{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T08:48:32Z","timestamp":1762505312233},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2007,12,1]],"date-time":"2007-12-01T00:00:00Z","timestamp":1196467200000},"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":[[2007,12]]},"DOI":"10.1186\/1752-0509-1-57","type":"journal-article","created":{"date-parts":[[2007,12,6]],"date-time":"2007-12-06T19:13:26Z","timestamp":1196968406000},"source":"Crossref","is-referenced-by-count":32,"title":["Threshold-dominated regulation hides genetic variation in gene expression networks"],"prefix":"10.1186","volume":"1","author":[{"given":"Arne B","family":"Gjuvsland","sequence":"first","affiliation":[]},{"given":"Erik","family":"Plahte","sequence":"additional","affiliation":[]},{"given":"Stig W","family":"Omholt","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2007,12,6]]},"reference":[{"key":"57_CR1","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/0022-5193(72)90157-9","volume":"34","author":"L Glass","year":"1972","unstructured":"Glass L, Kauffman SA: Co-operative components, spatial localization and oscillatory cellular dynamics. Journal of Theoretical Biology. 1972, 34: 219-237. 10.1016\/0022-5193(72)90157-9","journal-title":"Journal of Theoretical Biology"},{"key":"57_CR2","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/0022-5193(73)90208-7","volume":"39","author":"L Glass","year":"1973","unstructured":"Glass L, Kauffman SA: The logical analysis of continuous, non-linear biochemical control networks. Journal of Theoretical Biology. 1973, 39: 103-129. 10.1016\/0022-5193(73)90208-7","journal-title":"Journal of Theoretical Biology"},{"issue":"3","key":"57_CR3","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1016\/0022-5193(73)90247-6","volume":"42","author":"R Thomas","year":"1973","unstructured":"Thomas R: Boolean Formalization of Genetic-Control Circuits. Journal of Theoretical Biology. 1973, 42 (3): 563-585. 10.1016\/0022-5193(73)90247-6","journal-title":"Journal of Theoretical Biology"},{"issue":"5358","key":"57_CR4","doi-asserted-by":"publisher","first-page":"1896","DOI":"10.1126\/science.279.5358.1896","volume":"279","author":"CH Yuh","year":"1998","unstructured":"Yuh CH, Bolouri H, Davidson EH: Genomic cis-Regulatory Logic: Experimental and Computational Analysis of a Sea Urchin Gene. Science. 1998, 279 (5358): 1896-1902. 10.1126\/science.279.5358.1896","journal-title":"Science"},{"issue":"6767","key":"57_CR5","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1038\/35002131","volume":"403","author":"T Gardner","year":"2000","unstructured":"Gardner T, Cantor C, Collins J: Construction of a genetic toggle switch in Escherichia coli. Nature. 2000, 403 (6767): 339-342. 10.1038\/35002131","journal-title":"Nature"},{"issue":"5","key":"57_CR6","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1242\/dev.128.5.617","volume":"128","author":"CH Yuh","year":"2001","unstructured":"Yuh CH, Bolouri H, Davidson EH: cis-regulatory logic in the endo16 gene: switching from a specification to a differentiation mode of control. Development. 2001, 128 (5): 617-629.","journal-title":"Development"},{"issue":"5572","key":"57_CR7","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1126\/science.1067407","volume":"296","author":"CC Guet","year":"2002","unstructured":"Guet CC, Elowitz MB, Hsing WH, Leibler S: Combinatorial synthesis of genetic networks. Science. 2002, 296 (5572): 1466-1470. 10.1126\/science.1067407","journal-title":"Science"},{"issue":"13","key":"57_CR8","doi-asserted-by":"publisher","first-page":"7702","DOI":"10.1073\/pnas.1230759100","volume":"100","author":"Y Setty","year":"2003","unstructured":"Setty Y, Mayo AE, Surette MG, Alon U: Detailed map of a cis-regulatory input function. PNAS. 2003, 100 (13): 7702-7707. 