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Computational Prediction of Essential Metabolic Genes Using Constraint-Based Approaches

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Gene Essentiality

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1279))

Abstract

In this chapter, we describe the application of constraint-based modeling to predict the impact of gene deletions on a metabolic phenotype. The metabolic reactions taking place inside cells form large networks, which have been reconstructed at a genome-scale for several organisms at increasing levels of detail. By integrating mathematical modeling techniques with biochemical principles, constraint-based approaches enable predictions of metabolite fluxes and growth under specific environmental conditions or for genetically modified microorganisms. Similar to the experimental knockout of a gene, predicting the essentiality of a metabolic gene for a phenotype further allows to generate hypotheses on its biological function and design of genetic engineering strategies for biotechnological applications. Here, we summarize the principles of constraint-based approaches and provide a detailed description of the procedure to predict the essentiality of metabolic genes with respect to a specific metabolic function. We exemplify the approach by predicting the essentiality of reactions in the citric acid cycle for the production of glucose from fatty acids.

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Acknowledgement

I thank Tino Krell and Juan Luis Ramos for critical reading of the manuscript. This research was supported by a Marie Curie Intra-European Fellowship within the 7th European Community Framework Programme.

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  1. Department of Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas (CSIC), Profesor Albareda 1, 18008, Granada, Spain

    Georg Basler

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  1. Georg Basler
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Correspondence to Georg Basler .

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  1. Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA

    Long Jason Lu

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Basler, G. (2015). Computational Prediction of Essential Metabolic Genes Using Constraint-Based Approaches. In: Lu, L. (eds) Gene Essentiality. Methods in Molecular Biology, vol 1279. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2398-4_12

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  • DOI: https://doi.org/10.1007/978-1-4939-2398-4_12

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