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Murungi, E.

Publications and source records attributed to Murungi, E..

4 recordsLinked to original sources

Computational Prediction of Plasmodium falciparum Antigen-T-cell Receptor Interactions via Molecular Docking: Implications for Malaria Vaccine Design

Malaria is one of the deadliest diseases in sub-Saharan Africa and Southeast Asia. The majority of the fatalities occur mostly in children under 5 years and pregnant women and this is due to infection by Plasmodium spp, of which Plasmodium falciparum is the most virulent and is responsible for most of the morbidity and mortality. Despite various public health interventions such as use of insecticide-treated bed nets, spraying of homes with insecticides and use of WHO recommended artemisinin-based combination therapies (ACT), malaria prevention still faces major setback due to drug and insecticide resistance by P. falciparum and mosquitoes respectively. The study uses molecular docking and immunoinformatics to screen various Plasmodium spp antigens and evaluate their antigenicity and suitability as vaccine candidates. The P. falciparum antigens and T-cell receptor (TCR) structures were obtained from Protein Data Bank (PDB) based on a range of factors related to their role in the lifecycle of the parasite and their status as vaccine targets. Protein structures not available in the PDB were predicted using AlphaFold. The 3D structures of selected P. falciparum antigens and TCR structures were downloaded in PDB format then all water molecules, Hetatm, and bound ligands were deleted from the protein structures using BIOVIA Discovery Studio Visualizer. Subsequently, molecular docking was done using ClusPro v2.0 server and docked complexes were compared. The findings of this study gave valuable insights into the interaction of human immune response with P. falciparum antigens. The best three ranked antigen complexes are PfCyRPA, PfMSP10 and PfCSP and this confirm their use as potential candidates for vaccine development. This study highlights the usefulness of computational docking in identifying P. falciparum antigens of excellent immunogenic potential as vaccine candidates.

bioinformatics↗

Chromosome-scale assembly of the African yam bean genome

Genomics-informed breeding of locally adapted, nutritious, albeit underutilised African crops can help mitigate food and nutrition insecurity challenges in Africa, particularly against the backdrop of climate change. However, utilisation of modern crop improvement tools including genomic selection and genome editing for many African indigenous crops is hampered by the scarcity of genetic and genomic resources. Here we report on the assembly of the genome of African yam bean (Sphenostylis stenocarpa), a tuberous legume crop that is indigenous to Africa. By combining long and short read sequencing with Hi-C scaffolding, we produced a chromosome-scale assembly with an N50 of 69.5 Mbp and totalling 649 Mbp in length (77 - 81% of the estimated genome size based on flow cytometry). Using transcriptome evidence from Nanopore RNA-Seq and homology evidence from related crops, we annotated 31,614 putative protein coding genes. We further show how this resource improves anchoring of markers, genome-wide association analysis and candidate gene analyses in Africa yam bean. This genome assembly provides a valuable resource for genetic research in Africa yam bean.

genomics↗

Inference of Rift Valley Fever pathogenesis in Bos taurus using a gene co-expression network

BackgroundRift Valley Fever (RVF) is a viral disease caused by the Rift Valley Fever virus and spread mainly by the Aedes and Culex mosquito species. The disease primarily infects domestic animals such as sheep, goats, and cattle, resulting in a spectrum of clinical outcomes including morbidity, massive storm abortions, and neonatal fatalities. RVF outbreaks are closely linked to above-average rainfall and flooding, which create an ideal environment for mosquitos to breed, multiply, and transmit the virus to animals. The outcomes of human RVF infection range from self-limiting febrile illness to potentially fatal hemorrhagic diatheses and miscarriage in pregnant women. Collectively, the economic losses due to the zoonotic RVF disease is immense. MethodsUsing the Weighted Gene Co-expression Network Analysis (WGCNA) package, RNA-Seq data generated from five healthy Bos taurus steer calves aged 4-6 months was obtained from the Gene Expression Omnibus (GEO) database (Accession number GSE71417). The data was utilized to construct a gene co-expression network. Enriched modules containing genes potentially involved in RVF infection progression were identified. Moreover, using the Multiple Expectation Maximizations for Motif Elicitation (MEME) suite, consensus regulatory motifs of enriched gene clusters were deciphered and the most abundant putative regulatory motif in each enriched module unveiled by comparative analysis with publicly available motifs using the TOMTOM motif comparison tool. The potential roles of the identified regulatory motifs were inferred by literature mining. ResultsThe constructed gene co-expression network revealed thirty-three (33) modules, nine of which were enriched for Gene Ontology terms linked to RVF pathogenesis. Functional enrichment in two (red and turquoise) of the nine modules was significant. ASH1-like histone lysine methyltransferase and Astrotactin were the hub genes for the red and turquoise modules respectively. ASH1-like histone lysine methyltransferase gene is involved in chromatin epigenetic modification while Astrotactin is a vertebrate-specific gene that plays an important role in neurodevelopment. Additionally, consensus regulatory motifs located on the 3' end of genes in each enriched module was identified. ConclusionsIn this study, we have developed a gene co-expression network that has aided in the unveiling of functionally related genes, intramodular hub genes, and immunity genes potentially involved in RVF pathogenesis. The discovery of functional genes with putative critical roles in the establishment of RVF infection establishment will contribute to the understanding of the molecular mechanism of RVF pathogenesis. Importantly, the putative regulatory motifs identified are plausible targets for RVF drug and vaccine development.

systems biology↗

Title: Potentially zoonotic gastrointestinal nematodes co-infecting free ranging non-human primates in Kenyan urban centres

BackgroundNatural infections with soil transmitted nematodes occur in non-human primates (NHPs) and have the potential to cross primate-species boundaries and cause diseases of significant public health concern. Despite their presence in most urban centres in Kenya, comprehensive studies on their gastrointestinal parasites are scant. ObjectiveConduct a cross-sectional survey to identify zoonotic nematodes in free-ranging NHPs found within four selected urban and peri-urban centres in Kenya. MethodsA total of 86 NHPs: 41 African green monkeys [AGM] (Chlorocebus aethiops), 30 olive baboons (Papio anubis), 5 blue monkeys (Cercopithecus mitis stuhlmanni) and 10 red tailed monkeys (Cercopithecus ascanius) were sampled once in situ and released back to their habitat. Microscopy was used to identify nematodes egg and larvae stages in the samples. Subsequently, PCR coupled with high-resolution melting (PCR-HRM) analysis and sequencing were used to identify nodule worms. ResultsNHPs inhabiting densely populated urban environs in Kenya were found infected with a rich diversity of nematodes including three potentially zoonotic nematodes including Oesophagostomum stephanostomum, Oesophagostomum bifurcum and Trichostrongylus colubriformis and co-infections were common. ConclusionPhylogenetic analysis showed that O. stephanostomum from red tailed and blue monkeys have a close evolutionary relatedness to human isolates suggesting the zoonotic potential of this parasite. Moreover, we also report the first natural co-infection of O. bifurcum and O. stephanostomum in free-ranging AGMs.

zoology↗