10.1073\/pnas.1230759100","journal-title":"PNAS"},{"issue":"4","key":"57_CR9","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1002\/bit.20142","volume":"87","author":"BP Kramer","year":"2004","unstructured":"Kramer BP, Fischer C, Fussenegger M: BioLogic gates enable logical transcription control in mammalian cells. Biotechnology and Bioengineering. 2004, 87 (4): 478-484. 10.1002\/bit.20142","journal-title":"Biotechnology and Bioengineering"},{"issue":"14","key":"57_CR10","doi-asserted-by":"publisher","first-page":"4954","DOI":"10.1073\/pnas.0409624102","volume":"102","author":"S Istrail","year":"2005","unstructured":"Istrail S, Davidson EH: Logic functions of the genomic cis-regulatory code. PNAS. 2005, 102 (14): 4954-4959. 10.1073\/pnas.0409624102","journal-title":"PNAS"},{"issue":"4","key":"57_CR11","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1371\/journal.pbio.0040045","volume":"4","author":"AE Mayo","year":"2006","unstructured":"Mayo AE, Setty Y, Shavit S, Zaslaver A, Alon U: Plasticity of the cis-Regulatory Input Function of a Gene. PLoS Biology. 2006, 4 (4): e45- 10.1371\/journal.pbio.0040045","journal-title":"PLoS Biology"},{"issue":"11","key":"57_CR12","doi-asserted-by":"publisher","first-page":"6840","DOI":"10.1073\/pnas.78.11.6840","volume":"78","author":"A Goldbeter","year":"1981","unstructured":"Goldbeter A, Koshland DE: An Amplified Sensitivity Arising from Covalent Modification in Biological Systems. PNAS. 1981, 78 (11): 6840-6844. 10.1073\/pnas.78.11.6840","journal-title":"PNAS"},{"issue":"3","key":"57_CR13","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/S1097-2765(00)00070-8","volume":"6","author":"FMV Rossi","year":"2000","unstructured":"Rossi FMV, Kringstein AM, Spicher A, Guicherit OM, Blau HM: Transcriptional control: Rheostat converted to on\/off switch. Molecular Cell. 2000, 6 (3): 723-728. 10.1016\/S1097-2765(00)00070-8","journal-title":"Molecular Cell"},{"key":"57_CR14","doi-asserted-by":"publisher","first-page":"3167","DOI":"10.1093\/emboj\/20.12.3167","volume":"20","author":"SR Biggar","year":"2001","unstructured":"Biggar SR, Crabtree GR: Cell signaling can direct either binary or graded transcriptional responses. The EMBO Journal. 2001, 20: 3167-3176. 10.1093\/emboj\/20.12.3167","journal-title":"The EMBO Journal"},{"issue":"5717","key":"57_CR15","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.1126\/science.1106914","volume":"307","author":"N Rosenfeld","year":"2005","unstructured":"Rosenfeld N, Young JW, Alon U, Swain PS, Elowitz MB: Gene Regulation at the Single-Cell Level. Science. 2005, 307 (5717): 1962-1965. 10.1126\/science.1106914","journal-title":"Science"},{"issue":"3","key":"57_CR16","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1049\/ip-syb:20050024","volume":"153","author":"J Kim","year":"2006","unstructured":"Kim J, Bates DG, Postlethwaite I, Ma L, Iglesias PA: Robustness analysis of biochemical network models. IEE Proceedings \u2013 Systems Biology. 2006, 153 (3): 96-104. 10.1049\/ip-syb:20050024","journal-title":"IEE Proceedings \u2013 Systems Biology"},{"issue":"2","key":"57_CR17","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1006\/jtbi.1998.0790","volume":"195","author":"DM Wolf","year":"1998","unstructured":"Wolf DM, Eeckman FH: On the Relationship Between Genomic Regulatory Element Organization and Gene Regulatory Dynamics. Journal of Theoretical Biology. 1998, 195 (2): 167-186. 10.1006\/jtbi.1998.0790","journal-title":"Journal of Theoretical Biology"},{"issue":"27","key":"57_CR18","doi-asserted-by":"publisher","first-page":"9559","DOI":"10.1073\/pnas.0409553102","volume":"102","author":"NE Buchler","year":"2005","unstructured":"Buchler NE, Gerland U, Hwa T: Nonlinear protein degradation and the function of genetic circuits. PNAS. 2005, 102 (27): 9559-9564. 10.1073\/pnas.0409553102","journal-title":"PNAS"},{"issue":"2","key":"57_CR19","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.gde.2005.02.007","volume":"15","author":"L Bintu","year":"2005","unstructured":"Bintu L, Buchler NE, Garcia HG, Gerland U, Hwa T, Kondev J, Phillips R: Transcriptional regulation by the numbers: models. Current Opinion in Genetics & Development. 