{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:12:39Z","timestamp":1783591959875,"version":"3.55.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2011,3,15]],"date-time":"2011-03-15T00:00:00Z","timestamp":1300147200000},"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":[[2011,12]]},"DOI":"10.1186\/1752-0509-5-41","type":"journal-article","created":{"date-parts":[[2011,3,16]],"date-time":"2011-03-16T15:22:27Z","timestamp":1300288947000},"source":"Crossref","is-referenced-by-count":32,"title":["Understanding dynamics using sensitivity analysis: caveat and solution"],"prefix":"10.1186","volume":"5","author":[{"given":"Thanneer M","family":"Perumal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudiyanto","family":"Gunawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,3,15]]},"reference":[{"key":"632_CR1","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1049\/iet-syb:20060053","volume":"1","author":"Y Chu","year":"2007","unstructured":"Chu Y, Jayaraman A, Hahn J: Parameter sensitivity analysis of IL-6 signalling pathways. IET Syst Biol 2007, 1: 342-352. 10.1049\/iet-syb:20060053","journal-title":"IET Syst Biol"},{"key":"632_CR2","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1049\/sb:20045009","volume":"1","author":"AE Ihekwaba","year":"2004","unstructured":"Ihekwaba AE, Broomhead DS, Grimley RL, Benson N, Kell DB: Sensitivity analysis of parameters controlling oscillatory signalling in the NF-kappaB pathway: the roles of IKK and IkappaBalpha. Syst Biol (Stevenage) 2004, 1: 93-103. 10.1049\/sb:20045009","journal-title":"Syst Biol (Stevenage)"},{"key":"632_CR3","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1049\/ip-syb:20050050","volume":"152","author":"AE Ihekwaba","year":"2005","unstructured":"Ihekwaba AE, Broomhead DS, Grimley R, Benson N, White MR, Kell DB: Synergistic control of oscillations in the NF-kappaB signalling pathway. Syst Biol (Stevenage) 2005, 152: 153-160.","journal-title":"Syst Biol (Stevenage)"},{"key":"632_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1749-6632.2008.03747.x","volume":"1158","author":"P Adler","year":"2009","unstructured":"Adler P, Peterson H, Agius P, Reimand J, Vilo J: Ranking Genes by Their Co-expression to Subsets of Pathway Members. Annals of the New York Academy of Sciences 2009, 1158: 1-13. 10.1111\/j.1749-6632.2008.03747.x","journal-title":"Annals of the New York Academy of Sciences"},{"key":"632_CR5","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.biosystems.2008.05.016","volume":"94","author":"K Iwamoto","year":"2008","unstructured":"Iwamoto K, Tashima Y, Hamada H, Eguchi Y, Okamoto M: Mathematical modeling and sensitivity analysis of G1\/S phase in the cell cycle including the DNA-damage signal transduction pathway. Biosystems 2008, 94: 109-117. 10.1016\/j.biosystems.2008.05.016","journal-title":"Biosystems"},{"key":"632_CR6","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1002\/kin.20366","volume":"40","author":"A Lovrics","year":"2008","unstructured":"Lovrics A, Zs\u00e9ly GyI, Csik\u00e1sz-Nagy A, Z\u00e1dor J, Tur\u00e1nyi T, Nov\u00e1k B: Analysis of a budding yeast cell cycle model using the shapes of local sensitivity functions. International Journal of Chemical Kinetics 2008, 40: 710-720. 10.1002\/kin.20366","journal-title":"International Journal of Chemical Kinetics"},{"key":"632_CR7","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1016\/j.compchemeng.2007.10.013","volume":"32","author":"Y Jin","year":"2008","unstructured":"Jin Y, Peng X, Liang Y, Ma J: Uniform design-based sensitivity analysis of circadian rhythm model in Neurospora. Computers and Chemical Engineering 2008, 32: 1956-1962. 