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

Abstract

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.

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

Publication Date:: Mon May 23 00:00:00 EDT 2016

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

Sponsoring Org.:: USDOE

OSTI Identifier:: 1618921

Alternate Identifier(s):: OSTI ID: 1310268

Grant/Contract Number:: SC0012627

Resource Type:: Published Article

Journal Name:: Genome Biology (Online)

Additional Journal Information:: Journal Name: Genome Biology (Online) Journal Volume: 17 Journal Issue: 1; Journal ID: ISSN 1474-760X

Publisher:: Springer Science + Business Media

Country of Publication:: United Kingdom

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; metabolic networks; flux balance analysis; inverse optimization; objective functions; genome-scale stoichiometric models

Citation Formats


                    Zhao, Qi, Stettner, Arion I., Reznik, Ed, Paschalidis, Ioannis Ch., and Segrè, Daniel. Mapping the landscape of metabolic goals of a cell.  United Kingdom: N. p., 2016. 
Web.  doi:10.1186/s13059-016-0968-2.

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                    Zhao, Qi, Stettner, Arion I., Reznik, Ed, Paschalidis, Ioannis Ch., & Segrè, Daniel. Mapping the landscape of metabolic goals of a cell.  United Kingdom.  https://doi.org/10.1186/s13059-016-0968-2

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                    Zhao, Qi, Stettner, Arion I., Reznik, Ed, Paschalidis, Ioannis Ch., and Segrè, Daniel. Mon .  
"Mapping the landscape of metabolic goals of a cell".  United Kingdom.  https://doi.org/10.1186/s13059-016-0968-2.

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@article{osti_1618921,

  title        = {Mapping the landscape of metabolic goals of a cell},

  author       = {Zhao, Qi and Stettner, Arion I. and Reznik, Ed and Paschalidis, Ioannis Ch. and Segrè, Daniel},

  abstractNote = {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.},

  doi          = {10.1186/s13059-016-0968-2},

  journal      = {Genome Biology (Online)},

  number       = 1,

  volume       = 17,

  place        = {United Kingdom},

  year         = {Mon May 23 00:00:00 EDT 2016},

  month        = {Mon May 23 00:00:00 EDT 2016}

}

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Cited by: 23 works

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Figures / Tables:

Fig. 1: Schematic representation of how FBA and invFBA work. This diagram illustrates concisely the flow of information for invFBA calculations in this work. The right part of the figure displays schematic representations of the set of metabolic fluxes. Each flux vector can also be visualized on a metabolic chartmore »

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Title: Mapping the landscape of metabolic goals of a cell

Abstract

Citation Formats

Figures / Tables:

Long-Term Dynamics of Adaptation in Asexual Populations journal, November 2013

A comprehensive genome‐scale reconstruction of Escherichia coli metabolism—2011 journal, January 2011

Bayesian-based selection of metabolic objective functions journal, December 2006

Cell type– and brain region–resolved mouse brain proteome journal, November 2015

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Data-driven estimation in equilibrium using inverse optimization journal, September 2014

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Systematic Evaluation of Methods for Integration of Transcriptomic Data into Constraint-Based Models of Metabolism journal, April 2014

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Soft constraints-based multiobjective framework for flux balance analysis journal, September 2010

Effect of Escherichia coli biomass composition on central metabolic fluxes predicted by a stoichiometric model journal, October 1998

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Second-Order Selection for Evolvability in a Large Escherichia coli Population journal, March 2011

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Optimization-based framework for inferring and testing hypothesized metabolic objective functions journal, June 2003

Overflow Metabolism in Escherichia coli during Steady-State Growth: Transcriptional Regulation and Effect of the Redox Ratio journal, May 2006

Temporal Expression-based Analysis of Metabolism journal, November 2012

MapMaker and PathTracer for tracking carbon in genome-scale metabolic models journal, March 2016

Adaptation, Clonal Interference, and Frequency-Dependent Interactions in a Long-Term Evolution Experiment with Escherichia coli journal, April 2015

Learning cellular objectives from fluxes by inverse optimization conference, December 2015

The Ability of Flux Balance Analysis to Predict Evolution of Central Metabolism Scales with the Initial Distance to the Optimum journal, June 2013

Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells journal, July 2010

Multidimensional Optimality of Microbial Metabolism journal, May 2012

What is flux balance analysis? journal, March 2010

Flux Coupling Analysis of Genome-Scale Metabolic Network Reconstructions journal, February 2004

Epistasis and Allele Specificity in the Emergence of a Stable Polymorphism in Escherichia coli journal, March 2014

The biomass objective function journal, June 2010

Long-Term Dynamics of Adaptation in Asexual Populations
journal, November 2013

A comprehensive genome‐scale reconstruction of Escherichia coli metabolism—2011
journal, January 2011

Bayesian-based selection of metabolic objective functions
journal, December 2006

Cell type– and brain region–resolved mouse brain proteome
journal, November 2015

Evolutionary Trade-Offs, Pareto Optimality, and the Geometry of Phenotype Space
journal, April 2012

Predicting biological system objectives de novo from internal state measurements
journal, January 2008

Integration of expression data in genome-scale metabolic network reconstructions
journal, January 2012

Data-driven estimation in equilibrium using inverse optimization
journal, September 2014

Intracellular crowding defines the mode and sequence of substrate uptake by Escherichia coli and constrains its metabolic activity
journal, July 2007

Analysis of optimality in natural and perturbed metabolic networks
journal, November 2002

Systematic Evaluation of Methods for Integration of Transcriptomic Data into Constraint-Based Models of Metabolism
journal, April 2014

Detection of transcriptional triggers in the dynamics of microbial growth: application to the respiratorily versatile bacterium Shewanella oneidensis
journal, May 2012

Soft constraints-based multiobjective framework for flux balance analysis
journal, September 2010

Effect of Escherichia coli biomass composition on central metabolic fluxes predicted by a stoichiometric model
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Metabolic flux profiling of Escherichia coli mutants in central carbon metabolism using GC-MS: Metabolic flux profiling in E.��coli
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Second-Order Selection for Evolvability in a Large Escherichia coli Population
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The principle of flux minimization and its application to estimate stationary fluxes in metabolic networks: Flux minimization
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Optimization-based framework for inferring and testing hypothesized metabolic objective functions
journal, June 2003

Overflow Metabolism in Escherichia coli during Steady-State Growth: Transcriptional Regulation and Effect of the Redox Ratio
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Temporal Expression-based Analysis of Metabolism
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MapMaker and PathTracer for tracking carbon in genome-scale metabolic models
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Adaptation, Clonal Interference, and Frequency-Dependent Interactions in a Long-Term Evolution Experiment with Escherichia coli
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Learning cellular objectives from fluxes by inverse optimization
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The Ability of Flux Balance Analysis to Predict Evolution of Central Metabolism Scales with the Initial Distance to the Optimum
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Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells
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Multidimensional Optimality of Microbial Metabolism
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Flux Coupling Analysis of Genome-Scale Metabolic Network Reconstructions
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The biomass objective function
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