The genomic architecture of host whole blood transcriptional response to malaria infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE34404 | GEO | 2012/09/04
SECONDARY ACCESSION(S): PRJNA149639
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of the effect of malaria infection on whole blood gene expression and uncovering regulatory effects using eQTL analysis. Testing for relashionships between genotype, expression and malaria phenotypes. We generated whole blood gene expression profiles and genotypes from 155 West-African children including 94 cases undergoing the symptomatic phase of blood-stage Plasmodium falciparum infection and 61 age-matched controls. PCA, analysis of covariance and eQTL analysis were performed on the data.
2012-09-04 | E-GEOD-34404 | biostudies-arrayexpress
Project description:Few genotype-phenotype associations identified by genome-wide association studies (GWAS) have been defined mechanistically, precluding thorough assessment of their impact on human health. We conducted an expression quantitative trait loci (eQTL) mapping analysis in human erythroblasts and found erythroid-specific eQTLs for ATP2B4, the main calcium ATPase of red blood cells (RBC). The same SNPs were previously associated with mean corpuscular hemoglobin concentration (MCHC) and susceptibility to severe malaria infection. We showed that Atp2b4-/- mice demonstrate increased MCHC, confirming ATP2B4 as the causal gene at this GWAS locus. Using CRISPR-Cas9, we fine-mapped the genetic signal to an erythroid-specific enhancer bound by GATA1 and TAL1. These results illustrate the importance to combine transcriptome, epigenome, and genome editing approaches in phenotype-relevant cells to characterize non-coding regulatory elements associated with human complex diseases and traits. Our studies suggest ATP2B4 as a potential target to modulate RBC hydration in erythroid disorders and malaria infection.
2017-07-17 | GSE98992 | GEO
Project description:Few genotype-phenotype associations identified by genome-wide association studies (GWAS) have been defined mechanistically, precluding thorough assessment of their impact on human health. We conducted an expression quantitative trait loci (eQTL) mapping analysis in human erythroblasts and found erythroid-specific eQTLs for ATP2B4, the main calcium ATPase of red blood cells (RBC). The same SNPs were previously associated with mean corpuscular hemoglobin concentration (MCHC) and susceptibility to severe malaria infection. We showed that Atp2b4-/- mice demonstrate increased MCHC, confirming ATP2B4 as the causal gene at this GWAS locus. Using CRISPR-Cas9, we fine-mapped the genetic signal to an erythroid-specific enhancer bound by GATA1 and TAL1. These results illustrate the importance to combine transcriptome, epigenome, and genome editing approaches in phenotype-relevant cells to characterize non-coding regulatory elements associated with human complex diseases and traits. Our studies suggest ATP2B4 as a potential target to modulate RBC hydration in erythroid disorders and malaria infection.
2017-06-23 | GSE90878 | GEO
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.
2019-01-23 | GSE1124 | GEO
Project description:Here, we integrated genome-wide genotype, gene expression and phenotype (viremia level (VL) and weight gain (WG)) data to identify genetic variations and genes that are associated with variation in pigs’ response to PRRSV infection. RNA-seq analysis of peripheral blood samples collected just prior to experimental challenge (day 0) and at 4, 7, 10 and 14 days post infection from 44 pigs revealed 6430 differentially expressed genes after infection. We mapped genetic variations that are associated with inter-individual differences in expression at each day and found evidence of cis expression quantitative trait loci (cis-eQTL) for 1201 genes. Associations between cis-eQTL markers and phenotypes using 383 pigs indicated that host genotype-dependent reduced expression of GBP5, CD1D, PAK1, and USP18 contribute to higher VL or lower WG in response to PRRSV infection. We also validated that cis-eQTLs of these candidate genes for host response to PRRSV infection generally acted by a mechanism involving allele-specific expression.
2017-03-31 | GSE78762 | GEO
Project description:Host gene and protein expression impact susceptibility to clinical malaria, but the balance of immune cell populations, cytokines and genes that contributes to protection, remains incompletely understood. To identify determinants of host susceptibility to clinical malaria at a time when acquired immunity is developing, we analyzed peripheral blood mononuclear cells (PBMCs) collected from children who differed in susceptibility to clinical malaria, all from a small town in Mali. PBMCs were collected from children aged 4-6 years at the start, peak and end of the malaria season. We characterized the immune cell composition and cytokine secretion for a subset of 20 children per timepoint (10 children with no symptomatic malaria age-matched to 10 children with >2 symptomatic malarial illnesses), and gene expression patterns for six children (three per cohort) per timepoint. We noted higher frequency of HLA-DR+ CD4 T cells in protected children during the peak of the malaria season and comparable levels cytokine secretion after stimulation with malaria schizonts across all three time points. We also observed differences between the two groups of children in the expression of genes related to cell death and inflammation; in particular, inflammatory genes such as CXCL10 and STAT1 and apoptotic genes such as XAF1 were upregulated in susceptible children before the transmission season began. This suggests that differences in apoptotic and inflammatory gene expression patterns can predict susceptibility to clinical malaria.
2023-06-29 | GSE234970 | GEO
Project description:Whole blood transcriptomes from a longitudinal study of 5 Malawian children who first present with severe Plasmodium falciparum malaria, and return in one month with mild malaria We used microarrays to identify transcripts that were associated with each clinical presentation. A blood sample was taken upon presentation during the severe and mild malaria episodes in 5 Malawian children (total n=5 pairs) followed by RNA extraction and hybridization on Affymetrix GeneChip Human Gene 1.0 ST Array, using a paired analysis
2012-01-11 | E-GEOD-33811 | biostudies-arrayexpress
Project description:Whole blood transcriptomes from a longitudinal study of 5 Malawian children who first present with severe Plasmodium falciparum malaria, and return in one month with mild malaria We used microarrays to identify transcripts that were associated with each clinical presentation.
2012-01-11 | GSE33811 | GEO
Project description:Subjects are children from Kilifi District Hospital, Kenya, recruited in 2001 malaria season. total RNA extracted from PaxGene tubes, total RNA and Stratagene Universal reference RNA underwent linear amplification (Message Amp, Ambion). Amplified RNA directly labelled Cy5 and Cy3 and hybridised to 'lymphochip' arrays (print run - lc36n). Scanned on Axon 4000B scanner using GenePix 4.0 software. Clinical sample ID provided in 'Disease State Description' corresponds with Sample ID in Table 1 "Clinical Information for the micro-array samples" in the associated publication. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Keywords: disease_state_design
2005-07-09 | GSE2900 | GEO
Project description:We performed a genome-wide profiling of miRNAs and mRNA, DNA sequencing of human whole blood sample to identify miRNAs responsive to P.falciparum (P.f) infection and/or associated with parasite load. We identified a set of 72 miRNAs that are positively or negatively associated with parasitemia. We also performed expression quantitative trait loci of miRNAs(miR-eQTL) of P.f infected individuals. The miR-eQTL dataset allowed us to determine relevant genetic variant responsible for miRNAs expression differences between P.f infected individuals and find novel malaria-associated miRNAs
2020-09-05 | GSE144413 | GEO