10.1016\/j.compchemeng.2007.10.013","journal-title":"Computers and Chemical Engineering"},{"key":"632_CR8","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.bpj.2009.04.053","volume":"97","author":"T Zhang","year":"2009","unstructured":"Zhang T, Brazhnik P, Tyson JJ: Computational analysis of dynamical responses to the intrinsic pathway of programmed cell death. Biophys J 2009, 97: 415-434. 10.1016\/j.bpj.2009.04.053","journal-title":"Biophys J"},{"key":"632_CR9","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1371\/journal.pcbi.0040001","volume":"4","author":"CH Hansen","year":"2008","unstructured":"Hansen CH, Endres RG, Wingreen NS: Chemotaxis in Escherichia coli: a molecular model for robust precise adaptation. PLoS Comput Biol 2008, 4: e1. 10.1371\/journal.pcbi.0040001","journal-title":"PLoS Comput Biol"},{"key":"632_CR10","unstructured":"MATLAB \n                    http:\/\/www.mathworks.com\/"},{"key":"632_CR11","unstructured":"XPPAUT \n                    http:\/\/www.math.pitt.edu\/~bard\/xpp\/xpp.html"},{"key":"632_CR12","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1093\/bioinformatics\/bti799","volume":"22","author":"H Schmidt","year":"2006","unstructured":"Schmidt H, Jirstrand M: Systems Biology Toolbox for MATLAB: a computational platform for research in systems biology. Bioinformatics 2006, 22: 514-515. 10.1093\/bioinformatics\/bti799","journal-title":"Bioinformatics"},{"key":"632_CR13","doi-asserted-by":"publisher","first-page":"2037","DOI":"10.1093\/bioinformatics\/btn350","volume":"24","author":"T Maiwald","year":"2008","unstructured":"Maiwald T, Timmer J: Dynamical modeling and multi-experiment fitting with PottersWheel. Bioinformatics 2008, 24: 2037-2043. 10.1093\/bioinformatics\/btn350","journal-title":"Bioinformatics"},{"key":"632_CR14","first-page":"563","volume":"9","author":"P Mendes","year":"1993","unstructured":"Mendes P: GEPASI: a software package for modelling the dynamics, steady states and control of biochemical and other systems. Comput Appl Biosci 1993, 9: 563-571.","journal-title":"Comput Appl Biosci"},{"key":"632_CR15","doi-asserted-by":"publisher","first-page":"3067","DOI":"10.1093\/bioinformatics\/btl485","volume":"22","author":"S Hoops","year":"2006","unstructured":"Hoops S, Sahle S, Gauges R, Lee C, Pahle J, Simus N, Singhal M, Xu L, Mendes P, Kummer U: COPASI--a COmplex PAthway SImulator. Bioinformatics 2006, 22: 3067-3074. 10.1093\/bioinformatics\/btl485","journal-title":"Bioinformatics"},{"key":"632_CR16","unstructured":"JDesigner\/Jarnac \n                    http:\/\/sbw.kgi.edu\/"},{"key":"632_CR17","unstructured":"JSim \n                    http:\/\/www.physiome.org\/jsim\/"},{"key":"632_CR18","unstructured":"BioSens \n                    http:\/\/www.chemengr.ucsb.edu\/~ceweb\/faculty\/doyle\/biosens\/BioSens.htm"},{"key":"632_CR19","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1186\/1471-2105-9-342","volume":"9","author":"Z Zi","year":"2008","unstructured":"Zi Z, Zheng Y, Rundell AE, Klipp E: SBML-SAT: a systems biology markup language (SBML) based sensitivity analysis tool. BMC Bioinformatics 2008, 9: 342. 10.1186\/1471-2105-9-342","journal-title":"BMC Bioinformatics"},{"key":"632_CR20","doi-asserted-by":"crossref","unstructured":"Rodriguez-Fernandez M, Banga JR: SensSB: a software toolbox for the development and sensitivity analysis of systems biology models. Bioinformatics 26: 1675-1676. 10.1093\/bioinformatics\/btq242","DOI":"10.1093\/bioinformatics\/btq242"},{"key":"632_CR21","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nbt0606-667","volume":"24","author":"R Alves","year":"2006","unstructured":"Alves R, Antunes F, Salvador A: Tools for kinetic modeling of biochemical networks. Nat Biotechnol 2006, 24: 667-672. 