{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T09:43:21Z","timestamp":1780047801121,"version":"3.53.1"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2005,6,20]],"date-time":"2005-06-20T00:00:00Z","timestamp":1119225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Recent advances in molecular biology techniques provide an opportunity for developing detailed mathematical models of biological processes. An iterative scheme is introduced for model identification using available system knowledge and experimental measurements.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The scheme includes a state regulator algorithm that provides estimates of all system unknowns (concentrations of the system components and the reaction rates of their inter-conversion). The full system information is used for estimation of the model parameters. An optimal experiment design using the parameter identifiability and D-optimality criteria is formulated to provide \"rich\" experimental data for maximizing the accuracy of the parameter estimates in subsequent iterations. The importance of model identifiability tests for optimal measurement selection is also considered. The iterative scheme is tested on a model for the caspase function in apoptosis where it is demonstrated that model accuracy improves with each iteration. Optimal experiment design was determined to be critical for model identification.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The proposed algorithm has general application to modeling a wide range of cellular processes, which include gene regulation networks, signal transduction and metabolic networks.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/1471-2105-6-155","type":"journal-article","created":{"date-parts":[[2005,6,21]],"date-time":"2005-06-21T13:30:13Z","timestamp":1119360613000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["Iterative approach to model identification of biological networks"],"prefix":"10.1186","volume":"6","author":[{"given":"Kapil G","family":"Gadkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudiyanto","family":"Gunawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Francis J","family":"Doyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2005,6,20]]},"reference":[{"key":"480_CR1","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/nature01254","volume":"420","author":"H Kitano","year":"2002","unstructured":"Kitano H: Computational Systems Biology. Nature 2002, 420: 206\u2013210. 10.1038\/nature01254","journal-title":"Nature"},{"issue":"5518","key":"480_CR2","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1126\/science.292.5518.929","volume":"292","author":"T Ideker","year":"2001","unstructured":"Ideker T, Thorsson V, Ranish JA, Christmas R, Buhler J, Eng JK, Bumgarner R, Goodlett DR, Aebersold R, Hood L: Integrated Genomic and Proteomic Analyses of a Systematically Perturbed Network. Science 2001, 292(5518):929\u2013934. 10.1126\/science.292.5518.929","journal-title":"Science"},{"key":"480_CR3","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1002\/bies.10383","volume":"26","author":"H Zhu","year":"2003","unstructured":"Zhu H, Huang S, Dhar P: The Next Step in Systems Biology: Simulating the Temporospatial Dynamics of Molecular Networks. Bioessays 2003, 26: 68\u201372. 10.1002\/bies.10383","journal-title":"Bioessays"},{"key":"480_CR4","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1177\/0037549703040943","volume":"79","author":"KH Cho","year":"2003","unstructured":"Cho KH, Shin SY, Kolch W, Wolkenhauer O: Experimental Design in Systems Biology, Based on Parameter Sensitivity Analysis Using a Monte-Carlo Method: A Case Study for the TNF \u03b1 -Mediated NF- \u03ba B Signal Transduction Pathway. Simulation 2003, 79: 726\u2013739. 10.1177\/0037549703040943","journal-title":"Simulation"},{"key":"480_CR5","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/84379","volume":"19","author":"JS Edwards","year":"2001","unstructured":"Edwards JS, Ibarra RU, Palsson BO: In silico Predictions of Escherichia coli Metabolic Capabilities are Consistent with Experimental Data. Nat Biotechnol 2001, 19: 125\u2013130. 