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Bioinformatics
Article . 2006 . Peer-reviewed
Data sources: Crossref
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Bioinformatics
Article
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Bioinformatics
Article . 2006
DBLP
Article . 2020
Data sources: DBLP
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Observing local and global properties of metabolic pathways: ‘load points’ and ‘choke points’ in the metabolic networks

Authors: Syed Asad Rahman; Dietmar Schomburg;

Observing local and global properties of metabolic pathways: ‘load points’ and ‘choke points’ in the metabolic networks

Abstract

Abstract Motivation: The local and global aspects of metabolic network analyses allow us to identify enzymes or reactions that are crucial for the survival of the organism(s), therefore directing us towards the discovery of potential drug targets. Results: We demonstrate a new method (‘load points’) to rank the enzymes/metabolites in the metabolic network and propose a model to determine and rank the biochemical lethality in metabolic networks (enzymes/metabolites) through ‘choke points’. Based on an extended form of the graph theory model of metabolic networks, metabolite structural information was used to calculate the k-shortest paths between metabolites (the presence of more than one competing path between substrate and product). On the basis of these paths and connectivity information, load points were calculated and used to empirically rank the importance of metabolites/enzymes in the metabolic network. The load point analysis emphasizes the role that the biochemical structure of a metabolite, rather than its connectivity (hubs), plays in the conversion pathway. In order to identify potential drug targets (based on the biochemical lethality of metabolic networks), the concept of choke points and load points was used to find enzymes (edges) which uniquely consume or produce a particular metabolite (nodes). A non-pathogenic bacterial strain Bacillus subtilis 168 (lactic acid producing bacteria) and a related pathogenic bacterial strain Bacillus anthracis Sterne (avirulent but toxigenic strain, producing the toxin Anthrax) were selected as model organisms. The choke point strategy was implemented on the pathogen bacterial network of B.anthracis Sterne. Potential drug targets are proposed based on the analysis of the top 10 choke points in the bacterial network. A comparative study between the reported top 10 bacterial choke points and the human metabolic network was performed. Further biological inferences were made on results obtained by performing a homology search against the human genome. Availability: The load and choke point modules are introduced in the Pathway Hunter Tool (PHT), the basic version of which is available on Contact: d.schomburg@uni-koeln.de Supplementary information: Supplementary data are available on Bioinformatics online.

Related Organizations
Keywords

Metabolism, Bacterial Proteins, Multienzyme Complexes, Bacillus, Computer Simulation, Models, Biological, Signal Transduction

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    popularity
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    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
91
Top 10%
Top 10%
Top 10%
gold