2005, 15 (2): 116-124. 10.1016\/j.gde.2005.02.007","journal-title":"Current Opinion in Genetics & Development"},{"issue":"2","key":"57_CR20","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.gde.2005.02.006","volume":"15","author":"L Bintu","year":"2005","unstructured":"Bintu L, Buchler NE, Garcia HG, Gerland U, Hwa T, Kondev J, Kuhlman T, Phillips R: Transcriptional regulation by the numbers: applications. Current Opinion in Genetics & Development. 2005, 15 (2): 125-135. 10.1016\/j.gde.2005.02.006","journal-title":"Current Opinion in Genetics & Development"},{"issue":"6","key":"57_CR21","doi-asserted-by":"publisher","first-page":"2943","DOI":"10.1016\/S0006-3495(02)75635-X","volume":"82","author":"M Thattai","year":"2002","unstructured":"Thattai M, van Oudenaarden A: Attenuation of noise in ultrasensitive signaling cascades. Biophysical Journal. 2002, 82 (6): 2943-2950.","journal-title":"Biophysical Journal"},{"issue":"10","key":"57_CR22","doi-asserted-by":"publisher","first-page":"3581","DOI":"10.1073\/pnas.0408507102","volume":"102","author":"S Hooshangi","year":"2005","unstructured":"Hooshangi S, Thiberge S, Weiss R: Ultrasensitivity and noise propagation in a synthetic transcriptional cascade. PNAS. 2005, 102 (10): 3581-3586. 10.1073\/pnas.0408507102","journal-title":"PNAS"},{"issue":"4","key":"57_CR23","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1080\/02681119408806183","volume":"9","author":"E Plahte","year":"1994","unstructured":"Plahte E, Mestl T, Omholt SW: Global Analysis of Steady Points for Systems of Differential-Equations with Sigmoid Interactions. Dynamics and Stability of Systems. 1994, 9 (4): 275-291.","journal-title":"Dynamics and Stability of Systems"},{"issue":"2","key":"57_CR24","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1006\/jtbi.1995.0199","volume":"176","author":"T Mestl","year":"1995","unstructured":"Mestl T, Plahte E, Omholt S: A mathematical framework for describing and analyzing gene regulatory networks. Journal of Theoretical Biology. 1995, 176 (2): 291-300. 10.1006\/jtbi.1995.0199","journal-title":"Journal of Theoretical Biology"},{"issue":"4","key":"57_CR25","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s002850050103","volume":"36","author":"E Plahte","year":"1998","unstructured":"Plahte E, Mestl T, Omholt SW: A methodological basis for description and analysis of systems with complex switch-like interactions. Journal of Mathematical Biology. 1998, 36 (4): 321-348. 10.1007\/s002850050103","journal-title":"Journal of Mathematical Biology"},{"issue":"1\u20132","key":"57_CR26","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.physd.2004.11.014","volume":"201","author":"E Plahte","year":"2005","unstructured":"Plahte E, Kj\u00f8glum S: Analysis and generic properties of gene regulatory networks with graded response functions. Physica D: Nonlinear Phenomena. 2005, 201 (1\u20132): 150-176. 10.1016\/j.physd.2004.11.014.","journal-title":"Physica D: Nonlinear Phenomena"},{"key":"57_CR27","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.biosystems.2006.09.036","volume":"90","author":"SR Veflingstad","year":"2007","unstructured":"Veflingstad SR, Plahte E: Analysis of gene regulatory network models with graded and binary transcriptional responses. Biosystems. 2007, 90: 323-339. 10.1016\/j.biosystems.2006.09.036","journal-title":"Biosystems"},{"key":"57_CR28","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1006\/jtbi.2000.1068","volume":"203","author":"J Cherry","year":"2000","unstructured":"Cherry J, Adler F: How to make a biological switch. Journal of Theoretical Biology. 2000, 203: 117-133. 10.1006\/jtbi.2000.1068","journal-title":"Journal of Theoretical Biology"},{"issue":"11","key":"57_CR29","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/S0167-7799(02)02053-X","volume":"20","author":"P Brazhnik","year":"2002","unstructured":"Brazhnik P, de la Fuente A, Mendes P: Gene networks: how to put the function in genomics. Trends in Biotechnology. 