, Zielinski DC, Orth JD, Schellenberger J, Herrgård MJ, Palsson BØ (2010) Model-driven evaluation of the production potential for growth-coupled products of Escherichia coli. Metab Eng 12(3):173–186
Fong SS, Burgard AP, Herring CD, Knight EM, Blattner FR, Maranas CD, Palsson BØ (2005) In silico design and adaptive evolution of Escherichia coli for production of lactic acid. Biotechnol Bioeng 91(5):643–648
Krömer JO, Wittmann C, Schröder H, Heinzle E (2006) Metabolic pathway analysis for rational design of L-methionine production by Escherichia coli and Corynebacterium glutamicum. Metab Eng 8(4):353–369
Kim TY, Kim HU, Park JM, Song H, Kim JS, Lee SY (2007) Genome-scale analysis of Mannheimia succiniciproducens metabolism. Biotechnol Bioeng 97(4):657–671
Kjeldsen KR, Nielsen J (2009) In silico genome-scale reconstruction and validation of the Corynebacterium glutamicum metabolic network. Biotechnol Bioeng 102(2):583–597
Alam MT, Merlo ME, Hodgson DA, Wellington EM, Takano E, Breitling R (2010) Metabolic modeling and analysis of the metabolic switch in Streptomyces coelicolor. BMC Genomics 11:202
Sohn SB, Kim TY, Park JM, Lee SY (2010) In silico genome-scale metabolic analysis of Pseudomonas putida KT2440 for polyhydroxyalkanoate synthesis, degradation of aromatics and anaerobic survival. Biotechnol J 5(7):739–750
Lee J, Yun H, Feist AM, Palsson BØ, Lee SY (2008) Genome-scale reconstruction and in silico analysis of the Clostridium acetobutylicum ATCC 824 metabolic network. Appl Microbiol Biotechnol 80(5):849–862
Lee KY, Park JM, Kim TY, Yun H, Lee SY (2010) The genome-scale metabolic network analysis of Zymomonas mobilis ZM4 explains physiological features and suggests ethanol and succinic acid production strategies. Microb Cell Fact 9:94
Schilling CH, Covert MW, Famili I, Church GM, Edwards JS, Palsson BØ (2002) Genome-scale metabolic model of Helicobacter pylori 26695. J Bacteriol 184(16):4582–4593
Kim HU, Kim SY, Jeong H, Kim TY, Kim JJ, Choy HE, Yi KY, Rhee JH, Lee SY (2011) Integrative genome-scale metabolic analysis of Vibrio vulnificus for drug targeting and discovery. Mol Syst Biol 7:460
Oberhardt MA, Puchalka J, Fryer KE, Martins dos Santos VA, Papin JA (2008) Genome-scale metabolic network analysis of the opportunistic pathogen Pseudomonas aeruginosa PAO1. J Bacteriol 190(8):2790–2803
Kim HU, Kim TY, Lee SY (2010) Genome-scale metabolic network analysis and drug targeting of multi-drug resistant pathogen Acinetobacter baumannii AYE. Mol Biosyst 6(2):339–348
Kim TY, Kim HU, Lee SY (2010) Metabolite-centric approaches for the discovery of antibacterials using genome-scale metabolic networks. Metab Eng 12(2):105–111
Kitano H (2007) A robustness-based approach to systems-oriented drug design. Nat Rev Drug Discov 6(3):202–210
Kitano H (2007) Biological robustness in complex host-pathogen systems. Prog Drug Res 64(239):241–263
Mo ML, Palsson BØ, Herrgård MJ (2009) Connecting extracellular metabolomic measurements to intracellular flux states in yeast. BMC Syst Biol 3:37
Duarte NC, Herrgård MJ, Palsson BØ (2004) Reconstruction and validation of Saccharomyces cerevisiae iND750, a fully compartmentalized genome-scale metabolic model. Genome Res 14(7):1298–1309
Dobson PD, Smallbone K, Jameson D, Simeonidis E, Lanthaler K, Pir P, Lu C, Swainston N, Dunn WB, Fisher P, Hull D, Brown M, Oshota O, Stanford NJ, Kell DB, King RD, Oliver SG, Stevens RD, Mendes P (2010) Further developments towards a genome-scale metabolic model of yeast. BMC Syst Biol 4:145
Zomorrodi AR, Maranas CD (2010) Improving the iMM904 S. cerevisiae metabolic model using essentiality and synthetic lethality data. BMC Syst Biol 4:178
Herrgard MJ, Swainston N, Dobson P, Dunn WB, Arga KY, Arvas M, Bluthgen N, Borger S, Costenoble R, Heinemann M, Hucka M, Le Novere N, Li P, Liebermeister W, Mo ML, Oliveira AP, Petranovic D, Pettifer S, Simeonidis E, Smallbone K, Spasic I, Weichart D, Brent R, Broomhead DS, Westerhoff HV, Kirdar B, Penttila M, Klipp E, Palsson BØ, Sauer U, Oliver SG, Mendes P, Nielsen J, Kell DB (2008) A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology. Nat Biotechnol 26(10):1155–1160
David H, Ozcelik IS, Hofmann G, Nielsen J (2008) Analysis of Aspergillus nidulans metabolism at the genome-scale. BMC Genomics 9:163
Selvarasu S, Karimi IA, Ghim GH, Lee DY (2010) Genome-scale modeling and in silico analysis of mouse cell metabolic network. Mol Biosyst 6(1):142–151
