{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:03:36Z","timestamp":1762898616681},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2010,6,10]],"date-time":"2010-06-10T00:00:00Z","timestamp":1276128000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2010,12]]},"DOI":"10.1186\/1752-0509-4-83","type":"journal-article","created":{"date-parts":[[2010,6,10]],"date-time":"2010-06-10T18:58:49Z","timestamp":1276196329000},"source":"Crossref","is-referenced-by-count":18,"title":["Monotonicity, frustration, and ordered response: an analysis of the energy landscape of perturbed large-scale biological networks"],"prefix":"10.1186","volume":"4","author":[{"given":"Giovanni","family":"Iacono","sequence":"first","affiliation":[]},{"given":"Claudio","family":"Altafini","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,6,10]]},"reference":[{"key":"472_CR1","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/msb.2008.8","volume":"4","author":"N Jamshidi","year":"2008","unstructured":"Jamshidi N, Palsson B: Formulating genome-scale kinetic models in the post-genome era. Mol Syst Biol. 2008, 4: 171- 10.1038\/msb.2008.8","journal-title":"Mol Syst Biol"},{"key":"472_CR2","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/nrm1838","volume":"7","author":"BN Kholodenko","year":"2006","unstructured":"Kholodenko BN: Cell-signalling dynamics in time and space. Nat Rev Mol Cell Biol. 2006, 7: 165-176. 10.1038\/nrm1838","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"17","key":"472_CR3","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1093\/bioinformatics\/btn337","volume":"24","author":"YK Kwon","year":"2008","unstructured":"Kwon YK, Cho KH: Coherent coupling of feedback loops: a design principle of cell signaling networks. Bioinformatics. 2008, 24 (17): 1926-1932. 10.1093\/bioinformatics\/btn337","journal-title":"Bioinformatics"},{"issue":"2","key":"472_CR4","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/nrm1570","volume":"6","author":"JA Papin","year":"2005","unstructured":"Papin JA, Hunter T, Palsson B\u00d8, Subramaniam S: Reconstruction of cellular signalling networks and analysis of their properties. Nat Rev Mol Cell Biol. 2005, 6 (2): 99-111. 10.1038\/nrm1570","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"5594","key":"472_CR5","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1126\/science.298.5594.824","volume":"298","author":"R Milo","year":"2002","unstructured":"Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U: Network motifs: simple building blocks of complex networks. Science. 2002, 298 (5594): 824-827. 10.1126\/science.298.5594.824","journal-title":"Science"},{"key":"472_CR6","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/ng881","volume":"31","author":"SS Shen-Orr","year":"2002","unstructured":"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. 10.1038\/ng881","journal-title":"Nat Genet"},{"key":"472_CR7","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/1471-2105-7-56","volume":"7","author":"S Klamt","year":"2006","unstructured":"Klamt S, Saez-Rodriguez J, Lindquist JA, Simeoni L, Gilles ED: A methodology for the structural and functional analysis of signaling and regulatory networks. BMC Bioinformatics. 2006, 7: 56-56. 10.1186\/1471-2105-7-56","journal-title":"BMC Bioinformatics"},{"key":"472_CR8","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1007\/978-3-540-68413-8_7","volume-title":"Formal Methods in Systems Biology","author":"F Fages","year":"2008","unstructured":"Fages F, Soliman S: From reaction models to influence graphs and back: a theorem. Formal Methods in Systems Biology. 