10.1038\/nbt0606-667","journal-title":"Nat Biotechnol"},{"key":"632_CR22","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/nbt0407-390","volume":"25","author":"E Klipp","year":"2007","unstructured":"Klipp E, Liebermeister W, Helbig A, Kowald A, Schaber J: Systems biology standards--the community speaks. Nat Biotechnol 2007, 25: 390-391. 10.1038\/nbt0407-390","journal-title":"Nat Biotechnol"},{"key":"632_CR23","volume-title":"Sensitivity Analysis: Gauging the Worth of Scientific Models","author":"A Saltelli","year":"2000","unstructured":"Saltelli A, Chan K, Scott EM: Sensitivity Analysis: Gauging the Worth of Scientific Models. John Wiley \\& Sons, Ltd.; 2000."},{"key":"632_CR24","doi-asserted-by":"publisher","first-page":"2811","DOI":"10.1021\/cr040659d","volume":"105","author":"A Saltelli","year":"2005","unstructured":"Saltelli A, Ratto M, Tarantola S, Campolongo F: Sensitivity analysis for chemical models. Chem Rev 2005, 105: 2811-2827. 10.1021\/cr040659d","journal-title":"Chem Rev"},{"key":"632_CR25","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1214\/ss\/1009213004","volume":"15","author":"A Saltelli","year":"2000","unstructured":"Saltelli A, Tarantola S, Campolongo F: Sensitivity Analysis as an Ingredient of Modeling. Stat Sci 2000, 15: 377-395. 10.1214\/ss\/1009213004","journal-title":"Stat Sci"},{"key":"632_CR26","volume-title":"Sensitivity Analysis in Practice: A Guide to Assessing Scientific Models","author":"A Saltelli","year":"2004","unstructured":"Saltelli A, Tarantola S, Campolongo F, Ratto M: Sensitivity Analysis in Practice: A Guide to Assessing Scientific Models. John Wiley \\& Sons, Ltd.; 2004."},{"key":"632_CR27","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/BF01166355","volume":"5","author":"T Tur\u00e1nyi","year":"1990","unstructured":"Tur\u00e1nyi T: Sensitivity analysis of complex kinetic systems. Tools and applications. Journal of Mathematical Chemistry 1990, 5: 203-248.","journal-title":"Journal of Mathematical Chemistry"},{"key":"632_CR28","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511721779","volume-title":"Parametirc Sensitivity in Chemical Systems","author":"A Varma","year":"1999","unstructured":"Varma A, Morbidelli M, Wu H: Parametirc Sensitivity in Chemical Systems. Cambridge University Press, Cambridge, UK; 1999."},{"key":"632_CR29","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1111\/0272-4332.00039","volume":"22","author":"HC Frey","year":"2002","unstructured":"Frey HC, Patil SR: Identification and review of sensitivity analysis methods. Risk Anal 2002, 22: 553-578. 10.1111\/0272-4332.00039","journal-title":"Risk Anal"},{"key":"632_CR30","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1042\/bse0450177","volume":"45","author":"B Ingalls","year":"2008","unstructured":"Ingalls B: Sensitivity analysis: from model parameters to system behaviour. Essays Biochem 2008, 45: 177-193. 10.1042\/BSE0450177","journal-title":"Essays Biochem"},{"key":"632_CR31","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.jtbi.2008.04.011","volume":"254","author":"S Marino","year":"2008","unstructured":"Marino S, Hogue IB, Ray CJ, Kirschner DE: A methodology for performing global uncertainty and sensitivity analysis in systems biology. J Theor Biol 2008, 254: 178-196. 10.1016\/j.jtbi.2008.04.011","journal-title":"J Theor Biol"},{"key":"632_CR32","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1146\/annurev.pc.34.100183.002223","volume":"34","author":"H Rabitz","year":"1983","unstructured":"Rabitz H, Kramer M, Dacol D: Sensitivity analysis in chemical kinetics. Annual review of Physical Chemistry 1983, 34: 419-461. 