Evidence map›Paper›PMID 38701067›Full record

ArticlePLoS neglected tropical diseases2024

Transcriptome profiles of Trypanosoma brucei rhodesiense in Malawi reveal focus specific gene expression profiles associated with pathology.

Peter Nambala, Harry Noyes, Joyce Namulondo, Oscar Nyangiri, Vincent Pius Alibu, Barbara Nerima, Annette MacLeod, Enock Matovu, Janelisa Musaya, Julius Mulindwa and 1 more

Abstract read
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Article in PLoS neglected tropical diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Peter NambalaDepartment of Biochemistry and Sports Sciences, College of Natural Sciences, Makerere University, Kampala, Uganda.
Harry NoyesCentre for Genomic Research, University of Liverpool, Liverpool, United Kingdom.
Joyce NamulondoDepartment of Biotechnical and Diagnostic Sciences, College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, Uganda.
Oscar NyangiriDepartment of Biotechnical and Diagnostic Sciences, College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, Uganda.
Vincent Pius AlibuDepartment of Biotechnical and Diagnostic Sciences, College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, Uganda.
Barbara NerimaDepartment of Biochemistry and Sports Sciences, College of Natural Sciences, Makerere University, Kampala, Uganda.
Annette MacLeodWellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom.
Enock MatovuDepartment of Biotechnical and Diagnostic Sciences, College of Veterinary Medicine Animal Resources and Biosecurity, Makerere University, Kampala, Uganda.
Janelisa MusayaKamuzu University of Health Sciences, Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Julius MulindwaDepartment of Biochemistry and Sports Sciences, College of Natural Sciences, Makerere University, Kampala, Uganda.ORCID 0000-0002-5419-2760
TrypanoGEN+ Research Group as Members of the H3Africa Consortium

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundSleeping sickness caused by Trypanosoma brucei rhodesiense is a fatal disease and endemic in Southern and Eastern Africa. There is an urgent need to develop novel diagnostic and control tools to achieve elimination of rhodesiense sleeping sickness which might be achieved through a better understanding of trypanosome gene expression and genetics using endemic isolates. Here, we describe transcriptome profiles and population structure of endemic T. b. rhodesiense isolates in human blood in Malawi. METHODOLOGY: Blood samples of r-HAT cases from Nkhotakota and Rumphi foci were collected in PaxGene tubes for RNA extraction before initiation of r-HAT treatment. 100 million reads were obtained per sample, reads were initially mapped to the human genome reference GRCh38 using HiSat2 and then the unmapped reads were mapped against Trypanosoma brucei reference transcriptome (TriTrypDB54_TbruceiTREU927) using HiSat2. Differential gene expression analysis was done using the DeSeq2 package in R. SNP calling from reads that were mapped to the T. brucei genome was done using GATK in order to identify T.b. rhodesiense population structure.

results24 samples were collected from r-HAT cases of which 8 were from Rumphi and 16 from Nkhotakota foci. The isolates from Nkhotakota were enriched with transcripts for cell cycle arrest and stumpy form markers, whereas isolates in Rumphi focus were enriched with transcripts for folate biosynthesis and antigenic variation pathways. These parasite focus-specific transcriptome profiles are consistent with the more virulent disease observed in Rumphi and a less symptomatic disease in Nkhotakota associated with the non-dividing stumpy form. Interestingly, the Malawi T.b. rhodesiense isolates expressed genes enriched for reduced cell proliferation compared to the Uganda T.b. rhodesiense isolates. PCA analysis using SNPs called from the RNAseq data showed that T. b. rhodesiense parasites from Nkhotakota are genetically distinct from those collected in Rumphi.

conclusionOur results suggest that the differences in disease presentation in the two foci is mainly driven by genetic differences in the parasites in the two major endemic foci of Rumphi and Nkhotakota rather than differences in the environment or host response.

Indexed as

TranscriptomeTrypanosoma brucei rhodesienseTrypanosomiasis, AfricanGene Expression ProfilingHumansMalawiMalePolymorphism, Single Nucleotide

Identifiers

PMID38701067
PMCPMC11095692

What Socratic holds

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LicenceCC BY
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.