2002, 20 (11): 467-472. 10.1016\/S0167-7799(02)02053-X","journal-title":"Trends in Biotechnology"},{"issue":"6786","key":"57_CR30","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1038\/35014651","volume":"405","author":"A Becskei","year":"2000","unstructured":"Becskei A, Serrano L: Engineering stability in gene networks by autoregulation. Nature. 2000, 405 (6786): 590-593. 10.1038\/35014651","journal-title":"Nature"},{"key":"57_CR31","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/S0022-2836(02)00994-4","volume":"323","author":"N Rosenfeld","year":"2002","unstructured":"Rosenfeld N, Elowitz MB, Alon U: Negative autoregulation speeds the response times of transcription networks. Journal of Molecular Biology. 2002, 323: 785-93. 10.1016\/S0022-2836(02)00994-4","journal-title":"Journal of Molecular Biology"},{"key":"57_CR32","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1089\/10665270252833208","volume":"9","author":"H de Jong","year":"2002","unstructured":"de Jong H: Modeling and Simulation of Genetic Regulatory Systems: A Literature Review. Journal of Computational Biology. 2002, 9: 67-104. 10.1089\/10665270252833208","journal-title":"Journal of Computational Biology"},{"key":"57_CR33","volume-title":"Biological Feedback","author":"R Thomas","year":"1990","unstructured":"Thomas R, D'Ari R: Biological Feedback. 1990, Boca Raton, USA: CRC Press"},{"key":"57_CR34","volume-title":"An Introduction to Systems Biology. Design Principles of Biological Circuits","author":"U Alon","year":"2007","unstructured":"Alon U: An Introduction to Systems Biology. Design Principles of Biological Circuits. 2007, Boca Raton, London, New York: Chapman & Hall (CRC)"},{"issue":"6","key":"57_CR35","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.cell.2004.09.008","volume":"118","author":"J Stelling","year":"2004","unstructured":"Stelling J, Sauer U, Szallasi Z, Doyle FJ, Doyle J: Robustness of Cellular Functions. Cell. 2004, 118 (6): 675-685. 10.1016\/j.cell.2004.09.008","journal-title":"Cell"},{"key":"57_CR36","volume-title":"Robustness and Evolvability in Living Systems","author":"A Wagner","year":"2005","unstructured":"Wagner A: Robustness and Evolvability in Living Systems. 2005, Princeton: Princeton University Press"},{"issue":"11","key":"57_CR37","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/nrg1471","volume":"5","author":"H Kitano","year":"2004","unstructured":"Kitano H: Biological robustness. Nature Reviews Genetics. 2004, 5 (11): 826-837. 10.1038\/nrg1471","journal-title":"Nature Reviews Genetics"},{"issue":"1\u20133","key":"57_CR38","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/S0014-5793(04)00310-2","volume":"563","author":"KV Venkatesh","year":"2004","unstructured":"Venkatesh KV, Bhartiya S, Ruhela A: Multiple feedback loops are key to a robust dynamic performance of tryptophan regulation in Escherichia coli. FEBS Letters. 2004, 563 (1\u20133): 234-240. 10.1016\/S0014-5793(04)00310-2","journal-title":"FEBS Letters"},{"issue":"8","key":"57_CR39","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1098\/rsif.2005.0103","volume":"3","author":"S Bhartiya","year":"2006","unstructured":"Bhartiya S, Chaudhary N, Venkatesh KV, Doyle FJ: Multiple feedback loop design in the tryptophan regulatory network of Escherichia coli suggests a paradigm for robust regulation of processes in series. Journal of the Royal Society Interface. 2006, 3 (8): 383-391. 10.1098\/rsif.2005.0103","journal-title":"Journal of the Royal Society Interface"},{"key":"57_CR40","volume-title":"Molecular Systems Biology","author":"W Ma","year":"2006","unstructured":"Ma W, Lai L, Ouyang Q, Tang C: Robustness and modular design of the Drosophila segment polarity network. Molecular Systems Biology. 