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Strategies for efficient disruption of metabolism in Mycobacterium tuberculosis from network analysis

Raman, Karthik and Vashisht, Rohit and Chandra, Nagasuma (2009) Strategies for efficient disruption of metabolism in Mycobacterium tuberculosis from network analysis. In: Molecular BioSystems, 5 (12). pp. 1740-1751.

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Abstract

Tuberculosis continues to be a major health challenge, warranting the need for newer strategies for therapeutic intervention and newer approaches to discover them. Here, we report the identification of efficient metabolism disruption strategies by analysis of a reactome network. Protein-protein dependencies at a genome scale are derived from the curated metabolic network, from which insights into the nature and extent of inter-protein and inter-pathway dependencies have been obtained. A functional distance matrix and a subsequent nearness index derived from this information, helps in understanding how the influence of a given protein can pervade to the metabolic network. Thus, the nearness index can be viewed as a metabolic disruptability index, which suggests possible strategies for achieving maximal metabolic disruption by inhibition of the least number of proteins. A greedy approach has been used to identify the most influential singleton, and its combination with the other most pervasive proteins to obtain highly influential pairs, triplets and quadruplets. The effect of deletion of these combinations on cellular metabolism has been studied by flux balance analysis. An obvious outcome of this study is a rational identification of drug targets, to efficiently bring down mycobacterial metabolism.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to Royal Society of Chemistry.
Department/Centre: Division of Information Sciences > Supercomputer Education & Research Centre
Division of Information Sciences > BioInformatics Centre
Date Deposited: 03 Dec 2009 08:57
Last Modified: 19 Sep 2010 05:53
URI: http://eprints.iisc.ernet.in/id/eprint/25052

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