Cargando…
Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions
BACKGROUND: The iJO1366 reconstruction of the metabolic network of Escherichia coli is one of the most complete and accurate metabolic reconstructions available for any organism. Still, because our knowledge of even well-studied model organisms such as this one is incomplete, this network reconstruc...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423039/ https://www.ncbi.nlm.nih.gov/pubmed/22548736 http://dx.doi.org/10.1186/1752-0509-6-30 |
_version_ | 1782241076761853952 |
---|---|
author | Orth, Jeffrey D Palsson, BernhardØ |
author_facet | Orth, Jeffrey D Palsson, BernhardØ |
author_sort | Orth, Jeffrey D |
collection | PubMed |
description | BACKGROUND: The iJO1366 reconstruction of the metabolic network of Escherichia coli is one of the most complete and accurate metabolic reconstructions available for any organism. Still, because our knowledge of even well-studied model organisms such as this one is incomplete, this network reconstruction contains gaps and possible errors. There are a total of 208 blocked metabolites in iJO1366, representing gaps in the network. RESULTS: A new model improvement workflow was developed to compare model based phenotypic predictions to experimental data to fill gaps and correct errors. A Keio Collection based dataset of E. coli gene essentiality was obtained from literature data and compared to model predictions. The SMILEY algorithm was then used to predict the most likely missing reactions in the reconstructed network, adding reactions from a KEGG based universal set of metabolic reactions. The feasibility of these putative reactions was determined by comparing updated versions of the model to the experimental dataset, and genes were predicted for the most feasible reactions. CONCLUSIONS: Numerous improvements to the iJO1366 metabolic reconstruction were suggested by these analyses. Experiments were performed to verify several computational predictions, including a new mechanism for growth on myo-inositol. The other predictions made in this study should be experimentally verifiable by similar means. Validating all of the predictions made here represents a substantial but important undertaking. |
format | Online Article Text |
id | pubmed-3423039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-34230392012-08-21 Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions Orth, Jeffrey D Palsson, BernhardØ BMC Syst Biol Research Article BACKGROUND: The iJO1366 reconstruction of the metabolic network of Escherichia coli is one of the most complete and accurate metabolic reconstructions available for any organism. Still, because our knowledge of even well-studied model organisms such as this one is incomplete, this network reconstruction contains gaps and possible errors. There are a total of 208 blocked metabolites in iJO1366, representing gaps in the network. RESULTS: A new model improvement workflow was developed to compare model based phenotypic predictions to experimental data to fill gaps and correct errors. A Keio Collection based dataset of E. coli gene essentiality was obtained from literature data and compared to model predictions. The SMILEY algorithm was then used to predict the most likely missing reactions in the reconstructed network, adding reactions from a KEGG based universal set of metabolic reactions. The feasibility of these putative reactions was determined by comparing updated versions of the model to the experimental dataset, and genes were predicted for the most feasible reactions. CONCLUSIONS: Numerous improvements to the iJO1366 metabolic reconstruction were suggested by these analyses. Experiments were performed to verify several computational predictions, including a new mechanism for growth on myo-inositol. The other predictions made in this study should be experimentally verifiable by similar means. Validating all of the predictions made here represents a substantial but important undertaking. BioMed Central 2012-05-01 /pmc/articles/PMC3423039/ /pubmed/22548736 http://dx.doi.org/10.1186/1752-0509-6-30 Text en Copyright ©2012 Orth and Palsson; 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 | Research Article Orth, Jeffrey D Palsson, BernhardØ Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions |
title | Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions |
title_full | Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions |
title_fullStr | Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions |
title_full_unstemmed | Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions |
title_short | Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions |
title_sort | gap-filling analysis of the ijo1366 escherichia coli metabolic network reconstruction for discovery of metabolic functions |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423039/ https://www.ncbi.nlm.nih.gov/pubmed/22548736 http://dx.doi.org/10.1186/1752-0509-6-30 |
work_keys_str_mv | AT orthjeffreyd gapfillinganalysisoftheijo1366escherichiacolimetabolicnetworkreconstructionfordiscoveryofmetabolicfunctions AT palssonbernhardø gapfillinganalysisoftheijo1366escherichiacolimetabolicnetworkreconstructionfordiscoveryofmetabolicfunctions |