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      COBRApy: COnstraints-Based Reconstruction and Analysis for Python

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          Abstract

          Background

          COnstraint-Based Reconstruction and Analysis (COBRA) methods are widely used for genome-scale modeling of metabolic networks in both prokaryotes and eukaryotes. Due to the successes with metabolism, there is an increasing effort to apply COBRA methods to reconstruct and analyze integrated models of cellular processes. The COBRA Toolbox for MATLAB is a leading software package for genome-scale analysis of metabolism; however, it was not designed to elegantly capture the complexity inherent in integrated biological networks and lacks an integration framework for the multiomics data used in systems biology. The openCOBRA Project is a community effort to promote constraints-based research through the distribution of freely available software.

          Results

          Here, we describe COBRA for Python (COBRApy), a Python package that provides support for basic COBRA methods. COBRApy is designed in an object-oriented fashion that facilitates the representation of the complex biological processes of metabolism and gene expression. COBRApy does not require MATLAB to function; however, it includes an interface to the COBRA Toolbox for MATLAB to facilitate use of legacy codes. For improved performance, COBRApy includes parallel processing support for computationally intensive processes.

          Conclusion

          COBRApy is an object-oriented framework designed to meet the computational challenges associated with the next generation of stoichiometric constraint-based models and high-density omics data sets.

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          Most cited references42

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          What is flux balance analysis?

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            Quantitative prediction of cellular metabolism with constraint-based models: the COBRA Toolbox v2.0.

            Over the past decade, a growing community of researchers has emerged around the use of constraint-based reconstruction and analysis (COBRA) methods to simulate, analyze and predict a variety of metabolic phenotypes using genome-scale models. The COBRA Toolbox, a MATLAB package for implementing COBRA methods, was presented earlier. Here we present a substantial update of this in silico toolbox. Version 2.0 of the COBRA Toolbox expands the scope of computations by including in silico analysis methods developed since its original release. New functions include (i) network gap filling, (ii) (13)C analysis, (iii) metabolic engineering, (iv) omics-guided analysis and (v) visualization. As with the first version, the COBRA Toolbox reads and writes systems biology markup language-formatted models. In version 2.0, we improved performance, usability and the level of documentation. A suite of test scripts can now be used to learn the core functionality of the toolbox and validate results. This toolbox lowers the barrier of entry to use powerful COBRA methods.
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              The effects of alternate optimal solutions in constraint-based genome-scale metabolic models.

              Genome-scale constraint-based models of several organisms have now been constructed and are being used for model driven research. A key issue that may arise in the use of such models is the existence of alternate optimal solutions wherein the same maximal objective (e.g., growth rate) can be achieved through different flux distributions. Herein, we investigate the effects that alternate optimal solutions may have on the predicted range of flux values calculated using currently practiced linear (LP) and quadratic programming (QP) methods. An efficient LP-based strategy is described to calculate the range of flux variability that can be present in order to achieve optimal as well as suboptimal objective states. Sample results are provided for growth predictions of E. coli using glucose, acetate, and lactate as carbon substrates. These results demonstrate the extent of flux variability to be highly dependent on environmental conditions and network composition. In addition we examined the impact of alternate optima for growth under gene knockout conditions as calculated using QP-based methods. It was observed that calculations using QP-based methods can show significant variation in growth rate if the flux variability among alternate optima is high. The underlying biological significance and general source of such flux variability is further investigated through the identification of redundancies in the network (equivalent reaction sets) that lead to alternate solutions. Collectively, these results illustrate the variability inherent in metabolic flux distributions and the possible implications of this heterogeneity for constraint-based modeling approaches. These methods also provide an efficient and robust method to calculate the range of flux distributions that can be derived from quantitative fermentation data.
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                Author and article information

                Contributors
                Journal
                BMC Syst Biol
                BMC Syst Biol
                BMC Systems Biology
                BioMed Central
                1752-0509
                2013
                8 August 2013
                : 7
                : 74
                Affiliations
                [1 ]Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive MC0412, La Jolla, 92093-0412, CA, USA
                [2 ]Biological Engineering Department, Utah State University, 4105 Old Main Hill, Logan, UT 84322-4105, USA
                Article
                1752-0509-7-74
                10.1186/1752-0509-7-74
                3751080
                23927696
                7a1ee2d4-2d69-4a89-9830-112a7939f079
                Copyright © 2013 Ebrahim et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 August 2012
                : 2 August 2013
                Categories
                Software

                Quantitative & Systems biology
                genome-scale,network reconstruction,metabolism,gene expression,constraint-based modeling

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