In silico-aided molecular identification of potential pathogenic and prognostic differentially expressed genes (DEGs) associated with human trypanosomiasis

Abstract

Background: The molecular mechanism of human African trypanosomiasis remains to be fully understood. It is urgently required to identify genes that are associated with trypanosome development and prognosis and to elucidate the underlying molecular mechanisms. In the present study, we aimed to identify potential pathogenic and prognostic differentially expressed genes (DEGs) associated with human trypanosomiasis through bioinformatics analysis of genetic profiles from infected patients. Methods: The gene expression dataset of trypanosome infected (GSE85996) patients were obtained from the Gene Expression Omnibus (GEO). DEGs were identified using the LIMMA Package of R. The GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses were conducted through Enrich. The protein-protein interaction (PPI) network of the DEGs was established through the STRING (Search Tool for the Retrieval of Interacting Genes database) server. Results: A total of 20 differentially expressed genes including 3 upregulated genes (STAT1, FBXW17 and LRRC15), and 17 downregulated genes (Setbp1, Rxfp1, 5031414D18Rik, Dnm3os, Rxfp1, Serpine2, Rnase2a, Tnfaip8l3, Serpine2, Adap1, Nrg1, P2ry14, Vegfd, Aldh1a2, P2ry14, Fgfbp3 and Aldh1a2) were identified. The PPI network of the DEG identified a total of 40 nodes, 254 edges, 12.7 average node degree, and a PPI enrichment p-value of < 1.0e-16. The enriched KEGG pathway of the DEG includes; Relaxin signalling pathway, retinol metabolism, erbb signalling pathway, neuroactive ligand-receptor interaction, TNF signalling pathway, and focal adhesion. However, the enriched GO were r FGFR signalling pathway, cardiac endothelial cell differentiation, cardiac muscle cell myoblast differentiation, plasminogen activation, mast cell chemotaxis, endocardial cell differentiation, and transmembrane receptor protein tyrosine kinase. Conclusion: The present study may provide a basis for an improved understanding of trypanosome infection in humans. The DEGs identified in this study could be utilized as new biomarkers for prognosis and potential new targets for the development of new drugs against human trypanosomiasis.