Ogbu, Henry Nwagu and Covenant University, Theses (2021) DISCOVERY OF HIDDEN PATHWAYS IN PROTEIN NETWORK FOR DIABETES THERAPEUTIC ADVANCES AND TREATMENT. Masters thesis, Covenant University Ota..
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Abstract
Diabetes is one of the world's deadliest diseases caused when the pancreas cannot produce the insulin required by the body to regulate the amount of sugar. Several attempts have been made to produce drugs that would be used to cure diabetes, but to no avail, and it has no cure as of today. Several experimental methods have been applied in the drug discovery process, but they are very slow, more expensive, and environmentally dependent. This study computationally modelled a protein-protein interaction network to identify pathways to diabetes disease that might be useful in the drug discovery process. This work was done with Cytoscape and Bioconductor package of R language. The differentially expressed genes (DEGs) were used to construct the protein-protein interaction network with STRING using k-means clustering. High confidence of 0.9 was used as a threshold for interacting proteins, and the network was further visualized and analysed for degree and betweenness centrality with centiscape, a plugin of Cytoscape 3.8.2. G: profiler was used to perform network enrichment so that similar genes were clustered together and a list of the most enriched pathways were found, and Cytoscape was used to discover, analyse, annotate and visualize the pathways associated with core genes in the diabetic network. The analysis from Cytoscape showed that Aquarius intron-binding spliceosomal factor, pre-mRNA processing factor 19 and XPA binding protein as the three genes that came out with the highest degree centrality score of 29 from the network interactions. However, the SNW domain containing 1 (SNW1) gene had the highest betweenness centrality score of approximately 1008 and a degree centrality of about 90% of the maximum score. Consequently, the significantly common pathways among all the involved genes as ranked by g: profiler using their adjusted p-value include mRNA splicing-major pathway, mRNA splicing, and processing capped intron-containing pre-mRNA pathways. Therefore, this study recommends that the significantly common pathways in the AQR, XAB2, PRPF19 and SNW1 genes be considered a possible drug target to seek solutions to diabetes Type 2.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | Diabetes Mellitus, Protein-Protein Interaction (PPI), Protein Interaction Network (PIN), Differentially Expressed Genes (DEGs), Pathway Enrichment Analysis. |
| Subjects: | Q Science > QA Mathematics Q Science > QA Mathematics > QA76 Computer software |
| Divisions: | Faculty of Engineering, Science and Mathematics > School of Electronics and Computer Science |
| Depositing User: | Mrs Patricia Nwokealisi |
| Date Deposited: | 11 Nov 2021 07:45 |
| Last Modified: | 11 Nov 2021 07:45 |
| URI: | http://eprints.covenantuniversity.edu.ng/id/eprint/15464 |
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