10.1038\/84379","journal-title":"Nat Biotechnol"},{"key":"480_CR6","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1038\/nbt0402-370","volume":"20","author":"B Sch\u00f6berl","year":"2002","unstructured":"Sch\u00f6berl B, Jonsson CE, Gilles ED, M\u00fcller G: Computational Modeling of the Dynamics of the MAP Kinase Cascade Activated by Surface and Internalized EGF Receptors. Nat Biotechnol 2002, 20: 370\u2013375. 10.1038\/nbt0402-370","journal-title":"Nat Biotechnol"},{"key":"480_CR7","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1038\/77589","volume":"18","author":"M Fussenegger","year":"2000","unstructured":"Fussenegger M, Bailey JE, Varner J: A Mathematical Model of Caspase Function in Apoptosis. Nat Biotechnol 2000, 18: 768\u2013774. 10.1038\/81208","journal-title":"Nat Biotechnol"},{"key":"480_CR8","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1091\/mbc.11.1.369","volume":"11","author":"KC Chen","year":"2000","unstructured":"Chen KC, Csikasz-Nagy A, Gyorffy B, Val J, Novak B, Tyson JJ: Kinetic Analysis of a Molecular Model of the Budding Yeast Cell Cycle. Mol Bio Cell 2000, 11: 369\u2013391.","journal-title":"Mol Bio Cell"},{"issue":"3","key":"480_CR9","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1016\/S0006-3495(04)74201-0","volume":"86","author":"XJ Feng","year":"2004","unstructured":"Feng XJ, Rabitz H: Optimal identification of biochemical reaction networks. Biophys J 2004, 86(3):1270\u20131281.","journal-title":"Biophys J"},{"key":"480_CR10","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1101\/gr.1262503","volume":"13","author":"CG Moles","year":"2003","unstructured":"Moles CG, Mendes P, Banga JR: Parameter Estimation in Biochemical Pathways: A Comparison of Global Optimization Methods. Genome Res 2003, 13: 2467\u20132474. 10.1101\/gr.1262503","journal-title":"Genome Res"},{"key":"480_CR11","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1021\/ie990486w","volume":"39","author":"WR Esposito","year":"2000","unstructured":"Esposito WR, Floudas CA: Global Optimization for the Parameter Estimation of Differential-Algebraic Systems. Ind Eng Chem Res 2000, 39: 1291\u20131310. 10.1021\/ie990486w","journal-title":"Ind Eng Chem Res"},{"key":"480_CR12","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-5331-8","volume-title":"Global Optimization in Engineering Design","author":"IE Grossmann","year":"1996","unstructured":"Grossmann IE: Global Optimization in Engineering Design. Dordrecht, Netherlands: Kluwer Academic Publishers; 1996."},{"key":"480_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1023\/A:1016259507911","volume":"24","author":"I Papamichail","year":"2002","unstructured":"Papamichail I, Adjiman CS: A Rigorous Global Optimization Algorithm for Problems with Ordinary Differential Equations. J Global Optim 2002, 24: 1\u201333. 10.1023\/A:1016259507911","journal-title":"J Global Optim"},{"key":"480_CR14","doi-asserted-by":"crossref","unstructured":"Guss C, Boender E, Romeijn HE: Handbook of Global Optimization. Dordrecht, Netherlands: Kluwer Academic Publishers 1995 chap. Stochastic methods; 829\u2013869.","DOI":"10.1007\/978-1-4615-2025-2_15"},{"key":"480_CR15","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1023\/A:1022617804737","volume":"95","author":"MM Ali","year":"1997","unstructured":"Ali MM, Storey C, T\u00f6rn A: Application of Stochastic Global Optimization Algorithms to Practical Problems. J Optim Theory Appl 1997, 95: 545\u2013563. 10.1023\/A:1022617804737","journal-title":"J Optim Theory Appl"},{"key":"480_CR16","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1023\/A:1008395408187","volume":"14","author":"A T\u00f6rn","year":"1999","unstructured":"T\u00f6rn A, Ali MM, Viitanen S: Stochastic Global Optimzation: Problem Classes and Solution Techniques. J Global Optim 1999, 14: 437\u2013447. 10.1023\/A:1008395408187","journal-title":"J Global Optim"},{"key":"480_CR17","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1109\/10.900248","volume":"48","author":"S Audoly","year":"2001","unstructured":"Audoly S, Bellu G, D'Angio L, Saccomani MP, Cobelli C: Global Identifiability of Nonlinear Models of Biological Systems. IEEE Trans Biomed Eng 2001, 48: 55\u201365. 