Abstract
BackgroundTrypanosoma brucei species are motile protozoan parasites that are cyclically transmitted by tsetse fly (genus Glossina) causing human sleeping sickness and nagana in livestock in sub-Saharan Africa. African trypanosomes display digenetic life cycle stages in the tsetse fly vector and in their mammalian host. Experimental work on insect-stage trypanosomes is challenging because of the difficulty in setting up successful in vitro cultures. Therefore, there is limited knowledge on the trypanosome biology during its development in the tsetse fly. Consequently, this limits the development of new strategies for blocking parasite transmission in the tsetse fly.MethodsIn this study, RNA-Seq data of insect-stage trypanosomes were used to construct a T. brucei gene co-expression network using the weighted gene co-expression analysis (WGCNA) method. The study identified significant enriched modules for genes that play key roles during the parasite’s development in tsetse fly. Furthermore, potential 3′ untranslated region (UTR) regulatory elements for genes that clustered in the same module were identified using the Finding Informative Regulatory Elements (FIRE) tool.ResultsA fraction of gene modules (12 out of 27 modules) in the constructed network were found to be enriched in functional roles associated with the cell division, protein biosynthesis, mitochondrion, and cell surface. Additionally, 12 hub genes encoding proteins such as RNA-binding protein 6 (RBP6), arginine kinase 1 (AK1), brucei alanine-rich protein (BARP), among others, were identified for the 12 significantly enriched gene modules. In addition, the potential regulatory elements located in the 3′ untranslated regions of genes within the same module were predicted.ConclusionsThe constructed gene co-expression network provides a useful resource for network-based data mining to identify candidate genes for functional studies. This will enhance understanding of the molecular mechanisms that underlie important biological processes during parasite’s development in tsetse fly. Ultimately, these findings will be key in the identification of potential molecular targets for disease control.Graphical
Highlights
Trypanosoma brucei species are motile protozoan parasites that are cyclically transmitted by tsetse fly causing human sleeping sickness and nagana in livestock in sub-Saharan Africa
In contrast to a T. brucei gene co-expression network generated from a previous study for procyclic and bloodstream forms using microarray data [20], our study focused on the insect stage morphological forms of the parasite by analyzing RNA-Seq data
Construction of the T. brucei gene co-expression network provides a valuable resource for identifying candidate genes for experimental work
Summary
Trypanosoma brucei species are motile protozoan parasites that are cyclically transmitted by tsetse fly (genus Glossina) causing human sleeping sickness and nagana in livestock in sub-Saharan Africa. The morphological forms are Mwangi et al Parasites Vectors (2021) 14:74 the biology of a trypanosome during its development in the vector—the life cycle phase referred to as “the heart of darkness” [6]. The knowledge of trypanosome development in the tsetse fly will contribute to efforts towards interrupting disease transmission by the vector This can be achieved through targeted disruption of the parasite’s essential molecular processes such as motility, regulation of differentiation, morphological remodeling, and signal transduction [7, 8]. RNA-Seq technology has been a fundamental tool for studying gene expression profiles of T. brucei and other kinetoplastids with an aim of expanding knowledge on their biology [9] This is because RNA-Seq provides a comprehensive and more accurate transcriptome quantification and characterization compared to the hybridization-based techniques such as microarray [10]. In addition to identification of differentially expressed genes, transcriptome data could be used to create gene co-expression networks which provide a functional and molecular understanding of key biological processes in an organism [11, 12]
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