Mapping the landscape of metabolic goals of a cell

Zhao, Qi; Stettner, Arion I.; Reznik, Ed; Paschalidis, Ioannis Ch.; Segrè, Daniel

doi:10.1186/s13059-016-0968-2

Title: Mapping the landscape of metabolic goals of a cell

Journal Article · Mon May 23 00:00:00 EDT 2016 · Genome Biology (Online)

DOI:https://doi.org/10.1186/s13059-016-0968-2· OSTI ID:1618921

Zhao, Qi; Stettner, Arion I.; Reznik, Ed; Paschalidis, Ioannis Ch.; Segrè, Daniel

Here, genome-scale flux balance models of metabolism provide testable predictions of all metabolic rates in an organism, by assuming that the cell is optimizing a metabolic goal known as the objective function. We introduce an efficient inverse flux balance analysis (invFBA) approach, based on linear programming duality, to characterize the space of possible objective functions compatible with measured fluxes. After testing our algorithm on simulated E. coli data and time-dependent S. oneidensis fluxes inferred from gene expression, we apply our inverse approach to flux measurements in long-term evolved E. coli strains, revealing objective functions that provide insight into metabolic adaptation trajectories.

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Research Organization:: Boston Univ., MA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0012627

OSTI ID:: 1618921

Alternate ID(s):: OSTI ID: 1310268

Journal Information:: Genome Biology (Online), Journal Name: Genome Biology (Online) Vol. 17 Journal Issue: 1; ISSN 1474-760X

Publisher:: Springer Science + Business MediaCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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Cited by: 23 works

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References (30)

