Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

EGAS00001001311_MalariaGEN_GWAS_summary_statistics_2015

ABSTRACT: Summary statistics for Malaria Genomic Epidemiology Network, "A novel locus of resistance to severe malaria in a region of ancient balancing selection", Nature (2015)

PROVIDER: EGAD00010001081 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Publications

A novel locus of resistance to severe malaria in a region of ancient balancing selection.

Band Gavin G Rockett Kirk A KA Spencer Chris C A CC Kwiatkowski Dominic P DP

Nature 20150930 7572

The high prevalence of sickle haemoglobin in Africa shows that malaria has been a major force for human evolutionary selection, but surprisingly few other polymorphisms have been proven to confer resistance to malaria in large epidemiological studies. To address this problem, we conducted a multi-centre genome-wide association study (GWAS) of life-threatening Plasmodium falciparum infection (severe malaria) in over 11,000 African children, with replication data in a further 14,000 individuals. H ...[more]

PMID: 26416757

Similar Datasets

Population Architecture using Genomics and Epidemiology, summary data (PAGE-summary)

Project description:Population Architecture using Genomics and Epidemiology, summary data (PAGE-summary)

| PRJNA168051 | ENA

Homo sapiens

Project description:Population Architecture using Genomics and Epidemiology, summary data (PAGE-summary)

| PRJNA168052 | ENA

Common asymptomatic and submicroscopic malaria infections in Western Thailand revealed in longitudinal molecular and serological studies: a challenge to malaria elimination.

Project description:Malaria is the most important vector-borne disease in Southeast Asia. In Thailand, malaria incidence has been in decline, with the annual parasite incidence dropping to 0.56 in 2007. The Myanmar-Thai border province of Tak is considered meso-endemic for malaria, and both Plasmodium vivax (Pv) and P. falciparum (Pf) are equally present. As part of the International Centers for Excellence in Malaria Research (ICEMR) - Southeast Asia project, malaria surveillance is conducted in Tak on both the healthy population and hospital patients, and parasite prevalence is reportedly <1%. However, little is known about the immuno-epidemiology associated with Pf and Pv infections in the region regarding the breadth and targets of the antibody response to the malaria parasites. Our hypothesis is that the serological profiles of the population will reflect the low parasite prevalence in Tak, showing little antibody reactivity to Pv and Pf. To examine this question, we developed a protein microarray displaying the top 500 most immunogenic antigens of these two Plasmodium species. We collected whole blood samples from healthy residents of Mae Salid Noi village during a Mass Blood Survey for malaria in the region. Whole blood was sent to UCI for qPCR and serology analysis. Blood plasma was probed on the protein microarray; genomic DNA was extracted from RBC pellets and screened by qPCR for infection confirmation and species identification. One-hundred percent (n=381) of serum samples were reactive to both Pv and Pf antigens, including all qPCR-negative samples.

2016-02-01 | GSE75593 | GEO

BMI EWAS summary stats

Project description:Summary statistics for a multi-cohort epigenome-wide association study. This includes summary statistics (effect-size, standard error, p-value) for 470,000 methylation markers.

| EGAD00010001029 | EGA

Early Genomic Amplifications in Blood-Stages of ARMD Plasmodium falciparum Acquiring De Novo Drug Resistance [Genome variation]

Project description:While many molecular changes associated with commonly used antimalarials are known, there remain important questions on how parasites arrive at the correct causal molecular solutions in a haploid genome. We selected for resistance to DSM1, a novel dihydroorotate dehydrogenase (DHODH) inhibitor with a non-biological triazolopyrimidine scaffold, in P. falciparum with the Accelerated Resistance to Multiple Drugs (ARMD) trait. While direct sequencing revealed no mutations in the target DHODH gene, comparative genomic hybridizations from four independently selected DSM1-resistant clones showed a large, single 34-95kb amplification in each clone. Each amplified region always included the DHODH locus. The length of this region and the resulting 2- to 3-fold DHODH copy number increase were verified at the RNA and protein level. DSM1 resistance was stable over several months of in vitro culture. Additional selection at higher DSM1 concentrations caused further gains in CNVs at the DHODH locus. The present system validated DHODH as a key target of the triazolopyrimidine antimalarial, DSM1 and, more importantly, captured large, random CNVs as an early step in the initiation of drug resistance in malaria parasites. This defined system is expected to be valuable for characterizing early, causal molecular steps leading to successful drug resistance gDNA from P. falciparum DSM1 resistant cell-line was hybridized against gDNA of parental strain, Dd2. DSM1 resistant cell culture was maintained under DSM1 at 333 nM, microarray data were obtained from three hybridizations using gDNA from three independent parasite cultures

2013-05-01 | E-GEOD-35732 | biostudies-arrayexpress

Early Genomic Amplifications in Blood-Stages of ARMD Plasmodium falciparum Acquiring De Novo Drug Resistance [Expression]