2008, 90-102. full_text. Springer-Verlag LNBI 5054,"},{"key":"472_CR9","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1126\/science.1108876","volume":"309","author":"A Ma'ayan","year":"2005","unstructured":"Ma'ayan A, Jenkins SL, Neves S, Hasseldine A, Grace E, Dubin-Thaler B, Eungdamrong NJ, Weng G, Ram PT, Rice JJ, Kershenbaum A, Stolovitzky GA, Blitzer RD, Iyengar R: Formation of regulatory patterns during signal propagation in a Mammalian cellular network. Science. 2005, 309: 1078-1083. 10.1126\/science.1108876","journal-title":"Science"},{"key":"472_CR10","doi-asserted-by":"crossref","unstructured":"Samaga R, Saez-Rodriguez J, Alexopoulos LG, Sorger PK, Klamt S: The logic of EGFR\/ErbB signaling: theoretical properties and analysis of high-throughput data. PLoS Comput Biol. 2009, 5 (8):","DOI":"10.1371\/journal.pcbi.1000438"},{"key":"472_CR11","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1287\/mnsc.5.4.387","volume":"5","author":"F Harary","year":"1959","unstructured":"Harary F: Graph theoretic methods in the management sciences. Management Sci. 1959, 5: 387-403. 10.1287\/mnsc.5.4.387.","journal-title":"Management Sci"},{"key":"472_CR12","doi-asserted-by":"publisher","first-page":"311","DOI":"10.2307\/2295838","volume":"32","author":"J Quirk","year":"1965","unstructured":"Quirk J, Ruppert R: Qualitative economics and the stability of equilibrium. Rev Econ Stud. 1965, 32: 311-326. 10.2307\/2295838.","journal-title":"Rev Econ Stud"},{"issue":"3","key":"472_CR13","doi-asserted-by":"publisher","first-page":"036121","DOI":"10.1103\/PhysRevE.72.036121","volume":"72","author":"T Antal","year":"2005","unstructured":"Antal T, Krapivsky PL, Redner S: Dynamics of social balance on networks. Phys Rev E. 2005, 72 (3): 036121-10.1103\/PhysRevE.72.036121.","journal-title":"Phys Rev E"},{"key":"472_CR14","doi-asserted-by":"publisher","DOI":"10.1142\/0223","volume-title":"Spin Glasses and other frustrated systems","author":"D Chowdhury","year":"1986","unstructured":"Chowdhury D: Spin Glasses and other frustrated systems. 1986, Princeton University Press,"},{"key":"472_CR15","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511628771","volume-title":"Spin Glasses","author":"K Fischer","year":"1991","unstructured":"Fischer K, Hertz J: Spin Glasses. 1991, Cambridge University Press,"},{"key":"472_CR16","first-page":"DS8","volume-title":"Electr J Combinatorics","author":"T Zaslavsky","year":"1998","unstructured":"Zaslavsky T: Bibliography of signed and gain graphs. Electr J Combinatorics. 1998, DS8-"},{"key":"472_CR17","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1159\/000076100","volume":"1","author":"C Soul\u00e9","year":"2003","unstructured":"Soul\u00e9 C: Graphic Requirements for Multistationarity. ComplexUs. 2003, 1: 123-133. 10.1159\/000076100.","journal-title":"ComplexUs"},{"issue":"4","key":"472_CR18","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1093\/bib\/bbm028","volume":"8","author":"D Thieffry","year":"2007","unstructured":"Thieffry D: Dynamical roles of biological regulatory circuits. Brief Bioinform. 2007, 8 (4): 220-225. 10.1093\/bib\/bbm028","journal-title":"Brief Bioinform"},{"issue":"14","key":"472_CR19","doi-asserted-by":"publisher","first-page":"4781","DOI":"10.1073\/pnas.0305937101","volume":"101","author":"F Li","year":"2004","unstructured":"Li F, Long T, Lu Y, Ouyang Q, Tang C: The yeast cell-cycle network is robustly designed. Proc Natl Acad Sci USA. 2004, 101 (14): 4781-4786. 10.1073\/pnas.0305937101","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"472_CR20","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/j.jtbi.2005.01.023","volume":"235","author":"M Chaves","year":"2005","unstructured":"Chaves M, Albert R, Sontag ED: Robustness and fragility of Boolean models for genetic regulatory networks. J Theor Biol. 2005, 235 (3): 431-449. 