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Bhak, Jong
KOrean GenomIcs Center(KOGIC)
Research Interests
  • Geromics, genomics, bioinformatics, protein Engineering, OMICS

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Protein network prediction and topological analysis in Leishmania major as a tool for drug target selection

Cited 22 times inthomson ciCited 30 times inthomson ci
Title
Protein network prediction and topological analysis in Leishmania major as a tool for drug target selection
Author
Florez, Andres F.Park, DaeuiBhak, Jong HwaKim, Byoung-ChulKuchinsky, AllanMorris, John H.Espinosa, JairoMuskus, Carlos
Keywords
Betweenness centrality; Biological process; Computational approach; Experimental validations; Parasitic infections; Potential drug targets; Protein interaction networks; Topological analysis
Issue Date
2010-09
Publisher
BIOMED CENTRAL LTD
Citation
BMC BIOINFORMATICS, v.11, no., pp. -
Abstract
Background: Leishmaniasis is a virulent parasitic infection that causes a worldwide disease burden. Most treatments have toxic side-effects and efficacy has decreased due to the emergence of resistant strains. The outlook is worsened by the absence of promising drug targets for this disease. We have taken a computational approach to the detection of new drug targets, which may become an effective strategy for the discovery of new drugs for this tropical disease.Results: We have predicted the protein interaction network of Leishmania major by using three validated methods: PSIMAP, PEIMAP, and iPfam. Combining the results from these methods, we calculated a high confidence network (confidence score > 0.70) with 1,366 nodes and 33,861 interactions. We were able to predict the biological process for 263 interacting proteins by doing enrichment analysis of the clusters detected. Analyzing the topology of the network with metrics such as connectivity and betweenness centrality, we detected 142 potential drug targets after homology filtering with the human proteome. Further experiments can be done to validate these targets.Conclusion: We have constructed the first protein interaction network of the Leishmania major parasite by using a computational approach. The topological analysis of the protein network enabled us to identify a set of candidate proteins that may be both (1) essential for parasite survival and (2) without human orthologs. These potential targets are promising for further experimental validation. This strategy, if validated, may augment established drug discovery methodologies, for this and possibly other tropical diseases, with a relatively low additional investment of time and resources.
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DOI
10.1186/1471-2105-11-484
ISSN
1471-2105
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BME_Journal Papers
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