Project description:While many molecular changes associated with commonly used antimalarials are known, there remain important questions on how parasites arrive at the correct causal molecular solutions in a haploid genome. We selected for resistance to DSM1, a novel dihydroorotate dehydrogenase (DHODH) inhibitor with a non-biological triazolopyrimidine scaffold, in P. falciparum with the Accelerated Resistance to Multiple Drugs (ARMD) trait. While direct sequencing revealed no mutations in the target DHODH gene, comparative genomic hybridizations from four independently selected DSM1-resistant clones showed a large, single 34-95kb amplification in each clone. Each amplified region always included the DHODH locus. The length of this region and the resulting 2- to 3-fold DHODH copy number increase were verified at the RNA and protein level. DSM1 resistance was stable over several months of in vitro culture. Additional selection at higher DSM1 concentrations caused further gains in CNVs at the DHODH locus. The present system validated DHODH as a key target of the triazolopyrimidine antimalarial, DSM1 and, more importantly, captured large, random CNVs as an early step in the initiation of drug resistance in malaria parasites. This defined system is expected to be valuable for characterizing early, causal molecular steps leading to successful drug resistance RNA from P. falciparum DSM1 resistant cell-line was hybridized against RNA of parental strain, Dd2. DSM1 resistant cell culture was maintained under DSM1 at 333 nM, microarray data were obtained from three hybridizations using RNA from three independent parasite cultures

2013-05-01 | E-GEOD-35949 | biostudies-arrayexpress

The HER2-encoded miR-4728-3p regulates ESR1 through a non-canonical internal seed interaction

Project description:Since the early 1980s remarkable progress has been made in understanding the role of the HER2 locus in carcinogenesis, but many details of its regulatory network are still elusive. We recently reported the finding of 367 new human microRNA (miRNA) genes of which one, mir-4728, is encoded in an intron of the HER2 gene. Here, we confirm that the HER2 oncogene is a bi-functional locus encoding the membrane receptor and a functional miRNA gene. We further show that miR-4728-3p has alternative functionalities depending on the region used for interaction with its target; the canonical seed between nucleotides 2-8 or a novel, more internal seed shifted to nucleotides 6-12. Analysis of public data shows that this internal seed region, although rare compared to the far more abundant canonical 2-8 seed interaction, can also direct targeted down-regulation by other miRNAs. Through the internal seed, miR-4728-3p regulates expression of estrogen receptor alpha, an interaction that would have remained undetected if classic rules for miRNA-target interaction had been applied. In summary, we present here an alternative mode of miRNA regulation and demonstrate this dual function of the HER2 locus, linking the two major biomarkers in breast cancer. 6 samples treated with hsa-miR-4728-3p mimic and 6 samples treated with non-targeting control 4 samples treated with hsa-miR-1-3p mimic and 4 samples treated with non-targeting control

2014-08-13 | E-GEOD-55822 | biostudies-arrayexpress

A system for functional studies of the major virulence factor of malaria parasites [WGS]

Project description:PfEMP1 is a variable antigen displayed on red blood cells (RBCs) infected with the malaria parasite Plasmodium falciparum. PfEMP1 mediates binding of the infected cell to the endothelium of blood vessels, a major cause of severe manifestations of malaria. Each parasite encodes ∼60 different PfEMP1 variants of which only one is expressed at a time and switching between variants underlies immune evasion in the host and variant-specific severity of disease. PfEMP1 expression heterogeneity between parasites complicates its study and hampers genetic modification approaches as in many cells the modified locus is not expressed. Here we used selection linked integration to generate parasites all expressing the same PfEMP1 variant and permitting genomic modification of the expressed locus. Using this system, we study PfEMP1 trafficking, generate cell lines binding to all major endothelial receptors, survey the protein environment from functional PfEMP1 in the host cell and identify new proteins needed for PfEMP1 mediated sequestration. Overall, these approaches facilitate the study of the molecular and cellular biology of the key virulence factor of malaria parasites.

2024-09-01 | GSE275671 | GEO

Haemgen RBC GWAS - samples

Project description:Summary statistics from Haemgen RBC GWAS

| EGAD00010000300 | EGA

Identification of differences in CD4+ T-cell gene expression between people with asthma and healthy controls

Project description:Background: Functional enrichment analysis of genome-wide association study (GWAS)-summary statistics has suggested that immune cell-types, and especially CD4+ T-cells, play an important role in asthma pathogenesis. Despite this, CD4+ T-cells are under-represented in asthma transcriptome studies. Objective: To identify differences in gene expression between asthmatics and healthy controls in CD4+ T-cells. Methods: CD4+ T-cells were isolated within 2 hours from collection from peripheral blood from people with well-established asthma (n=33) and healthy controls (n=12). 3'-RNA-Seq was used to generate gene expression data. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify sets of co-expressed genes (modules). The asthma-associated modules were tested for enrichment of GWAS-identified asthma genes and gene ontology (GO) biological processes. For the genes in the asthma-associated modules, integration of eQTL and GWAS summary statistics (colocalisation), and protein-protein interaction (PPI) data was used to identify master regulators. Results: After quality control, 43 samples were available for the analysis. WGCNA identified three modules associated with asthma, which are strongly enriched for GWAS-identified asthma genes, antigen processing/presentation and immune response to viral infections. Colocalisation analysis of eQTL and GWAS summary statistics, together with PPI data, identified PTPRC as a master regulator of asthma gene-expression profiles in CD4+ T-cells. Conclusion: Unstimulated CD4+ T-cells from peripheral blood from asthmatics have different expression profiles, compared to healthy controls, for sets of genes involved in immune response to viral infections and antigen processing/presentation . Integration of genetic and protein-protein interaction data identified PTPRC as a master regulator of genes in asthma.

2023-12-27 | GSE217904 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data