10.1109\/10.900248","journal-title":"IEEE Trans Biomed Eng"},{"key":"480_CR18","first-page":"E727","volume":"258","author":"JA Jacquez","year":"1990","unstructured":"Jacquez JA, Perry T: Parameter estimation: local identifiability of parameters. Amer J Physiol 1990, 258: E727-E736.","journal-title":"Amer J Physiol"},{"key":"480_CR19","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1081\/PRE-120024426","volume":"11","author":"KZ Yao","year":"2003","unstructured":"Yao KZ, Shaw BM, Kou B, McAuley KB, Bacon DW: Modeling Ethylene\/Butene Copolymerization with Multi-Site Catalysts: Parameter Estimability and Experimental Design. Polymer Reaction Eng 2003, 11: 563\u2013588. 10.1081\/PRE-120024426","journal-title":"Polymer Reaction Eng"},{"key":"480_CR20","first-page":"R665","volume":"246","author":"EM Landaw","year":"1984","unstructured":"Landaw EM, DiStefano III JJ: Multiexponential, Multicompartmental, and Noncompartmental Modeling. II. Data Analysis and Statistical Considerations. Amer J Physiol 1984, 246: R665-R677.","journal-title":"Amer J Physiol"},{"key":"480_CR21","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2166\/wst.2001.0444","volume":"43","author":"B Petersen","year":"2001","unstructured":"Petersen B, Gernaey K, Vanrolleghem PA: Practical Identifiability of Model Parameters by Combined Respirometric-Titrimetric Measurements. Water Science Tech 2001, 43: 347\u2013355.","journal-title":"Water Science Tech"},{"key":"480_CR22","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1101\/gr.1198103","volume":"13","author":"DE Zak","year":"2003","unstructured":"Zak DE, Gonye GE, Schwaber J, Doyle III FJ: Importance of Input Perturbations and Stochastic Gene Expression in the Reverse Engineering of Genetic Regulatory Networks: Insights from an Identifiability Analysis of an in Silico Network. Genome Res 2003, 13: 2396\u20132405. 10.1101\/gr.1198103","journal-title":"Genome Res"},{"key":"480_CR23","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1016\/S0098-1354(00)00328-8","volume":"24","author":"SP Asprey","year":"2000","unstructured":"Asprey SP, Macchietto S: Statistical Tools for Optimal Dynamic Model Building. Comput Chem Eng 2000, 24: 1261\u20131267. 10.1016\/S0098-1354(00)00328-8","journal-title":"Comput Chem Eng"},{"key":"480_CR24","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1101\/gr.1226004","volume":"14","author":"A Kremling","year":"2004","unstructured":"Kremling A, Fischer S, Gadkar K, Doyle III FJ, Sauter T, Bullinger E, Allgower F, Gilles ED: A Benchmark for Methods in Reverse Engineering and Model Discrimination: Problem Formulation and Solutions. Genome Res 2004, 14: 1773\u20131785. 10.1101\/gr.1226004","journal-title":"Genome Res"},{"key":"480_CR25","doi-asserted-by":"publisher","first-page":"2425","DOI":"10.1021\/ie010183d","volume":"41","author":"JR Banga","year":"2002","unstructured":"Banga JR, Versyck KJ, Impe JFV: Computation of Optimal Identification Experiments for Nonlinear Dynamic Process Models: A Stochastic Global Optimization Approach. Ind Eng Chem Res 2002, 41: 2425\u20132430. 10.1021\/ie010183d","journal-title":"Ind Eng Chem Res"},{"key":"480_CR26","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1016\/S0006-3495(02)73903-9","volume":"83","author":"R Mahadevan","year":"2002","unstructured":"Mahadevan R, Edwards JS, Doyle III FJ: Dynamic Flux Balance Analysis of Diauxic Growth in. E coli Biophys J 2002, 83: 1331\u20131340.","journal-title":"E coli Biophys J"},{"key":"480_CR27","doi-asserted-by":"publisher","DOI":"10.1002\/047134608X.W1046","volume-title":"System Identification: Theory for the User","author":"L Ljung","year":"1999","unstructured":"Ljung L: System Identification: Theory for the User. Englewood Cliffs, NJ: Prentice Hall; 1999."},{"key":"480_CR28","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1109\/9.623084","volume":"42","author":"L Ljung","year":"1997","unstructured":"Ljung L, Guo L: The Role of Model Validation for Assessing the Size of the Unmodeled Dynamics. IEEE Trans Automat Contr 1997, 42: 1230\u20131239. 