10.1146\/annurev.pc.34.100183.002223","journal-title":"Annual review of Physical Chemistry"},{"key":"632_CR33","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.cell.2004.09.008","volume":"118","author":"Stelling Jr","year":"2004","unstructured":"Stelling Jr, Sauer U, Szallasi Z, Doyle FJ, Doyle J: Robustness of cellular functions. Cell 2004, 118: 675-685. 10.1016\/j.cell.2004.09.008","journal-title":"Cell"},{"key":"632_CR34","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1083\/jcb.200404158","volume":"166","author":"M Bentele","year":"2004","unstructured":"Bentele M, Lavrik I, Ulrich M, Stober S, Heermann DW, Kalthoff H, Krammer PH, Eils R: Mathematical modeling reveals threshold mechanism in CD95-induced apoptosis. J Cell Biol 2004, 166: 839-851. 10.1083\/jcb.200404158","journal-title":"J Cell Biol"},{"key":"632_CR35","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1049\/ip-syb:20050046","volume":"152","author":"T Eissing","year":"2005","unstructured":"Eissing T, Allgower F, Bullinger E: Robustness properties of apoptosis models with respect to parameter variations and intrinsic noise. Syst Biol (Stevenage) 2005, 152: 221-228.","journal-title":"Syst Biol (Stevenage)"},{"key":"632_CR36","doi-asserted-by":"publisher","first-page":"985","DOI":"10.4049\/jimmunol.175.2.985","volume":"175","author":"F Hua","year":"2005","unstructured":"Hua F, Cornejo MG, Cardone MH, Stokes CL, Lauffenburger DA: Effects of Bcl-2 levels on Fas signaling-induced caspase-3 activation: molecular genetic tests of computational model predictions. J Immunol 2005, 175: 985-995.","journal-title":"J Immunol"},{"key":"632_CR37","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1098\/rsif.2005.0109","volume":"3","author":"F Hua","year":"2006","unstructured":"Hua F, Hautaniemi S, Yokoo R, Lauffenburger DA: Integrated mechanistic and data-driven modelling for multivariate analysis of signalling pathways. J R Soc Interface 2006, 3: 515-526. 10.1098\/rsif.2005.0109","journal-title":"J R Soc Interface"},{"key":"632_CR38","volume-title":"Biophys J","author":"JE Shoemaker","year":"2008","unstructured":"Shoemaker JE, Doyle III FJ: Identifying Fragilities in Biochemical Networks: Robust Performance Analysis of Fas Signaling-Induced Apoptosis. Biophys J 2008."},{"key":"632_CR39","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1049\/ip-syb:20050065","volume":"153","author":"BB Aldridge","year":"2006","unstructured":"Aldridge BB, Haller G, Sorger PK, Lauffenburger DA: Direct Lyapunov exponent analysis enables parametric study of transient signalling governing cell behaviour. Syst Biol (Stevenage) 2006, 153: 425-432.","journal-title":"Syst Biol (Stevenage)"},{"key":"632_CR40","doi-asserted-by":"publisher","first-page":"13210","DOI":"10.1073\/pnas.0401463101","volume":"101","author":"Stelling Jr","year":"2004","unstructured":"Stelling Jr, Gilles ED, Doyle FJ: Robustness properties of circadian clock architectures. Proc Natl Acad Sci USA 2004, 101: 13210-13215. 10.1073\/pnas.0401463101","journal-title":"Proc Natl Acad Sci USA"},{"key":"632_CR41","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1177\/0748730407299194","volume":"22","author":"R Gunawan","year":"2007","unstructured":"Gunawan R, Doyle FJ: Phase sensitivity analysis of circadian rhythm entrainment. J Biol Rhythms 2007, 22: 180-194. 10.1177\/0748730407299194","journal-title":"J Biol Rhythms"},{"key":"632_CR42","doi-asserted-by":"publisher","first-page":"5361","DOI":"10.1021\/jp0561975","volume":"110","author":"D Hu","year":"2006","unstructured":"Hu D, Yuan JM: Time-dependent sensitivity analysis of biological networks: coupled MAPK and PI3K signal transduction pathways. J Phys Chem A 2006, 110: 5361-5370. 