Efficient Reconstruction of Predictive Consensus Metabolic Network Models

Understanding cellular function requires accurate, comprehensive representations of metabolism. Genome-scale, constraint-based metabolic models (GSMs) provide such representations, but their usability is often hampered by inconsistencies at various levels, in particular for concurrent models. COMMGEN, our tool for COnsensus Metabolic Model GENeration, automatically identifies inconsistencies between concurrent models and semi-automatically resolves them, thereby contributing to consolidate knowledge of metabolic function. Tests of COMMGEN for four organisms showed that automatically generated consensus models were predictive and that they substantially increased coherence of knowledge representation. COMMGEN ought to be particularly useful for complex scenarios in which manual curation does not scale, such as for eukaryotic organisms, microbial communities, and host-pathogen interactions.

[1]  Desmond S. Lun,et al.  Interpreting Expression Data with Metabolic Flux Models: Predicting Mycobacterium tuberculosis Mycolic Acid Production , 2009, PLoS Comput. Biol..

[2]  B. Palsson,et al.  Towards multidimensional genome annotation , 2006, Nature Reviews Genetics.

[3]  Kellen L. Olszewski,et al.  Reconstruction and flux-balance analysis of the Plasmodium falciparum metabolic network , 2010, Molecular systems biology.

[4]  B. Palsson,et al.  Genome-scale Reconstruction of Metabolic Network in Bacillus subtilis Based on High-throughput Phenotyping and Gene Essentiality Data* , 2007, Journal of Biological Chemistry.

[5]  Markus J. Herrgård,et al.  Reconstruction and validation of Saccharomyces cerevisiae iND750, a fully compartmentalized genome-scale metabolic model. , 2004, Genome research.

[6]  Jason A. Papin,et al.  Comparative Metabolic Systems Analysis of Pathogenic Burkholderia , 2013, Journal of bacteriology.

[7]  Rick L. Stevens,et al.  High-throughput generation, optimization and analysis of genome-scale metabolic models , 2010, Nature Biotechnology.

[8]  Gerbert A. Jansen,et al.  Critical assessment of human metabolic pathway databases: a stepping stone for future integration , 2011, BMC Systems Biology.

[9]  A. Burgard,et al.  Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol. , 2011, Nature chemical biology.

[10]  Costas D. Maranas,et al.  MetRxn: a knowledgebase of metabolites and reactions spanning metabolic models and databases , 2012, BMC Bioinformatics.

[11]  U. Sauer,et al.  Metabolic functions of duplicate genes in Saccharomyces cerevisiae. , 2005, Genome research.

[12]  Vinay Satish Kumar,et al.  GrowMatch: An Automated Method for Reconciling In Silico/In Vivo Growth Predictions , 2009, PLoS Comput. Biol..

[13]  Ronan M. T. Fleming,et al.  Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0 , 2007, Nature Protocols.

[14]  Ronan M. T. Fleming,et al.  fastGapFill: efficient gap filling in metabolic networks , 2014, Bioinform..

[15]  Joshua A. Lerman,et al.  Genome-scale metabolic reconstructions of multiple Escherichia coli strains highlight strain-specific adaptations to nutritional environments , 2013, Proceedings of the National Academy of Sciences.

[16]  Jörg Stelling,et al.  Predicting network functions with nested patterns , 2014, Nature Communications.

[17]  Kathleen Marchal,et al.  A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella Typhimurium LT2 , 2011, BMC Systems Biology.

[18]  Rick L Stevens,et al.  iBsu1103: a new genome-scale metabolic model of Bacillus subtilis based on SEED annotations , 2009, Genome Biology.

[19]  Jonathan M. Dreyfuss,et al.  Reconstruction and Validation of a Genome-Scale Metabolic Model for the Filamentous Fungus Neurospora crassa Using FARM , 2013, PLoS Comput. Biol..

[20]  S. Henry,et al.  Revising the Representation of Fatty Acid, Glycerolipid, and Glycerophospholipid Metabolism in the Consensus Model of Yeast Metabolism. , 2013, Industrial biotechnology.

[21]  Jason A. Papin,et al.  Genome-Scale Reconstruction and Analysis of the Pseudomonas putida KT2440 Metabolic Network Facilitates Applications in Biotechnology , 2008, PLoS Comput. Biol..

