SHEKARI, ABEDNEGO and Covenant University, Theses (2023) ANALYSIS OF THE ANOPHELES GAMBIAE INSECTICIDE RESISTANCE PROTEIN-PROTEIN INTERACTION NETWORK. Masters thesis, COVENANT UNIVERSITY.
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Abstract
One of the deadliest diseases affecting millions of people annually, particularly in Africa, and has claimed millions of lives is malaria. It is caused by the malaria pathogen Plasmodium falciparum, during a blood meal by a female Anopheles vector. Although several control programs were established to enable the effective control and management of the disease by targeting the malaria vector using insecticides, there has been an increase in resistance to the currently existing insecticides. One of the challenges in effectively controlling malaria is because the molecular mechanisms by which malaria vector evades insecticide effect remain unclear. This could have enabled the development of target-specific insecticides. This study aims to elucidate the complex underlying mechanisms Anopheles gambiae evade currently existing insecticides. The An. gambiae PPIN was constructed using Cytoscape, and topology and clustering analysis was conducted to predict key proteins and pathways that are significant in the molecular mechanisms of An. gambiae. The network's GO and KEGG enrichment analysis was conducted using DAVID. RStudio was used to visualize the network. The network consists of 224 proteins (nodes) and 2115 interactions (edges). The network topology analysis reveals three essential proteins (GSTE2, AGAP002945, and AGAP004581) that are hub genes, and when either of them is removed, the network will crash. The GO and KEGG analysis showed three important biological processes (glutathione metabolism, protein folding and refolding, and chaperone-mediated protein folding) and three pathways (cytochrome P450s, glutathione, and protein processing pathways) were significantly enriched in the vector's insecticide resistance molecular mechanisms. The analysis showed that the proteins associated with insecticide resistance in An. gambiae were confined with the cytoplasm, cytosol, and plasma membrane. From the Study, five essential candidate target proteins (GSTE1, GSTE2, GSTD3, AGAP002945, and AGAP004581) and three molecular pathways (cytochrome P450s, glutathione, and protein processing pathways) were found to be enriched in An. gambiae. It is anticipated that this will guide future research into developing novel target-specific insecticides to combat malaria.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | Insecticide resistance, Protein-protein interaction network, Centrality analysis, Clustering analysis, Anopheles gambiae |
| Subjects: | Q Science > Q Science (General) Q Science > QA Mathematics > QA75 Electronic computers. Computer science Q Science > QH Natural history > QH301 Biology |
| Divisions: | Faculty of Engineering, Science and Mathematics > School of Electronics and Computer Science |
| Depositing User: | AKINWUMI |
| Date Deposited: | 11 Jul 2023 16:17 |
| Last Modified: | 11 Jul 2023 16:17 |
| URI: | http://eprints.covenantuniversity.edu.ng/id/eprint/17168 |
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