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Bordbar2010_Macrophage_Metabolism


ABSTRACT: This is the genome scale metabolic reconstruction of the human alveloar macrophage, iAB-AMØ-1410, described in the article: Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions. Bordbar A, Lewis NE, Schellenberger J, Palsson BØ, Jamshidi N. Mol Syst Biol. 2010 Oct 19;6:422. PMID: 20959820 , DOI: 10.1038/msb.2010.68 Abstract: Metabolic coupling of Mycobacterium tuberculosis to its host is foundational to its pathogenesis. Computational genome-scale metabolic models have shown utility in integrating -omic as well as physiologic data for systemic, mechanistic analysis of metabolism. To date, integrative analysis of host-pathogen interactions using in silico mass-balanced, genome-scale models has not been performed. We, therefore, constructed a cell-specific alveolar macrophage model, iAB-AMØ-1410, from the global human metabolic reconstruction, Recon 1. The model successfully predicted experimentally verified ATP and nitric oxide production rates in macrophages. This model was then integrated with an M. tuberculosis H37Rv model, iNJ661, to build an integrated host-pathogen genome-scale reconstruction, iAB-AMØ-1410-Mt-661. The integrated host-pathogen network enables simulation of the metabolic changes during infection. The resulting reaction activity and gene essentiality targets of the integrated model represent an altered infectious state. High-throughput data from infected macrophages were mapped onto the host-pathogen network and were able to describe three distinct pathological states. Integrated host-pathogen reconstructions thus form a foundation upon which understanding the biology and pathophysiology of infections can be developed. This model was downloaded from the supplementary materials ( link ) to the article. To make this file valid SBML the units of all parameters where changed from mmole per gDW per hour to mmole per hour and the empty reactions with the ids R_EX_retpalm_LPAREN_e_RPAREN_ were removed. The model can be used eg. fpr FBA with the COBRA toolbox , amongst others. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

SUBMITTER: Lukas Endler  

PROVIDER: MODEL1011090001 | BioModels | 2005-01-01

REPOSITORIES: BioModels

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Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions.

Bordbar Aarash A   Lewis Nathan E NE   Schellenberger Jan J   Palsson Bernhard Ø BØ   Jamshidi Neema N  

Molecular systems biology 20101001


Metabolic coupling of Mycobacterium tuberculosis to its host is foundational to its pathogenesis. Computational genome-scale metabolic models have shown utility in integrating -omic as well as physiologic data for systemic, mechanistic analysis of metabolism. To date, integrative analysis of host-pathogen interactions using in silico mass-balanced, genome-scale models has not been performed. We, therefore, constructed a cell-specific alveolar macrophage model, iAB-AMØ-1410, from the global human  ...[more]

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