10.1109\/9.623084","journal-title":"IEEE Trans Automat Contr"},{"key":"480_CR29","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1109\/9.284871","volume":"39","author":"K Poolla","year":"1994","unstructured":"Poolla K, Khargonekar P, Tikku A, Krause J, Nagpal K: A Time-Domain Approach to Model Validation. IEEE Trans Automat Contr 1994, 39: 951\u2013959. 10.1109\/9.284871","journal-title":"IEEE Trans Automat Contr"},{"key":"480_CR30","volume-title":"Modern Control Theory","author":"WL Brogan","year":"1991","unstructured":"Brogan WL: Modern Control Theory. Upper Saddle River, NJ: Prentice Hall; 1991."},{"key":"480_CR31","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1080\/00986448908940662","volume":"83","author":"S Vajda","year":"1989","unstructured":"Vajda S, Rabitz H, Walter E, Lecourtier Y: Qualitative and Quantitative Indentifiability Analysis of Non-Linear Chemical Kinetic Models. Chem Eng Commun 1989, 83: 191\u2013219.","journal-title":"Chem Eng Commun"},{"key":"480_CR32","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1088\/0957-0233\/9\/6\/003","volume":"9","author":"AF Emery","year":"1998","unstructured":"Emery AF, Nenarokomov AV: Optimal Experimental Design. Meas Sci Technol 1998, 9: 864\u2013876. 10.1088\/0957-0233\/9\/6\/003","journal-title":"Meas Sci Technol"},{"key":"480_CR33","volume-title":"Parameter Estimation in Engineering and Science","author":"JV Beck","year":"1977","unstructured":"Beck JV, Arnold KJ: Parameter Estimation in Engineering and Science. Toronto, Canada: John Wiley & Sons; 1977."},{"key":"480_CR34","volume-title":"Int Conf Systems Biology, Heidelberg, Germany","author":"KG Gadkar","year":"2004","unstructured":"Gadkar KG, Gunawan R, Doyle III FJ: Heuristic Methods for Measurement Selection for Identification of Biological Systems. Int Conf Systems Biology, Heidelberg, Germany 2004."},{"key":"480_CR35","volume-title":"On-Line Estimation and Adaptive Control of Bioreactors","author":"G Bastin","year":"1990","unstructured":"Bastin G, Dochain D: On-Line Estimation and Adaptive Control of Bioreactors. Amsterdam: Elsevier; 1990."},{"key":"480_CR36","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1021\/bp00020a009","volume":"9","author":"J Albiol","year":"1993","unstructured":"Albiol J, Robust\u00e9 J, Casas C, Poch M: Biomass Estimation in Plant Cell Cultures Using Extended Kalman Filter. Biotechnol Prog 1993, 9: 174\u2013178. 10.1021\/bp00020a009","journal-title":"Biotechnol Prog"},{"key":"480_CR37","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1021\/bp950049m","volume":"12","author":"DA Gee","year":"1996","unstructured":"Gee DA, Ramirez WF: On-Line State Estimation and Parameter Identification for Batch Fermentation. Biotechnol Prog 1996, 12: 132\u2013140. 10.1021\/bp950049m","journal-title":"Biotechnol Prog"},{"key":"480_CR38","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1002\/bit.260261006","volume":"26","author":"G Stephanopoulos","year":"1984","unstructured":"Stephanopoulos G, San KY: Studies on on-Line Biorector Identification. I. Theory. Biotechnol Bioeng 1984, 26: 1176\u20131188. 10.1002\/bit.260261006","journal-title":"Biotechnol Bioeng"},{"key":"480_CR39","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/S0168-1656(96)01645-8","volume":"52","author":"J Glassey","year":"1997","unstructured":"Glassey J, Ignova M, Ward AC, Montague GA, Morris AJ: Bioprocess Supervision: Neural Networks and Knowledge Based Systems. J Biotechnol 1997, 52: 201\u2013205. 10.1016\/S0168-1656(96)01645-8","journal-title":"J Biotechnol"},{"issue":"Suppl","key":"480_CR40","doi-asserted-by":"publisher","first-page":"S369","DOI":"10.1016\/S0098-1354(09)80044-6","volume":"16","author":"MN Karim","year":"1992","unstructured":"Karim MN, Rivera SL: Comparision of Feed-Forward and Recurrent Neural Networks for Bioprocess State Estimation. Comp Chem Eng 1992, 16(Suppl):S369-S377.","journal-title":"Comp Chem Eng"},{"key":"480_CR41","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1021\/bp9700364","volume":"13","author":"R Simutis","year":"1997","unstructured":"Simutis R, L\u00fcbbert A: Exploratory Analysis of Bioprocesses Using Artificial Neural Network-Based Methods. Biotechnol Prog 1997, 13: 479\u2013487. 