Dataset Information

Optimization based automated curation of metabolic reconstructions.

ABSTRACT:

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.

SUBMITTER: Satish Kumar V

PROVIDER: S-EPMC1933441 | biostudies-literature | 2007 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Optimization based automated curation of metabolic reconstructions.

Satish Kumar Vinay V Dasika Madhukar S MS Maranas Costas D CD

BMC bioinformatics 20070620

<h4>Background</h4>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 genera ...[more]

PMID: 17584497

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Dataset Information

Optimization based automated curation of metabolic reconstructions.

Background

Results

Conclusion

Publications

Optimization based automated curation of metabolic reconstructions.

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