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Equilibrium model selection: dTTP induced R1 dimerization

BACKGROUND: Biochemical equilibria are usually modeled iteratively: given one or a few fitted models, if there is a lack of fit or over fitting, a new model with additional or fewer parameters is then fitted, and the process is repeated. The problem with this approach is that different analysts can...

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Autor principal: Radivoyevitch, Tomas
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268910/
https://www.ncbi.nlm.nih.gov/pubmed/18248678
http://dx.doi.org/10.1186/1752-0509-2-15
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author Radivoyevitch, Tomas
author_facet Radivoyevitch, Tomas
author_sort Radivoyevitch, Tomas
collection PubMed
description BACKGROUND: Biochemical equilibria are usually modeled iteratively: given one or a few fitted models, if there is a lack of fit or over fitting, a new model with additional or fewer parameters is then fitted, and the process is repeated. The problem with this approach is that different analysts can propose and select different models and thus extract different binding parameter estimates from the same data. An alternative is to first generate a comprehensive standardized list of plausible models, and to then fit them exhaustively, or semi-exhaustively. RESULTS: A framework is presented in which equilibriums are modeled as pairs (g, h) where g = 0 maps total reactant concentrations (system inputs) into free reactant concentrations (system states) which h then maps into expected values of measurements (system outputs). By letting dissociation constants K(d )be either freely estimated, infinity, zero, or equal to other K(d), and by letting undamaged protein fractions be either freely estimated or 1, many g models are formed. A standard space of g models for ligand-induced protein dimerization equilibria is given. Coupled to an h model, the resulting (g, h) were fitted to dTTP induced R1 dimerization data (R1 is the large subunit of ribonucleotide reductase). Models with the fewest parameters were fitted first. Thereafter, upon fitting a batch, the next batch of models (with one more parameter) was fitted only if the current batch yielded a model that was better (based on the Akaike Information Criterion) than the best model in the previous batch (with one less parameter). Within batches models were fitted in parallel. This semi-exhaustive approach yielded the same best models as an exhaustive model space fit, but in approximately one-fifth the time. CONCLUSION: Comprehensive model space based biochemical equilibrium model selection methods are realizable. Their significance to systems biology as mappings of data into mathematical models warrants their development.
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spelling pubmed-22689102008-03-19 Equilibrium model selection: dTTP induced R1 dimerization Radivoyevitch, Tomas BMC Syst Biol Methodology Article BACKGROUND: Biochemical equilibria are usually modeled iteratively: given one or a few fitted models, if there is a lack of fit or over fitting, a new model with additional or fewer parameters is then fitted, and the process is repeated. The problem with this approach is that different analysts can propose and select different models and thus extract different binding parameter estimates from the same data. An alternative is to first generate a comprehensive standardized list of plausible models, and to then fit them exhaustively, or semi-exhaustively. RESULTS: A framework is presented in which equilibriums are modeled as pairs (g, h) where g = 0 maps total reactant concentrations (system inputs) into free reactant concentrations (system states) which h then maps into expected values of measurements (system outputs). By letting dissociation constants K(d )be either freely estimated, infinity, zero, or equal to other K(d), and by letting undamaged protein fractions be either freely estimated or 1, many g models are formed. A standard space of g models for ligand-induced protein dimerization equilibria is given. Coupled to an h model, the resulting (g, h) were fitted to dTTP induced R1 dimerization data (R1 is the large subunit of ribonucleotide reductase). Models with the fewest parameters were fitted first. Thereafter, upon fitting a batch, the next batch of models (with one more parameter) was fitted only if the current batch yielded a model that was better (based on the Akaike Information Criterion) than the best model in the previous batch (with one less parameter). Within batches models were fitted in parallel. This semi-exhaustive approach yielded the same best models as an exhaustive model space fit, but in approximately one-fifth the time. CONCLUSION: Comprehensive model space based biochemical equilibrium model selection methods are realizable. Their significance to systems biology as mappings of data into mathematical models warrants their development. BioMed Central 2008-02-04 /pmc/articles/PMC2268910/ /pubmed/18248678 http://dx.doi.org/10.1186/1752-0509-2-15 Text en Copyright © 2008 Radivoyevitch; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Methodology Article
Radivoyevitch, Tomas
Equilibrium model selection: dTTP induced R1 dimerization
title Equilibrium model selection: dTTP induced R1 dimerization
title_full Equilibrium model selection: dTTP induced R1 dimerization
title_fullStr Equilibrium model selection: dTTP induced R1 dimerization
title_full_unstemmed Equilibrium model selection: dTTP induced R1 dimerization
title_short Equilibrium model selection: dTTP induced R1 dimerization
title_sort equilibrium model selection: dttp induced r1 dimerization
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268910/
https://www.ncbi.nlm.nih.gov/pubmed/18248678
http://dx.doi.org/10.1186/1752-0509-2-15
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