10.1021\/jp0561975","journal-title":"J Phys Chem A"},{"key":"632_CR43","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1002\/kin.20369","volume":"40","author":"H Yue","year":"2008","unstructured":"Yue H, Brown M, He F, Jia J, Kell DB: Sensitivity analysis and robust experimental design of a signal transduction pathway system. International Journal of Chemical Kinetics 2008, 40: 730-741. 10.1002\/kin.20369","journal-title":"International Journal of Chemical Kinetics"},{"key":"632_CR44","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1039\/b609442b","volume":"2","author":"H Yue","year":"2006","unstructured":"Yue H, Brown M, Knowles J, Wang H, Broomhead DS, Kell DB: Insights into the behaviour of systems biology models from dynamic sensitivity and identifiability analysis: a case study of an NF-kappaB signalling pathway. Mol Biosyst 2006, 2: 640-649. 10.1039\/b609442b","journal-title":"Mol Biosyst"},{"key":"632_CR45","volume-title":"Global sensitivity analysis: the primer","author":"A Saltelli","year":"2008","unstructured":"Saltelli A: Global sensitivity analysis: the primer. Chichester, England: John Wiley; 2008."},{"key":"632_CR46","first-page":"re9","volume-title":"Sci STKE 2004","author":"JC Reed","year":"2004","unstructured":"Reed JC, Doctor KS, Godzik A: The domains of apoptosis: a genomics perspective. Sci STKE 2004 2004, re9. 10.1126\/stke.2392004re9"},{"key":"632_CR47","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.jtbi.2009.07.037","volume":"261","author":"TM Perumal","year":"2009","unstructured":"Perumal TM, Wu Y, Gunawan R: Dynamical analysis of cellular networks based on the Green's function matrix. J Theor Biol 2009, 261: 248-259. 10.1016\/j.jtbi.2009.07.037","journal-title":"J Theor Biol"},{"key":"632_CR48","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.jtbi.2007.10.030","volume":"250","author":"N Okazaki","year":"2008","unstructured":"Okazaki N, Asano R, Kinoshita T, Chuman H: Simple computational models of type I\/type II cells in Fas signaling-induced apoptosis. J Theor Biol 2008, 250: 621-633. 10.1016\/j.jtbi.2007.10.030","journal-title":"J Theor Biol"},{"key":"632_CR49","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/S0014-5793(02)03842-5","volume":"534","author":"S Yamada","year":"2003","unstructured":"Yamada S, Shiono S, Joo A, Yoshimura A: Control mechanism of JAK\/STAT signal transduction pathway. FEBS Lett 2003, 534: 190-196. 10.1016\/S0014-5793(02)03842-5","journal-title":"FEBS Lett"},{"key":"632_CR50","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1016\/j.febslet.2005.01.009","volume":"579","author":"Z Zi","year":"2005","unstructured":"Zi Z, Cho KH, Sung MH, Xia X, Zheng J, Sun Z: In silico identification of the key components and steps in IFN-gamma induced JAK-STAT signaling pathway. FEBS Lett 2005, 579: 1101-1108. 10.1016\/j.febslet.2005.01.009","journal-title":"FEBS Lett"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-5-41.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1752-0509-5-41\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1752-0509-5-41.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,1,22]],"date-time":"2019-01-22T21:38:44Z","timestamp":1548193124000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/1752-0509-5-41"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,3,15]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["632"],"URL":"https:\/\/doi.org\/10.1186\/1752-0509-5-41","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,3,15]]},"article-number":"41"}}