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Unfortunately, the associated computational requirement often becomes prohibitively high due to the large number of parameters and the lack of complete parameter identifiability (i.e. not all parameters can be uniquely identified).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In this work, an incremental approach was applied to the parameter estimation of ODE models from concentration time profiles. Particularly, the method was developed to address a commonly encountered circumstance in the modeling of metabolic networks, where the number of metabolic fluxes (reaction rates) exceeds that of metabolites (chemical species). Here, the minimization of model residuals was performed over a subset of the parameter space that is associated with the degrees of freedom in the dynamic flux estimation from the concentration time-slopes. The efficacy of this method was demonstrated using two generalized mass action (GMA) models, where the method significantly outperformed single-step estimations. In addition, an extension of the estimation method to handle missing data is also presented.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The proposed incremental estimation method is able to tackle the issue on the lack of complete parameter identifiability and to significantly reduce the computational efforts in estimating model parameters, which will facilitate kinetic modeling of genome-scale cellular metabolism in the future.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-6-142","type":"journal-article","created":{"date-parts":[[2012,11,21]],"date-time":"2012-11-21T11:14:26Z","timestamp":1353496466000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Incremental parameter estimation of kinetic metabolic network models"],"prefix":"10.1186","volume":"6","author":[{"given":"Gengjie","family":"Jia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Stephanopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudiyanto","family":"Gunawan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,11,21]]},"reference":[{"issue":"2","key":"1041_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.mbs.2009.03.002","volume":"219","author":"IC Chou","year":"2009","unstructured":"Chou IC, Voit EO: Recent developments in parameter estimation and structure identification of biochemical and genomic systems. 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