2006, 2:"},{"issue":"16","key":"57_CR41","doi-asserted-by":"publisher","first-page":"10528","DOI":"10.1073\/pnas.102303999","volume":"99","author":"ML Siegal","year":"2002","unstructured":"Siegal ML, Bergman A: Waddington's canalization revisited: Developmental stability and evolution. PNAS. 2002, 99 (16): 10528-10532. 10.1073\/pnas.102303999","journal-title":"PNAS"},{"issue":"6792","key":"57_CR42","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/35018085","volume":"406","author":"G von Dassow","year":"2000","unstructured":"von Dassow G, Meir E, Munro E, Odell G: The segment polarity network is a robust development module. Nature. 2000, 406 (6792): 188-192. 10.1038\/35018085","journal-title":"Nature"},{"issue":"6794","key":"57_CR43","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1038\/35019019","volume":"406","author":"R Albert","year":"2000","unstructured":"Albert R, Jeong H, Barabasi AL: Error and attack tolerance of complex networks. Nature. 2000, 406 (6794): 378-382. 10.1038\/35019019","journal-title":"Nature"},{"issue":"6761","key":"57_CR44","doi-asserted-by":"publisher","first-page":"C47","DOI":"10.1038\/35011540","volume":"402","author":"LH Hartwell","year":"1999","unstructured":"Hartwell LH, Hopfield JJ, Leibler S, Murray AW: From molecular to modular cell biology. Nature. 1999, 402 (6761): C47-C52. 10.1038\/35011540","journal-title":"Nature"},{"issue":"10","key":"57_CR45","doi-asserted-by":"publisher","first-page":"5031","DOI":"10.1073\/pnas.97.10.5031","volume":"97","author":"DA Lauffenburger","year":"2000","unstructured":"Lauffenburger DA: Cell signaling pathways as control modules: Complexity for simplicity?. PNAS. 2000, 97 (10): 5031-5033. 10.1073\/pnas.97.10.5031","journal-title":"PNAS"},{"key":"57_CR46","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/msb4100179","volume":"3","author":"H Kitano","year":"2007","unstructured":"Kitano H: Towards a theory of biological robustness. Mol Syst Biol. 2007, 3: 137- 10.1038\/msb4100179","journal-title":"Mol Syst Biol"},{"key":"57_CR47","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1063\/1.1350439","volume":"11","author":"R Thomas","year":"2001","unstructured":"Thomas R, Kaufman M: Multistationarity, the basis of cell differentiation and memory. I. Structural conditions of multistationarity and other nontrivial behavior. Chaos. 2001, 11: 170-179. 10.1063\/1.1350439","journal-title":"Chaos"},{"issue":"4","key":"57_CR48","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1049\/ip-syb:20050101","volume":"153","author":"R Thomas","year":"2006","unstructured":"Thomas R: Circular causality. IEE Proceedings Systems Biology. 2006, 153 (4): 140-153. 10.1049\/ip-syb:20050101","journal-title":"IEE Proceedings Systems Biology"},{"issue":"9","key":"57_CR49","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1038\/nrg1426","volume":"5","author":"G Gibson","year":"2004","unstructured":"Gibson G, Dworkin I: Uncovering cryptic genetic variation. Nat Rev Genet. 2004, 5 (9): 681-90. 10.1038\/nrg1426","journal-title":"Nat Rev Genet"},{"issue":"6948","key":"57_CR50","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/nature01765","volume":"424","author":"A Bergman","year":"2003","unstructured":"Bergman A, Siegal ML: Evolutionary capacitance as a general feature of complex gene networks. Nature. 2003, 424 (6948): 549-552. 10.1038\/nature01765","journal-title":"Nature"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-1-57.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1752-0509-1-57\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-1-57.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T02:03:26Z","timestamp":1630289006000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-1-57"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,12]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2007,12]]}},"alternative-id":["57"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-1-57","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,12]]},"article-number":"57"}}