Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Dual RNA-seq of peripheral blood from Gambian children with severe or uncomplicated Plasmodium falciparum malaria

ABSTRACT: This study examined the differences in human and parasite gene expression pattern between children with severe malaria and those with uncomplicated malaria through a dual RNA-seq approach. Peripheral blood samples were collected which contained substantial numbers of parasites that required no RNA enrichment prior to library preparation and sequencing.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Homo sapiens

SUBMITTER: Hyun Jae Lee

PROVIDER: E-MTAB-6413 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Modelling pathogen load dynamics to elucidate mechanistic determinants of host-Plasmodium falciparum interactions.

Georgiadou Athina A Lee Hyun Jae HJ Walther Michael M van Beek Anna E AE Fitriani Fadlila F Wouters Diana D Kuijpers Taco W TW Nwakanma Davis D D'Alessandro Umberto U Riley Eleanor M EM Otto Thomas D TD Ghani Azra A Levin Michael M Coin Lachlan J LJ Conway David J DJ Bretscher Michael T MT Cunnington Aubrey J AJ

Nature microbiology 20190617 9

During infection, increasing pathogen load stimulates both protective and harmful aspects of the host response. The dynamics of this interaction are hard to quantify in humans, but doing so could improve understanding of the mechanisms of disease and protection. We sought to model the contributions of the parasite multiplication rate and host response to observed parasite load in individual subjects infected with Plasmodium falciparum malaria, using only data obtained at the time of clinical pre ...[more]

PMID: 31209307

Publication: 1/2

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Project description:We aimed at finding differently expressed genes in whole blood cells of African children with asymptomatic Plasmodium falciparum infection (A), uncomplicated malaria (U), severe malarial anemia (A) and cerebral malaria (Ce) compared one to another and to healthy children (Co). Understanding malarial immunopathology in the human host represents and enormous challenge for transcriptomic research. In this work, we used microarray and real-time RT-PCR technology to pursue deeper knowledge about the mechanisms underlying this disease in African children. To this end, we investigated the genomic transcriptional profiles in whole blood of healthy children and children with asymptomatic infection, uncomplicated malaria, malaria associated with severe anemia and cerebral malaria and compared them with previously published microarray results. We were able to discriminate between the different presentations of P. falciparum infection using supervised and unsupervised clustering of microarray data and unsupervised double-hierarchical clustering of real-time RT-PCR results of a set of 22 genes known to be expressed in at least one of the principal blood cell lineages. We further found considerable overlap between genes regulated in Kenyan and Gabonese children with symptomatic malaria, in contrast to adults with acute malaria from Cameroon. Different signatures for transcription factor binding sites in promoters of genes either up-regulated in symptomatic disease, specifically up-regulated in uncomplicated malaria or specifically down-regulated in cerebral malaria point out that similar gene expression in each of these clinical presentations is probably a result of common regulation at the transcriptional level. Immunoglobulin production, complement regulation and IFN beta signalling emerged as most discrepant features between uncomplicated malaria and all other investigated presentations, correlating with IRF7 and ISRE binding signatures in the corresponding genes. Down-regulation of several genes in cerebral malaria seems instead to be a response to hypoxia orchestrated by AhRF, GABP and HIF1 transcription factors. ARG1, BPI, CD163, IFI27, HP and TNFAIP6 transcript levels correlated positively with lactatemia and inversely with hemoglobin concentration and should be evaluated as prognostic markers to direct early therapeutic measures and prevent malarial disease evolution and death.

Dataset Information

Dual RNA-seq of peripheral blood from Gambian children with severe or uncomplicated Plasmodium falciparum malaria

Publications

Modelling pathogen load dynamics to elucidate mechanistic determinants of host-Plasmodium falciparum interactions.

Similar Datasets

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