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In this case, more than one molecular mechanism can explain available data. In order to rule out the incorrect mechanisms, one needs to invalidate incorrect models. At this point, new experiments maximizing the difference between the measured values of alternative models should be proposed and conducted. Such experiments should be optimally designed to produce data that are most likely to invalidate incorrect model structures.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In this paper we develop methodologies for the optimal design of experiments with the aim of discriminating between different mathematical models of the same biological system. The first approach determines the 'best' initial condition that maximizes the <jats:italic>L<\/jats:italic>\n              <jats:sub>2<\/jats:sub> (energy) distance between the outputs of the rival models. In the second approach, we maximize the <jats:italic>L<\/jats:italic>\n              <jats:sub>2<\/jats:sub>-distance of the outputs by designing the optimal external stimulus (input) profile of unit <jats:italic>L<\/jats:italic>\n              <jats:sub>2<\/jats:sub>-norm. Our third method uses optimized structural changes (corresponding, for example, to parameter value changes reflecting gene knock-outs) to achieve the same goal. The numerical implementation of each method is considered in an example, signal processing in starving <jats:italic>Dictyostelium<\/jats:italic> am\u0153b\u00e6.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Model-based design of experiments improves both the reliability and the efficiency of biochemical network model discrimination. This opens the way to model invalidation, which can be used to perfect our understanding of biochemical networks. Our general problem formulation together with the three proposed experiment design methods give the practitioner new tools for a systems biology approach to experiment design.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-4-38","type":"journal-article","created":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T06:13:43Z","timestamp":1270102423000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Discriminating between rival biochemical network models: three approaches to optimal experiment design"],"prefix":"10.1186","volume":"4","author":[{"given":"Bence","family":"M\u00e9lyk\u00fati","sequence":"first","affiliation":[]},{"given":"Elias","family":"August","sequence":"additional","affiliation":[]},{"given":"Antonis","family":"Papachristodoulou","sequence":"additional","affiliation":[]},{"given":"Hana","family":"El-Samad","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,4,1]]},"reference":[{"key":"427_CR1","doi-asserted-by":"crossref","DOI":"10.1007\/b98869","volume-title":"Mathematical biology","author":"JD Murray","year":"2003","unstructured":"Murray JD: Mathematical biology. 2003, 1-2: Springer-Verlag, New York,"},{"key":"427_CR2","volume-title":"System modeling in cellular biology: from concepts to nuts and bolts","year":"2006","unstructured":"Szallasi Z, Stelling J, Periwal V, : System modeling in cellular biology: from concepts to nuts and bolts. 2006, MIT Press, Cambridge,"},{"key":"427_CR3","volume-title":"Fundamentals of enzyme kinetics","author":"A Cornish-Bowden","year":"2004","unstructured":"Cornish-Bowden A: Fundamentals of enzyme kinetics. 2004, Portland Press, London,"},{"key":"427_CR4","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4613-1161-4","volume-title":"The regulation of cellular systems","author":"R Heinrich","year":"1996","unstructured":"Heinrich R, Schuster S: The regulation of cellular systems. 1996, Chapman & Hall, New York,"},{"key":"427_CR5","volume-title":"Understanding the control of metabolism","author":"D Fell","year":"1997","unstructured":"Fell D: Understanding the control of metabolism. 1997, Portland Press, London,"},{"key":"427_CR6","volume-title":"Computational modeling of genetic and biochemical networks","year":"2004","unstructured":"Bower JM, Bolouri H, : Computational modeling of genetic and biochemical networks. 2004, MIT Press, Cambridge,"},{"issue":"5","key":"427_CR7","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1371\/journal.pcbi.0020052","volume":"2","author":"CL Barrett","year":"2006","unstructured":"Barrett CL, Palsson BO: Iterative Reconstruction of Transcriptional Regulatory Networks: An Algorithmic Approach. 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