Long-Term Dynamics of Adaptation in Asexual Populations Wiser, M. J.; Ribeck, N.; Lenski, R. E. Science, Vol. 342, Issue 6164 https://doi.org/10.1126/science.1243357	journal	November 2013
A comprehensive genome‐scale reconstruction of Escherichia coli metabolism—2011 Orth, Jeffrey D.; Conrad, Tom M.; Na, Jessica Molecular Systems Biology, Vol. 7, Issue 1 https://doi.org/10.1038/msb.2011.65	journal	January 2011
Bayesian-based selection of metabolic objective functions Knorr, A. L.; Jain, R.; Srivastava, R. Bioinformatics, Vol. 23, Issue 3 https://doi.org/10.1093/bioinformatics/btl619	journal	December 2006
Cell type– and brain region–resolved mouse brain proteome Sharma, Kirti; Schmitt, Sebastian; Bergner, Caroline G. Nature Neuroscience, Vol. 18, Issue 12 https://doi.org/10.1038/nn.4160	journal	November 2015
Evolutionary Trade-Offs, Pareto Optimality, and the Geometry of Phenotype Space Shoval, O.; Sheftel, H.; Shinar, G. Science, Vol. 336, Issue 6085 https://doi.org/10.1126/science.1217405	journal	April 2012
Predicting biological system objectives de novo from internal state measurements Gianchandani, Erwin P.; Oberhardt, Matthew A.; Burgard, Anthony P. BMC Bioinformatics, Vol. 9, Issue 1 https://doi.org/10.1186/1471-2105-9-43	journal	January 2008
Integration of expression data in genome-scale metabolic network reconstructions Blazier, Anna S.; Papin, Jason A. Frontiers in Physiology, Vol. 3 https://doi.org/10.3389/fphys.2012.00299	journal	January 2012
Data-driven estimation in equilibrium using inverse optimization Bertsimas, Dimitris; Gupta, Vishal; Paschalidis, Ioannis Ch. Mathematical Programming, Vol. 153, Issue 2 https://doi.org/10.1007/s10107-014-0819-4	journal	September 2014
Intracellular crowding defines the mode and sequence of substrate uptake by Escherichia coli and constrains its metabolic activity Beg, Q. K.; Vazquez, A.; Ernst, J. Proceedings of the National Academy of Sciences, Vol. 104, Issue 31 https://doi.org/10.1073/pnas.0609845104	journal	July 2007
Analysis of optimality in natural and perturbed metabolic networks Segre, D.; Vitkup, D.; Church, G. M. Proceedings of the National Academy of Sciences, Vol. 99, Issue 23 https://doi.org/10.1073/pnas.232349399	journal	November 2002
Systematic Evaluation of Methods for Integration of Transcriptomic Data into Constraint-Based Models of Metabolism Machado, Daniel; Herrgård, Markus PLoS Computational Biology, Vol. 10, Issue 4 https://doi.org/10.1371/journal.pcbi.1003580	journal	April 2014
Detection of transcriptional triggers in the dynamics of microbial growth: application to the respiratorily versatile bacterium Shewanella oneidensis Beg, Qasim K.; Zampieri, Mattia; Klitgord, Niels Nucleic Acids Research, Vol. 40, Issue 15 https://doi.org/10.1093/nar/gks467	journal	May 2012
Soft constraints-based multiobjective framework for flux balance analysis Nagrath, Deepak; Avila-Elchiver, Marco; Berthiaume, François Metabolic Engineering, Vol. 12, Issue 5 https://doi.org/10.1016/j.ymben.2010.05.003	journal	September 2010
Effect of Escherichia coli biomass composition on central metabolic fluxes predicted by a stoichiometric model Pramanik, J.; Keasling, J. D. Biotechnology and Bioengineering, Vol. 60, Issue 2, p. 230-238 https://doi.org/10.1002/(SICI)1097-0290(19981020)60:2<230::AID-BIT10>3.0.CO;2-Q	journal	October 1998
Metabolic flux profiling of Escherichia coli mutants in central carbon metabolism using GC-MS: Metabolic flux profiling in E.��coli Fischer, Eliane; Sauer, Uwe European Journal of Biochemistry, Vol. 270, Issue 5 https://doi.org/10.1046/j.1432-1033.2003.03448.x	journal	March 2003
Second-Order Selection for Evolvability in a Large Escherichia coli Population Woods, R. J.; Barrick, J. E.; Cooper, T. F. Science, Vol. 331, Issue 6023 https://doi.org/10.1126/science.1198914	journal	March 2011
The principle of flux minimization and its application to estimate stationary fluxes in metabolic networks: Flux minimization Holzhütter, Hermann-Georg European Journal of Biochemistry, Vol. 271, Issue 14 https://doi.org/10.1111/j.1432-1033.2004.04213.x	journal	June 2004
Optimization-based framework for inferring and testing hypothesized metabolic objective functions Burgard, Anthony P.; Maranas, Costas D. Biotechnology and Bioengineering, Vol. 82, Issue 6 https://doi.org/10.1002/bit.10617	journal	June 2003
Overflow Metabolism in Escherichia coli during Steady-State Growth: Transcriptional Regulation and Effect of the Redox Ratio Vemuri, G. N.; Altman, E.; Sangurdekar, D. P. Applied and Environmental Microbiology, Vol. 72, Issue 5 https://doi.org/10.1128/AEM.72.5.3653-3661.2006	journal	May 2006
Temporal Expression-based Analysis of Metabolism Collins, Sara B.; Reznik, Ed; Segrè, Daniel PLoS Computational Biology, Vol. 8, Issue 11 https://doi.org/10.1371/journal.pcbi.1002781	journal	November 2012
MapMaker and PathTracer for tracking carbon in genome-scale metabolic models Tervo, Christopher J.; Reed, Jennifer L. Biotechnology Journal, Vol. 11, Issue 5 https://doi.org/10.1002/biot.201500267	journal	March 2016
Adaptation, Clonal Interference, and Frequency-Dependent Interactions in a Long-Term Evolution Experiment with Escherichia coli Maddamsetti, Rohan; Lenski, Richard E.; Barrick, Jeffrey E. Genetics, Vol. 200, Issue 2 https://doi.org/10.1534/genetics.115.176677	journal	April 2015
Learning cellular objectives from fluxes by inverse optimization Zhao, Qi; Stettner, Arion; Reznik, Ed 2015 54th IEEE Conference on Decision and Control (CDC) https://doi.org/10.1109/CDC.2015.7402386	conference	December 2015
The Ability of Flux Balance Analysis to Predict Evolution of Central Metabolism Scales with the Initial Distance to the Optimum Harcombe, William R.; Delaney, Nigel F.; Leiby, Nicholas PLoS Computational Biology, Vol. 9, Issue 6 https://doi.org/10.1371/journal.pcbi.1003091	journal	June 2013
Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells Taniguchi, Y.; Choi, P. J.; Li, G. -W. Science, Vol. 329, Issue 5991 https://doi.org/10.1126/science.1188308	journal	July 2010
Multidimensional Optimality of Microbial Metabolism Schuetz, R.; Zamboni, N.; Zampieri, M. Science, Vol. 336, Issue 6081 https://doi.org/10.1126/science.1216882	journal	May 2012
What is flux balance analysis? Orth, Jeffrey D.; Thiele, Ines; Palsson, Bernhard Ø Nature Biotechnology, Vol. 28, Issue 3 https://doi.org/10.1038/nbt.1614	journal	March 2010
Flux Coupling Analysis of Genome-Scale Metabolic Network Reconstructions Burgard, A. P. Genome Research, Vol. 14, Issue 2 https://doi.org/10.1101/gr.1926504	journal	February 2004
Epistasis and Allele Specificity in the Emergence of a Stable Polymorphism in Escherichia coli Plucain, J.; Hindre, T.; Le Gac, M. Science, Vol. 343, Issue 6177 https://doi.org/10.1126/science.1248688	journal	March 2014
The biomass objective function Feist, Adam M.; Palsson, Bernhard O. Current Opinion in Microbiology, Vol. 13, Issue 3 https://doi.org/10.1016/j.mib.2010.03.003	journal	June 2010