Estudo da interação plasmodium-hospedeiro via meta-análise de dados públicos de sequenciamento duplo de RNA

• Autor(a) principal: Silva, Bárbara Fernandes da
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/12996
• topic: Malária; RNA-seq duplo; Integração de dados; Imunidade inata; Dual RNA-seq; Data integration; Innate immunity; CIENCIAS BIOLOGICAS::PARASITOLOGIA::ENTOMOLOGIA E MALACOLOGIA DE PARASITOS E VETORES

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.