de Oliveira Dal’Molin CG, Quek LE, Palfreyman RW, Brumbley SM, Nielsen LK (2010) AraGEM, a genome-scale reconstruction of the primary metabolic network in Arabidopsis. Plant Physiol 152(2):579–589
Lewis NE, Schramm G, Bordbar A, Schellenberger J, Andersen MP, Cheng JK, Patel N, Yee A, Lewis RA, Eils R, Konig R, Palsson BØ (2010) Large-scale in silico modeling of metabolic interactions between cell types in the human brain. Nat Biotechnol 28(12):1279–1285
Shlomi T, Cabili MN, Herrgard MJ, Palsson BØ, Ruppin E (2008) Network-based prediction of human tissue-specific metabolism. Nat Biotechnol 26(9):1003–1010
Pabinger S, Rader R, Agren R, Nielsen J, Trajanoski Z (2011) MEMOSys: bioinformatics platform for genome-scale metabolic models. BMC Syst Biol 5(1):20
Thiele I, Palsson BØ (2010) A protocol for generating a high-quality genome-scale metabolic reconstruction. Nat Protoc 5(1):93–121
Shen-Orr SS, Milo R, Mangan S, Alon U (2002) Network motifs in the transcriptional regulation network of Escherichia coli. Nat Genet 31(1):64–68
Thiele I, Jamshidi N, Fleming RM, Palsson BØ (2009) Genome-scale reconstruction of Escherichia coli’s transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization. PLoS Comput Biol 5(3):e1000312
Covert MW, Knight EM, Reed JL, Herrgard MJ, Palsson BØ (2004) Integrating high-throughput and computational data elucidates bacterial networks. Nature 429(6987):92–96
Klamt S, Saez-Rodriguez J, Lindquist JA, Simeoni L, Gilles ED (2006) A methodology for the structural and functional analysis of signaling and regulatory networks. BMC Bioinformatics 7:56
Barrett CL, Herring CD, Reed JL, Palsson BØ (2005) The global transcriptional regulatory network for metabolism in Escherichia coli exhibits few dominant functional states. Proc Natl Acad Sci USA 102(52):19103–19108
Gianchandani EP, Papin JA, Price ND, Joyce AR, Palsson BO (2006) Matrix formalism to describe functional states of transcriptional regulatory systems. PLoS Comput Biol 2(8):e101
Bonneau R (2008) Learning biological networks: from modules to dynamics. Nat Chem Biol 4(11):658–664
Workman CT, Mak HC, McCuine S, Tagne JB, Agarwal M, Ozier O, Begley TJ, Samson LD, Ideker T (2006) A systems approach to mapping DNA damage response pathways. Science (New York, NY) 312(5776):1054–1059
Shlomi T, Eisenberg Y, Sharan R, Ruppin E (2007) A genome-scale computational study of the interplay between transcriptional regulation and metabolism. Mol Syst Biol 3:101
Herrgard MJ, Lee BS, Portnoy V, Palsson BØ (2006) Integrated analysis of regulatory and metabolic networks reveals novel regulatory mechanisms in Saccharomyces cerevisiae. Genome Res 16(5):627–635
Covert MW, Xiao N, Chen TJ, Karr JR (2008) Integrating metabolic, transcriptional regulatory and signal transduction models in Escherichia coli. Bioinformatics 24(18):2044–2050
Lee JM, Gianchandani EP, Eddy JA, Papin JA (2008) Dynamic analysis of integrated signaling, metabolic, and regulatory networks. PLoS Comput Biol 4(5):e1000086
Cho BK, Charusanti P, Herrgard MJ, Palsson BØ (2007) Microbial regulatory and metabolic networks. Curr Opin Biotechnol 18(4):360–364
Cho BK, Barrett CL, Knight EM, Park YS, Palsson BØ (2008) Genome-scale reconstruction of the Lrp regulatory network in Escherichia coli. Proc Natl Acad Sci USA 105(49):19462–19467
Gardner TS, di Bernardo D, Lorenz D, Collins JJ (2003) Inferring genetic networks and identifying compound mode of action via expression profiling. Science (New York, NY) 301(5629):102–105
Calvo JM, Matthews RG (1994) The leucine-responsive regulatory protein, a global regulator of metabolism in Escherichia coli. Microbiol Rev 58(3):466–490
Newman EB, Lin R (1995) Leucine-responsive regulatory protein: a global regulator of gene expression in E. coli. Annu Rev Microbiol 49:747–775
Covert MW, Palsson BØ (2002) Transcriptional regulation in constraints-based metabolic models of Escherichia coli. J Biol Chem 277(31):28058–28064
Grigoriev A (2003) On the number of protein-protein interactions in the yeast proteome. Nucleic Acids Res 31(14):4157–4161
Jeong H, Tombor B, Albert R, Oltvai ZN, Barabasi AL (2000) The large-scale organization of metabolic networks. Nature 407(6804):651–654
Wagner A, Fell DA (2001) The small world inside large metabolic networks. Proc Biol Sci 268(1478):1803–1810
Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di Francesco V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskern D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, McIntosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M, Pan S, Peck J, Peterson M, Rowe W, Sanders R, Scott J, Simpson M, Smith T, Sprague A, Stockwell T, Turner R, Venter E, Wang M, Wen M, Wu D, Wu M, Xia A, Zandieh A, Zhu X (2001) The sequence of the human genome. Science 291(5507):1304–1351
Schoeberl B, Eichler-Jonsson C, Gilles ED, Muller G (2002) Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors. Nat Biotechnol 20(4):370–375
Wiley HS, Shvartsman SY, Lauffenburger DA (2003) Computational modeling of the EGF-receptor system: a paradigm for systems biology. Trends Cell Biol 13(1):43–50
van Drogen F, Stucke VM, Jorritsma G, Peter M (2001) MAP kinase dynamics in response to pheromones in budding yeast. Nat Cell Biol 3(12):1051–1059
Blagoev B, Ong SE, Kratchmarova I, Mann M (2004) Temporal analysis of phosphotyrosine-dependent signaling networks by quantitative proteomics. Nat Biotechnol 22(9):1139–1145
Ho Y, Gruhler A, Heilbut A, Bader GD, Moore L, Adams SL, Millar A, Taylor P, Bennett K, Boutilier K, Yang L, Wolting C, Donaldson I, Schandorff S, Shewnarane J, Vo M, Taggart J, Goudreault M, Muskat B, Alfarano C, Dewar D, Lin Z, Michalickova K, Willems AR, Sassi H, Nielsen PA, Rasmussen KJ, Andersen JR, Johansen LE, Hansen LH, Jespersen H, Podtelejnikov A, Nielsen E, Crawford J, Poulsen V, Sorensen BD, Matthiesen J, Hendrickson RC, Gleeson F, Pawson T, Moran MF, Durocher D, Mann M, Hogue CW, Figeys D, Tyers M (2002) Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415(6868):180–183
Ideker T, Thorsson V, Ranish JA, Christmas R, Buhler J, Eng JK, Bumgarner R, Goodlett DR, Aebersold R, Hood L (2001) Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 292(5518):929–934
Boutros M, Kiger AA, Armknecht S, Kerr K, Hild M, Koch B, Haas SA, Paro R, Perrimon N (2004) Genome-wide RNAi analysis of growth and viability in Drosophila cells. Science 303(5659):832–835
Zheng L, Liu J, Batalov S, Zhou D, Orth A, Ding S, Schultz PG (2004) An approach to genomewide screens of expressed small interfering RNAs in mammalian cells. Proc Natl Acad Sci USA 101(1):135–140
Nielsen UB, Cardone MH, Sinskey AJ, MacBeath G, Sorger PK (2003) Profiling receptor tyrosine kinase activation by using Ab microarrays. Proc Natl Acad Sci USA 100(16):9330–9335
Meyer T, Teruel MN (2003) Fluorescence imaging of signaling networks. Trends Cell Biol 13(2):101–106
Hyduke DR, Palsson BØ (2010) Towards genome-scale signalling-network reconstructions. Nat Rev Genet 11(4):297–307
Li F, Thiele I, Jamshidi N, Palsson BØ (2009) Identification of potential pathway mediation targets in Toll-like receptor signaling. PLoS Comput Biol 5(2):e1000292
Madigan MT, Brock TD (2009) Brock biology of microorganisms, 12th edn. Pearson/Benjamin Cummings, San Francisco
Streif S, Oesterhelt D, Marwan W (2010) A predictive computational model of the kinetic mechanism of stimulus-induced transducer methylation and feedback regulation through CheY in archaeal phototaxis and chemotaxis. BMC Syst Biol 4:27
van Albada SB, Ten Wolde PR (2009) Differential affinity and catalytic activity of CheZ in E. coli chemotaxis. PLoS Comput Biol 5(5):e1000378
Zhang J, Xu Y, Shen J, Luo X, Chen J, Chen K, Zhu W, Jiang H (2005) Dynamic mechanism for the autophosphorylation of CheA histidine kinase: molecular dynamics simulations. J Am Chem Soc 127(33):11709–11719
Kremling A, Heermann R, Centler F, Jung K, Gilles ED (2004) Analysis of two-component signal transduction by mathematical modeling using the KdpD/KdpE system of Escherichia coli. Biosystems 78(1–3):23–37
Kremling A, Bettenbrock K, Gilles ED (2007) Analysis of global control of Escherichia coli carbohydrate uptake. BMC Syst Biol 1:42
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This work was supported by the Intelligent Synthetic Biology Center (2011-0031963) through the Global Frontier Project of Ministry of Education, Science and Technology.
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Lee, S.Y. et al. (2012). Genome-Scale Network Modeling. In: Wittmann, C., Lee, S. (eds) Systems Metabolic Engineering. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4534-6_1
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