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

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Title
Protein network prediction and topological analysis in Leishmania major as a tool for drug target selection
Author(s)
F F Florez; Dae Ui Park; Jong Hwa Park; Byung Chul Kim; A Kuchinsky; J H Morris; J Espinosa; C Muskus
Bibliographic Citation
BMC Bioinformatics, vol. 11, pp. 484-484
Publication Year
2010
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.
ISSN
1471-2105
Publisher
Springer-BMC
DOI
http://dx.doi.org/10.1186/1471-2105-11-484
Type
Article
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1. Journal Articles > Journal Articles
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