2.50
Hdl Handle:
http://hdl.handle.net/10033/142740
Title:
Reconciliation of genome-scale metabolic reconstructions for comparative systems analysis.
Authors:
Oberhardt, Matthew A; Puchałka, Jacek; Martins dos Santos, Vítor A P; Papin, Jason A
Abstract:
In the past decade, over 50 genome-scale metabolic reconstructions have been built for a variety of single- and multi- cellular organisms. These reconstructions have enabled a host of computational methods to be leveraged for systems-analysis of metabolism, leading to greater understanding of observed phenotypes. These methods have been sparsely applied to comparisons between multiple organisms, however, due mainly to the existence of differences between reconstructions that are inherited from the respective reconstruction processes of the organisms to be compared. To circumvent this obstacle, we developed a novel process, termed metabolic network reconciliation, whereby non-biological differences are removed from genome-scale reconstructions while keeping the reconstructions as true as possible to the underlying biological data on which they are based. This process was applied to two organisms of great importance to disease and biotechnological applications, Pseudomonas aeruginosa and Pseudomonas putida, respectively. The result is a pair of revised genome-scale reconstructions for these organisms that can be analyzed at a systems level with confidence that differences are indicative of true biological differences (to the degree that is currently known), rather than artifacts of the reconstruction process. The reconstructions were re-validated with various experimental data after reconciliation. With the reconciled and validated reconstructions, we performed a genome-wide comparison of metabolic flexibility between P. aeruginosa and P. putida that generated significant new insight into the underlying biology of these important organisms. Through this work, we provide a novel methodology for reconciling models, present new genome-scale reconstructions of P. aeruginosa and P. putida that can be directly compared at a network level, and perform a network-wide comparison of the two species. These reconstructions provide fresh insights into the metabolic similarities and differences between these important Pseudomonads, and pave the way towards full comparative analysis of genome-scale metabolic reconstructions of multiple species.
Affiliation:
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
Citation:
Reconciliation of genome-scale metabolic reconstructions for comparative systems analysis. 2011, 7 (3):e1001116 PLoS Comput. Biol.
Journal:
PLoS computational biology
Issue Date:
Mar-2011
URI:
http://hdl.handle.net/10033/142740
DOI:
10.1371/journal.pcbi.1001116
PubMed ID:
21483480
Type:
Article
Language:
en
ISSN:
1553-7358
Appears in Collections:
Publications of Dept. Gene Regulation and Differentiation (RDIF)

Full metadata record

DC FieldValue Language
dc.contributor.authorOberhardt, Matthew Aen
dc.contributor.authorPuchałka, Jaceken
dc.contributor.authorMartins dos Santos, Vítor A Pen
dc.contributor.authorPapin, Jason Aen
dc.date.accessioned2011-09-20T11:51:50Z-
dc.date.available2011-09-20T11:51:50Z-
dc.date.issued2011-03-
dc.identifier.citationReconciliation of genome-scale metabolic reconstructions for comparative systems analysis. 2011, 7 (3):e1001116 PLoS Comput. Biol.en
dc.identifier.issn1553-7358-
dc.identifier.pmid21483480-
dc.identifier.doi10.1371/journal.pcbi.1001116-
dc.identifier.urihttp://hdl.handle.net/10033/142740-
dc.description.abstractIn the past decade, over 50 genome-scale metabolic reconstructions have been built for a variety of single- and multi- cellular organisms. These reconstructions have enabled a host of computational methods to be leveraged for systems-analysis of metabolism, leading to greater understanding of observed phenotypes. These methods have been sparsely applied to comparisons between multiple organisms, however, due mainly to the existence of differences between reconstructions that are inherited from the respective reconstruction processes of the organisms to be compared. To circumvent this obstacle, we developed a novel process, termed metabolic network reconciliation, whereby non-biological differences are removed from genome-scale reconstructions while keeping the reconstructions as true as possible to the underlying biological data on which they are based. This process was applied to two organisms of great importance to disease and biotechnological applications, Pseudomonas aeruginosa and Pseudomonas putida, respectively. The result is a pair of revised genome-scale reconstructions for these organisms that can be analyzed at a systems level with confidence that differences are indicative of true biological differences (to the degree that is currently known), rather than artifacts of the reconstruction process. The reconstructions were re-validated with various experimental data after reconciliation. With the reconciled and validated reconstructions, we performed a genome-wide comparison of metabolic flexibility between P. aeruginosa and P. putida that generated significant new insight into the underlying biology of these important organisms. Through this work, we provide a novel methodology for reconciling models, present new genome-scale reconstructions of P. aeruginosa and P. putida that can be directly compared at a network level, and perform a network-wide comparison of the two species. These reconstructions provide fresh insights into the metabolic similarities and differences between these important Pseudomonads, and pave the way towards full comparative analysis of genome-scale metabolic reconstructions of multiple species.en
dc.language.isoenen
dc.subject.meshAlgorithmsen
dc.subject.meshBiotechnologyen
dc.subject.meshComputational Biologyen
dc.subject.meshComputer Simulationen
dc.subject.meshDatabases, Factualen
dc.subject.meshGene Expression Regulation, Bacterialen
dc.subject.meshGenomeen
dc.subject.meshGenome, Bacterialen
dc.subject.meshMetabolic Networks and Pathwaysen
dc.subject.meshPhenotypeen
dc.subject.meshPseudomonasen
dc.subject.meshReproducibility of Resultsen
dc.subject.meshSoftwareen
dc.subject.meshSpecies Specificityen
dc.titleReconciliation of genome-scale metabolic reconstructions for comparative systems analysis.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.en
dc.identifier.journalPLoS computational biologyen

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