10.1016\/j.jtbi.2005.01.023","journal-title":"J Theor Biol"},{"key":"472_CR21","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/s11693-007-9005-9","volume":"1","author":"ED Sontag","year":"2007","unstructured":"Sontag ED: Monotone and near-monotone biochemical networks. Systems and Synthetic Biology. 2007, 1: 59-87. 10.1007\/s11693-007-9005-9","journal-title":"Systems and Synthetic Biology"},{"key":"472_CR22","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1137\/1030003","volume":"30","author":"HL Smith","year":"1988","unstructured":"Smith HL: Systems of ordinary differential equations which generate an order preserving flow. A survey of results. SIAM Review. 1988, 30: 87-113. 10.1137\/1030003.","journal-title":"SIAM Review"},{"key":"472_CR23","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.biosystems.2006.08.001","volume":"90","author":"B DasGupta","year":"2007","unstructured":"DasGupta B, Enciso GA, Sontag E, Zhang Y: Algorithmic and complexity results for decompositions of biological networks into monotone subsystems. Biosystems. 2007, 90: 161-178. 10.1016\/j.biosystems.2006.08.001","journal-title":"Biosystems"},{"key":"472_CR24","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1049\/iet-syb:20070036","volume":"2","author":"A Ma'ayan","year":"2008","unstructured":"Ma'ayan A, Iyengar R, Sontag E: Proximity of Intracellular Regulatory Networks to Monotone. IET Systems Biology. 2008, 2: 103-112. 10.1049\/iet-syb:20070036","journal-title":"IET Systems Biology"},{"issue":"2","key":"472_CR25","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1529\/biophysj.107.125021","volume":"95","author":"E Sontag","year":"2008","unstructured":"Sontag E, Veliz-Cuba A, Laubenbacher R, Jarrah AS: The effect of negative feedback loops on the dynamics of boolean networks. Biophys J. 2008, 95 (2): 518-526. 10.1529\/biophysj.107.125021","journal-title":"Biophys J"},{"key":"472_CR26","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1049\/iet-syb.2009.0040","volume":"4","author":"G Iacono","year":"2010","unstructured":"Iacono G, Ramezani F, Soranzo N, Altafini C: Determining the distance to monotonicity of a biological network: a graph-theoretical approach. IET Systems Biology. 2010, 4: 223-235. 10.1049\/iet-syb.2009.0040","journal-title":"IET Systems Biology"},{"issue":"49","key":"472_CR27","doi-asserted-by":"publisher","first-page":"19235","DOI":"10.1073\/pnas.0805344105","volume":"105","author":"A Ma'ayan","year":"2008","unstructured":"Ma'ayan A, Cecchi GA, Wagner J, Rao AR, Iyengar R, Stolovitzky G: Ordered cyclic motifs contribute to dynamic stability in biological and engineered networks. Proc Natl Acad Sci USA. 2008, 105 (49): 19235-19240. 10.1073\/pnas.0805344105","journal-title":"Proc Natl Acad Sci USA"},{"key":"472_CR28","volume-title":"Understanding the control of metabolism","author":"D Fell","year":"1997","unstructured":"Fell D: Understanding the control of metabolism. 1997, Portland Press,"},{"key":"472_CR29","doi-asserted-by":"crossref","unstructured":"Thiele I, Jamshidi N, Fleming RM, Palsson B\u00d8: 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, 5 (3): 10.1371\/journal.pcbi.1000312.","DOI":"10.1371\/journal.pcbi.1000312"},{"key":"472_CR30","doi-asserted-by":"publisher","first-page":"3241","DOI":"10.1088\/0305-4470\/15\/10\/028","volume":"15","author":"F Barahona","year":"1982","unstructured":"Barahona F: On the computational complexity of Ising spin glass models. J Phys A Math Gen. 1982, 15: 3241-3253. 