[22]  E. Rubin,et al.  Genes required for mycobacterial growth defined by high density mutagenesis , 2003, Molecular microbiology.

[23]  Bernhard O. Palsson,et al.  Connecting Extracellular Metabolomic Measurements to Intracellular Flux States in Yeast , 2022 .

[24]  N. Price,et al.  Probabilistic integrative modeling of genome-scale metabolic and regulatory networks in Escherichia coli and Mycobacterium tuberculosis , 2010, Proceedings of the National Academy of Sciences.

[25]  Sandra Fillebrown,et al.  The MathWorks' MATLAB , 1996 .

[26]  Bonnie Berger,et al.  MetaMerge: scaling up genome-scale metabolic reconstructions with application to Mycobacterium tuberculosis , 2012, Genome Biology.

[27]  J. Ramos,et al.  Identification of conditionally essential genes for growth of Pseudomonas putida KT2440 on minimal medium through the screening of a genome-wide mutant library. , 2010, Environmental microbiology.

[28]  Markus J. Herrgård,et al.  A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology , 2008, Nature Biotechnology.

[29]  Bernhard O. Palsson,et al.  Optimizing genome-scale network reconstructions , 2014, Nature Biotechnology.

[30]  Neil Swainston,et al.  Integration of metabolic databases for the reconstruction of genome-scale metabolic networks , 2010, BMC Systems Biology.

[31]  Thomas Bernard,et al.  MetaNetX.org: a website and repository for accessing, analysing and manipulating metabolic networks , 2013, Bioinform..

[32]  Hiroaki Kitano,et al.  The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models , 2003, Bioinform..

[33]  Thomas Bernard,et al.  Reconciliation of metabolites and biochemical reactions for metabolic networks , 2012, Briefings Bioinform..

[34]  Adam M. Feist,et al.  A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information , 2007, Molecular systems biology.

[35]  Antoine H. C. van Kampen,et al.  Consensus and conflict cards for metabolic pathway databases , 2013, BMC Systems Biology.

[36]  B. Palsson,et al.  A protocol for generating a high-quality genome-scale metabolic reconstruction , 2010 .

[37]  Eytan Ruppin,et al.  Network-based prediction of metabolic enzymes' subcellular localization , 2009, Bioinform..

[38]  Sayed-Amir Marashi,et al.  Modeling the Differences in Biochemical Capabilities of Pseudomonas Species by Flux Balance Analysis: How Good Are Genome-Scale Metabolic Networks at Predicting the Differences? , 2014, TheScientificWorldJournal.

[39]  S. Klamt,et al.  GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosis metabolism , 2007, Genome Biology.

[40]  Intawat Nookaew,et al.  The genome-scale metabolic model iIN800 of Saccharomyces cerevisiae and its validation: a scaffold to query lipid metabolism , 2008, BMC Syst. Biol..

[41]  Yaniv Lubling,et al.  An integrated open framework for thermodynamics of reactions that combines accuracy and coverage , 2012, Bioinform..

[42]  V. M. D. Martins dos Santos,et al.  Systems-level modeling of mycobacterial metabolism for the identification of new (multi-)drug targets. , 2014, Seminars in immunology.

[43]  Ronan M. T. Fleming,et al.  A community-driven global reconstruction of human metabolism , 2013, Nature Biotechnology.

[44]  Zachary A. King,et al.  Constraint-based models predict metabolic and associated cellular functions , 2014, Nature Reviews Genetics.

[45]  Martijn J. Schuemie,et al.  A dictionary to identify small molecules and drugs in free text , 2009, Bioinform..

[46]  Bernhard O. Palsson,et al.  Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets , 2007 .

[47]  Jason A. Papin,et al.  Reconciliation of Genome-Scale Metabolic Reconstructions for Comparative Systems Analysis , 2011, PLoS Comput. Biol..

[48]  B. Matthews Comparison of the predicted and observed secondary structure of T4 phage lysozyme. , 1975, Biochimica et biophysica acta.

[49]  Bernhard O. Palsson,et al.  A genome-scale metabolic reconstruction of Pseudomonas putida KT2440: iJN746 as a cell factory , 2008, BMC Systems Biology.

[50]  Eytan Ruppin,et al.  iMAT: an integrative metabolic analysis tool , 2010, Bioinform..