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. 2016 Sep 12;10(9):e0004965.
doi: 10.1371/journal.pntd.0004965. eCollection 2016 Sep.

DenHunt - A Comprehensive Database of the Intricate Network of Dengue-Human Interactions

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Free PMC article

DenHunt - A Comprehensive Database of the Intricate Network of Dengue-Human Interactions

Prashanthi Karyala et al. PLoS Negl Trop Dis. .
Free PMC article

Abstract

Dengue virus (DENV) is a human pathogen and its etiology has been widely established. There are many interactions between DENV and human proteins that have been reported in literature. However, no publicly accessible resource for efficiently retrieving the information is yet available. In this study, we mined all publicly available dengue-human interactions that have been reported in the literature into a database called DenHunt. We retrieved 682 direct interactions of human proteins with dengue viral components, 382 indirect interactions and 4120 differentially expressed human genes in dengue infected cell lines and patients. We have illustrated the importance of DenHunt by mapping the dengue-human interactions on to the host interactome and observed that the virus targets multiple host functional complexes of important cellular processes such as metabolism, immune system and signaling pathways suggesting a potential role of these interactions in viral pathogenesis. We also observed that 7 percent of the dengue virus interacting human proteins are also associated with other infectious and non-infectious diseases. Finally, the understanding that comes from such analyses could be used to design better strategies to counteract the diseases caused by dengue virus. The whole dataset has been catalogued in a searchable database, called DenHunt (http://proline.biochem.iisc.ernet.in/DenHunt/).

Conflict of interest statement

The authors have declared that no competing interests exist. LS is an employee of LifeIntelect Consultancy Pvt Ltd. and has declared that no competing interests exists.

Figures

Fig 1
Fig 1. Visualization of the network of direct dengue-human interactions.
The network of direct physical interactions of dengue–human components was visualized using Cytoscape. Pink hexagons represent dengue viral components, blue circles represent human proteins that interact with one dengue component and green circles represent human proteins that interact with more than one dengue protein.
Fig 2
Fig 2. Enrichment of KEGG pathways for the dengue virus interacting human proteins.
Pathway enrichment analysis for dengue virus interacting proteins was carried out using WebGestalt. Only pathways that have 3 and more dengue virus interacting proteins and an adj p-value of ≤ 0.01 are selected. The KEGG pathways that were enriched were grouped into broad categories as mentioned in the KEGG pathway database. (a) The broad categories and their total number of dengue virus interacting human proteins are plotted as a pie chart. The color code for each category is given below the pie chart. Pathways that have 20 and more dengue virus interacting proteins belonging to the top 4 broad categories are plotted as bar graph where (b) represents immune system pathways, (c) represents signal transduction pathways, (d) represents transport and catabolism and (e) represents metabolic pathways. In all cases numbers indicates the number of genes identified in each pathway.
Fig 3
Fig 3. Representation of dengue viral interacting proteins in NF-κB and RIG-I-like receptor signaling pathway.
The dengue virus interacting proteins are mapped to the KEGG pathways using the “Search&Colour Pathway” tool from the KEGG database. The proteins that are involved in direct interactions are colored orange, indirect interactions are colored in pink, up-regulated proteins are colored red and down-regulated proteins are colored green. The viral components are depicted as blue hexagons. Fig 3a represents NF-κB and 3b RIG-I-like receptor signaling pathway.
Fig 4
Fig 4. Association of dengue viral interacting human proteins with infectious diseases and non-infectious diseases.
The dengue virus interacting human proteins and their associated a) infectious and b) non-infectious diseases are visualized as a network using Cytoscape. The diseases are represented as triangles and are color coded based on the disease group they belong to. The genes that are associated with only in one disease are represented as violet colored circles and those that are associated with more than one disease are represented as green colored circles. c) Pathway analysis of the dengue virus interacting proteins that are associated with both infectious and non-infectious diseases. KEGG pathways that had 20 or more dengue virus proteins associated with both infectious and non-infectious diseases using KEGG Mapper—Search Pathway is shown as a bar graph.

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Grant support

The authors received no specific funding for this work.
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