10.1088\/0305-4470\/15\/10\/028.","journal-title":"J Phys A Math Gen"},{"key":"472_CR31","first-page":"115","volume-title":"Communications on Physics","author":"G Toulouse","year":"1977","unstructured":"Toulouse G: Theory of the frustration effect in spin glasses: I. Communications on Physics. 1977, 2: 115."},{"issue":"23","key":"472_CR32","doi-asserted-by":"publisher","first-page":"14059","DOI":"10.1074\/jbc.273.23.14059","volume":"273","author":"S Roy","year":"1998","unstructured":"Roy S, Garges S, Adhya S: Activation and repression of transcription by differential contact: two sides of a coin. J Biol Chem. 1998, 273 (23): 14059-14062. http:\/\/www.hubmed.org\/display.cgi?uids=9603899 10.1074\/jbc.273.23.14059","journal-title":"J Biol Chem"},{"key":"472_CR33","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.tig.2004.11.004","volume":"21","author":"J Ma","year":"2005","unstructured":"Ma J: Crossing the line between activation and repression. Trends Genet. 2005, 21: 54-59. http:\/\/www.hubmed.org\/display.cgi?uids=15680515 10.1016\/j.tig.2004.11.004","journal-title":"Trends Genet"},{"issue":"3","key":"472_CR34","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1101\/gad.7.3.491","volume":"7","author":"K Han","year":"1993","unstructured":"Han K, Manley JL: Transcriptional repression by the Drosophila even-skipped protein: definition of a minimal repression domain. Genes Dev. 1993, 7 (3): 491-503. http:\/\/www.hubmed.org\/display.cgi?uids=8095483 10.1101\/gad.7.3.491","journal-title":"Genes Dev"},{"issue":"2","key":"472_CR35","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/S1369-5274(98)80005-2","volume":"1","author":"VA Rhodius","year":"1998","unstructured":"Rhodius VA, Busby SJ: Positive activation of gene expression. Curr Opin Microbiol. 1998, 1 (2): 152-159. http:\/\/www.hubmed.org\/display.cgi?uids=10066477 10.1016\/S1369-5274(98)80005-2","journal-title":"Curr Opin Microbiol"},{"issue":"36","key":"472_CR36","doi-asserted-by":"publisher","first-page":"13180","DOI":"10.1073\/pnas.0404775101","volume":"101","author":"A Stepchenko","year":"2004","unstructured":"Stepchenko A, Nirenberg M: Mapping activation and repression domains of the vnd\/NK-2 homeodomain protein. Proc Natl Acad Sci USA. 2004, 101 (36): 13180-13185. http:\/\/www.hubmed.org\/display.cgi?uids=15340160 10.1073\/pnas.0404775101","journal-title":"Proc Natl Acad Sci USA"},{"key":"472_CR37","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1126\/science.1062559","volume":"293","author":"CL Brooks","year":"2001","unstructured":"Brooks CL, Onuchic JN, Wales DJ: Statistical thermodynamics. Taking a walk on a landscape. Science. 2001, 293: 612-613. 10.1126\/science.1062559","journal-title":"Science"},{"issue":"3","key":"472_CR38","doi-asserted-by":"publisher","first-page":"031105","DOI":"10.1103\/PhysRevE.77.031105","volume":"77","author":"H Seyed-allaei","year":"2008","unstructured":"Seyed-allaei H, Seyed-allaei H, Ejtehadi MR: Energy-landscape networks of spin glasses. Physical Review E. 2008, 77 (3): 031105-10.1103\/PhysRevE.77.031105.","journal-title":"Physical Review E"},{"issue":"2","key":"472_CR39","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1140\/epjb\/e2002-00220-0","volume":"28","author":"M Leone","year":"2002","unstructured":"Leone M, V\u00e1zquez A, Vespignani A, Zecchina R: Ferromagnetic ordering in graphs with arbitrary degree distribution. Eur Phys J B. 2002, 28 (2): 191-197. 10.1140\/epjb\/e2002-00220-0.","journal-title":"Eur Phys J B"},{"issue":"2-3","key":"472_CR40","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/S0375-9601(02)01232-X","volume":"303","author":"G Bianconi","year":"2002","unstructured":"Bianconi G: Mean field solution of the Ising model on a Barab\u00e1si-Albert network. Phys Lett A. 2002, 303 (2-3): 166-168. 