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Optimization based automated curation of metabolic reconstructions

BACKGROUND: Currently, there exists tens of different microbial and eukaryotic metabolic reconstructions (e.g., Escherichia coli, Saccharomyces cerevisiae, Bacillus subtilis) with many more under development. All of these reconstructions are inherently incomplete with some functionalities missing du...

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Autores principales: Satish Kumar, Vinay, Dasika, Madhukar S, Maranas, Costas D
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933441/
https://www.ncbi.nlm.nih.gov/pubmed/17584497
http://dx.doi.org/10.1186/1471-2105-8-212
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author Satish Kumar, Vinay
Dasika, Madhukar S
Maranas, Costas D
author_facet Satish Kumar, Vinay
Dasika, Madhukar S
Maranas, Costas D
author_sort Satish Kumar, Vinay
collection PubMed
description BACKGROUND: Currently, there exists tens of different microbial and eukaryotic metabolic reconstructions (e.g., Escherichia coli, Saccharomyces cerevisiae, Bacillus subtilis) with many more under development. All of these reconstructions are inherently incomplete with some functionalities missing due to the lack of experimental and/or homology information. A key challenge in the automated generation of genome-scale reconstructions is the elucidation of these gaps and the subsequent generation of hypotheses to bridge them. RESULTS: In this work, an optimization based procedure is proposed to identify and eliminate network gaps in these reconstructions. First we identify the metabolites in the metabolic network reconstruction which cannot be produced under any uptake conditions and subsequently we identify the reactions from a customized multi-organism database that restores the connectivity of these metabolites to the parent network using four mechanisms. This connectivity restoration is hypothesized to take place through four mechanisms: a) reversing the directionality of one or more reactions in the existing model, b) adding reaction from another organism to provide functionality absent in the existing model, c) adding external transport mechanisms to allow for importation of metabolites in the existing model and d) restore flow by adding intracellular transport reactions in multi-compartment models. We demonstrate this procedure for the genome- scale reconstruction of Escherichia coli and also Saccharomyces cerevisiae wherein compartmentalization of intra-cellular reactions results in a more complex topology of the metabolic network. We determine that about 10% of metabolites in E. coli and 30% of metabolites in S. cerevisiae cannot carry any flux. Interestingly, the dominant flow restoration mechanism is directionality reversals of existing reactions in the respective models. CONCLUSION: We have proposed systematic methods to identify and fill gaps in genome-scale metabolic reconstructions. The identified gaps can be filled both by making modifications in the existing model and by adding missing reactions by reconciling multi-organism databases of reactions with existing genome-scale models. Computational results provide a list of hypotheses to be queried further and tested experimentally.
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spelling pubmed-19334412007-07-26 Optimization based automated curation of metabolic reconstructions Satish Kumar, Vinay Dasika, Madhukar S Maranas, Costas D BMC Bioinformatics Methodology Article BACKGROUND: Currently, there exists tens of different microbial and eukaryotic metabolic reconstructions (e.g., Escherichia coli, Saccharomyces cerevisiae, Bacillus subtilis) with many more under development. All of these reconstructions are inherently incomplete with some functionalities missing due to the lack of experimental and/or homology information. A key challenge in the automated generation of genome-scale reconstructions is the elucidation of these gaps and the subsequent generation of hypotheses to bridge them. RESULTS: In this work, an optimization based procedure is proposed to identify and eliminate network gaps in these reconstructions. First we identify the metabolites in the metabolic network reconstruction which cannot be produced under any uptake conditions and subsequently we identify the reactions from a customized multi-organism database that restores the connectivity of these metabolites to the parent network using four mechanisms. This connectivity restoration is hypothesized to take place through four mechanisms: a) reversing the directionality of one or more reactions in the existing model, b) adding reaction from another organism to provide functionality absent in the existing model, c) adding external transport mechanisms to allow for importation of metabolites in the existing model and d) restore flow by adding intracellular transport reactions in multi-compartment models. We demonstrate this procedure for the genome- scale reconstruction of Escherichia coli and also Saccharomyces cerevisiae wherein compartmentalization of intra-cellular reactions results in a more complex topology of the metabolic network. We determine that about 10% of metabolites in E. coli and 30% of metabolites in S. cerevisiae cannot carry any flux. Interestingly, the dominant flow restoration mechanism is directionality reversals of existing reactions in the respective models. CONCLUSION: We have proposed systematic methods to identify and fill gaps in genome-scale metabolic reconstructions. The identified gaps can be filled both by making modifications in the existing model and by adding missing reactions by reconciling multi-organism databases of reactions with existing genome-scale models. Computational results provide a list of hypotheses to be queried further and tested experimentally. BioMed Central 2007-06-20 /pmc/articles/PMC1933441/ /pubmed/17584497 http://dx.doi.org/10.1186/1471-2105-8-212 Text en Copyright © 2007 Satish Kumar et al; 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
Satish Kumar, Vinay
Dasika, Madhukar S
Maranas, Costas D
Optimization based automated curation of metabolic reconstructions
title Optimization based automated curation of metabolic reconstructions
title_full Optimization based automated curation of metabolic reconstructions
title_fullStr Optimization based automated curation of metabolic reconstructions
title_full_unstemmed Optimization based automated curation of metabolic reconstructions
title_short Optimization based automated curation of metabolic reconstructions
title_sort optimization based automated curation of metabolic reconstructions
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933441/
https://www.ncbi.nlm.nih.gov/pubmed/17584497
http://dx.doi.org/10.1186/1471-2105-8-212
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