Estudo da interação plasmodium-hospedeiro via meta-análise de dados públicos de sequenciamento duplo de RNA
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2023-06-29
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Universidade Federal de Goiás
Resumo
Malaria is a potentially fatal disease caused by Plasmodium parasites
transmitted by Anopheles mosquitoes. Infection causes an intense inflammatory response,
but the molecular mechanisms of interaction between host and parasite remain largely
unknown. Although many studies have been dedicated to understanding the host immune
response using RNA sequencing of whole blood from malaria patients, technological
advances have enabled an integrative evaluation of both host and parasite transcriptomes.
The accumulation of different datasets in public repositories provides an opportunity to
uncover the interaction between host and Plasmodium via integrative data analysis.
Methods. We evaluated whole blood RNA-seq data from 8 different datasets of
individuals with malaria caused by infection with Plasmodium falciparum (Pf). The
transcriptomes from humans were transformed to Blood Transcriptional Modules (BTM).
Spearman´s correlation method was used to evaluated associations between BTMs and
Pf genes. PlasmoDB platform was used to evaluate Pf genes. Results Initially, we
selected correlations (p < 0.001) conserved in 60% of the datasets to generate a hostparasite transcriptional network composed, for exemplo, of BTMs related to the
activation and response of dendritic cells and myeloid cells, besides of leukocyte
differentiation and NK cells. Later, we selected correlations conserved in 75% of the
datasets, which revealed a host-parasite transcriptional sub network, in which BTMs are
related to monocytes, activation of innate immunity, as well as regulation of
inflammation. Moreover, the comparison between the activity of BTMs included in this
sub network between individuals with malaria and healthy controls demonstrated the
downregulation of genes involved with SMAD2/3 signaling and transcriptional targets of
glucocorticoid receptor, while the other BTMs were upregulated, including modules
related to monocytes and signaling by TLR, RIG-I and cytosolic DNA sensors.
Conclusion. In conclusion, our study identified diverse associations between genes of P.
falciparum and gene modules reflecting cells and processes of the human immune
response that can be prioritized in experimental assays.
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SILVA, B. F. Estudo da interação plasmodium-hospedeiro via meta-análise de dados públicos de sequenciamento duplo de RNA. 2023. 52 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2023.