10.1016\/S0375-9601(02)01232-X.","journal-title":"Phys Lett A"},{"key":"472_CR41","doi-asserted-by":"publisher","first-page":"e147","DOI":"10.1371\/journal.pcbi.0020147","volume":"2","author":"J Wang","year":"2006","unstructured":"Wang J, Huang B, Xia X, Sun Z: Funneled landscape leads to robustness of cell networks: yeast cell cycle. PLoS Comput Biol. 2006, 2: e147- 10.1371\/journal.pcbi.0020147","journal-title":"PLoS Comput Biol"},{"key":"472_CR42","doi-asserted-by":"crossref","unstructured":"Salgado H, Gama-Castro S, Peralta-Gil M, Diaz-Peredo E, Sanchez-Solano F, Santos-Zavaleta A, Martinez-Flores I, Jimenez-Jacinto V, Bonavides-Martinez C, Segura-Salazar J, Martinez-Antonio A, Collado-Vides J: RegulonDB (version 5.0): Escherichia coli K-12 transcriptional regulatory network, operon organization, and growth conditions. Nucleic Acids Res. 2006, D394-D397. 34 Database,","DOI":"10.1093\/nar\/gkj156"},{"key":"472_CR43","doi-asserted-by":"publisher","first-page":"D93","DOI":"10.1093\/nar\/gkm910","volume":"36","author":"N Sierro","year":"2008","unstructured":"Sierro N, Makita Y, de Hoon M, Nakai K: DBTBS: a database of transcriptional regulation in Bacillus subtilis containing upstream intergenic conservation information. Nucleic Acids Res. 2008, 36: D93-96. 10.1093\/nar\/gkm910","journal-title":"Nucleic Acids Res"},{"key":"472_CR44","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1186\/1471-2105-8-429","volume":"8","author":"J Baumbach","year":"2007","unstructured":"Baumbach J: CoryneRegNet 4.0 - A reference database for corynebacterial gene regulatory networks. BMC Bioinformatics. 2007, 8: 429- 10.1186\/1471-2105-8-429","journal-title":"BMC Bioinformatics"},{"key":"472_CR45","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1038\/msb4100014","volume":"1","author":"K Oda","year":"2005","unstructured":"Oda K, Matsuoka Y, Funahashi A, Kitano H: A comprehensive pathway map of epidermal growth factor receptor signaling. Mol Syst Biol. 2005, 1: 2005- 10.1038\/msb4100014","journal-title":"Mol Syst Biol"},{"key":"472_CR46","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1038\/msb4100057","volume":"2","author":"K Oda","year":"2006","unstructured":"Oda K, Kitano H: A comprehensive map of the toll-like receptor signaling network. Mol Syst Biol. 2006, 2: 2006-0015. 10.1038\/msb4100057.","journal-title":"Mol Syst Biol"},{"issue":"9","key":"472_CR47","doi-asserted-by":"publisher","first-page":"R54","DOI":"10.1186\/gb-2003-4-9-r54","volume":"4","author":"JL Reed","year":"2003","unstructured":"Reed JL, Vo TD, Schilling CH, Palsson B\u00d8: An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM\/GPR). Genome Biol. 2003, 4 (9): R54- 10.1186\/gb-2003-4-9-r54","journal-title":"Genome Biol"},{"issue":"2","key":"472_CR48","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1101\/gr.234503","volume":"13","author":"J F\u00f6rster","year":"2003","unstructured":"F\u00f6rster J, Famili I, Fu P, Palsson B\u00d8, Nielsen J: Genome-scale Reconstruction of the Saccharomyces cerevisiae Metabolic Network. Genome Res. 2003, 13 (2): 244-253. 10.1101\/gr.234503","journal-title":"Genome Res"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-4-83.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1752-0509-4-83\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-4-83.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T01:19:56Z","timestamp":1559179196000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-4-83"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,10]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2010,12]]}},"alternative-id":["472"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-4-83","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,10]]},"article-number":"83"}}