10.1021\/bp9700364","journal-title":"Biotechnol Prog"},{"key":"480_CR42","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1002\/aic.690490819","volume":"49","author":"R Gunawan","year":"2003","unstructured":"Gunawan R, Jung MYL, Seebauer EG, Braatz RD: Maximum a Posteriori Estimation of Transient Enhanced Diffusion Energetics. AIChE J 2003, 49: 2114\u20132123. 10.1002\/aic.690490819","journal-title":"AIChE J"},{"key":"480_CR43","doi-asserted-by":"publisher","DOI":"10.1002\/0471200611","volume-title":"Elements of Information Theory","author":"TM Cover","year":"1991","unstructured":"Cover TM, Thomas JA: Elements of Information Theory. John Wiley & Sons; 1991."},{"key":"480_CR44","volume-title":"IEE Systems Biology","author":"KG Gadkar","year":"2005","unstructured":"Gadkar KG, Varner J, Doyle III FJ: Model Identification of Signal Transduction Networks from Data Using a State Regulator Problem. IEE Systems Biology 2005., 2:"},{"issue":"12","key":"480_CR45","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1093\/bioinformatics\/17.12.1183","volume":"17","author":"A Wagner","year":"2001","unstructured":"Wagner A: How to reconstruct a large genetic network from n gene perturbations in fewer than n2easy steps. Bioinformatics 2001, 17(12):1183\u20131197. 10.1093\/bioinformatics\/17.12.1183","journal-title":"Bioinformatics"},{"key":"480_CR46","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1126\/science.1081900","volume":"301","author":"TS Gardner","year":"2003","unstructured":"Gardner TS, Bernardo DD, Lorenz D, Collins JJ: Inferring genetic networks and identifying compound model of action via expression profiling. Science 2003, 301: 102\u2013105. 10.1126\/science.1081900","journal-title":"Science"},{"issue":"4","key":"480_CR47","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1038\/ng1532","volume":"37","author":"K Basso","year":"2005","unstructured":"Basso K, Margolin AA, Stolovitzky G, Klein U, Dalla-Favera R, Califano A: Reverse engineering of regulatory networks in human B cells. Nat Genet 2005, 37(4):382\u2013390. [http:\/\/dx.doi.org\/10.1038\/ng1532] 10.1038\/ng1532","journal-title":"Nat Genet"},{"key":"480_CR48","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1021\/ie0203025","volume":"42","author":"BH Chen","year":"2003","unstructured":"Chen BH, Asprey SP: On the Design of Optimally Informative Deynamic Experiments for Model Discrimination in Multiresponse Nonlinear Situations. Ind Eng Chem Res 2003, 42: 1379\u20131390. 10.1021\/ie0203025","journal-title":"Ind Eng Chem Res"},{"key":"480_CR49","volume-title":"Biotechnol Bioeng","author":"AD Frey","year":"2005","unstructured":"Frey AD, Kallio PT, Gadkar KG, Varner J: Dynamic Flux Balance Analysis of VHb Expression in Escherichia coli MG1655. Biotechnol Bioeng 2005. accepted"},{"key":"480_CR50","volume-title":"BioSens 2.0: Sensitivity Analysis Toolkit","author":"S Taylor","year":"2005","unstructured":"Taylor S, Gunawan R, Doyle III FJ: BioSens 2.0: Sensitivity Analysis Toolkit.2005. [http:\/\/www.chemengr.ucsb.edu\/~ceweb\/faculty\/doyle\/biosens\/BioSens.htm]"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-6-155.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1471-2105-6-155\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-6-155.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T17:55:39Z","timestamp":1706810139000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-6-155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,6,20]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2005,12]]}},"alternative-id":["480"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-6-155","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,6,20]]},"assertion":[{"value":"3 February 2005","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2005","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2005","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"155"}}