Ontology highlight
ABSTRACT:
PROVIDER: PRJNA683732 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13222200_1.fastq.gz | Fastqsanger.gz | |||
| SRR13222200_2.fastq.gz | Fastqsanger.gz | |||
| SRR13222300_1.fastq.gz | Fastqsanger.gz | |||
| SRR13222300_2.fastq.gz | Fastqsanger.gz | |||
| SRR13222201_1.fastq.gz | Fastqsanger.gz |
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Project description:Further understanding of the molecular mediators of alternative RBC invasion phenotypes in endemic malaria parasites will support malaria blood stage vaccine or drug development. This study investigated the prevalence of SA-dependent and SA-independent RBC invasion pathways in endemic P. falciparum parasites from Cameroon and compared the schizont stage transcriptomes in these two groups with the goal of uncovering the wider repertoire of transcriptional variation associated with the use of alternative RBC invasion pathway phenotypes. Two-colour flow cytometry-based invasion-inhibition assay against RBCs treated with neuraminidase, trypsin and chymotrypsin and deep RNA sequencing of schizont stages harvested in the first ex-vivo replication cycle in culture were employed in this investigation. RBC invasion phenotypes were determined for 63 isolates from asymptomatic children with uncomplicated malaria. Approximately 80% of the isolates invaded neuraminidase-treated but not chymotrypsin-treated RBCs, representing sialic acid (SA)-independent pathways of RBC invasion. The schizont transcriptome profiles of 16 isolates with invasion phenotypes revealed a total of 5136 gene transcripts, with 85% of isolates predicted at schizont stages. Two distinct transcriptome profile clusters belonging to SA-dependent and SA-independent parasites were obtained by data reduction with principal component analysis. Differential analysis of gene expression between the two clusters implicated in addition to the well characterized adhesins, the up-regulation of genes encoding proteins mediating merozoite organelle discharges and several conserved, virulent, merozoite associated and exported proteins. The latter majority of which have been shown to have structural and physiological relevance to RBC surface remodelling and immune evasion in malaria and thus, have potential as anti-invasion targets.
2025-01-22 | GSE264687 | GEO
Project description:Malaria infection drives tolerogenic cell responses which protects from high inflammation and immunopathogenesis but reduces parasite control and adaptive immunity. Here, we comprehensively map responses across innate and adaptive cells. The results of this Controlled Human Malaria Infection study are presented in three independent publications. Blood samples from 4 donors were collected prior to infection (day 0), at peak infection (day 8) and 14 or 15 and 27-36 days (end of study, EOS) after inoculation (in analyses these time points are grouped as 0, 8, 14/15 and EOS). Participants were healthy malaria naïve adults with no prior exposure to malaria or residence in malaria-endemic regions. For trials NCT02867059, NCT02783833, NCT02431637 all participants received the same study drug (no-randomization) and 3D7-strain parasites. For NCT02431650, participants were randomized 1:1 to receive study drug or control and 3D7-strain parasites. Samples used here were from samples opportunistically collected from volunteers who consented to donate blood for immunological studies within the parent clinical trial. As such, no sample size estimation was performed for this immunology study.
2025-10-05 | GSE253661 | GEO
Project description:Plasmodium falciparum (Pf) malaria causes high rates of morbidity and mortality and lacks an effective vaccine. Clinical immunity develops in residents of malaria endemic regions which confers reduced clinical symptoms during infection and protects against severe disease. We hypothesized that understanding the immune mechanisms of clinical immunity could inform vaccine design to improve efficacy. We compared the peripheral blood cellular and humoral immune responses during Pf malaria infection between clinically susceptible and protected participants from a malaria endemic region in Malawi during a prospective 18-month longitudinal study. Participant classifications were defined by the number of recurrent clinical malaria episodes with susceptible participants having more than three while protected less than one episode during the study period. Protected participants exhibited higher immunoglobulin G (IgG) breadth and titers against Pf antigens, and greater antibody (Ab)-dependent Pf opsonization compared to susceptible participants, consistent with our classifications. Using high dimensional mass cytometry (CyTOF) and spectral flow cytometry, and single-cell transcriptomic analyses, we identified expanded memory CD4+ T cell clonotypes in the blood of protected participants undergoing malaria infection. These cells express a strong cytolytic T helper 1 effector program with transcripts encoding granzymes (A, B, H, M), granulysin, NKG7 and the ZEB2 master transcriptional regulator of terminally differentiated effector T cells. ZEB2+ memory CD4+ T cells were CD39hiTIGIThi and expressed multiple chemotactic and inhibitory receptors. Yet, their levels of several chemokine and checkpoint inhibitory receptors were reduced in protected compared to susceptible individuals. We propose that clonally expanded ZEB2+ cytolytic memory CD4+ Th1 cells could represent essential contributors to clinical immunity against Pf malaria infection.
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2018-09-28 | E-MTAB-6448 | 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:Background: Plasmodium falciparum causes the majority of malaria mortality worldwide, and the disease occurs during the asexual red blood cell (RBC) stage of infection. In the absence of an effective and available vaccine, and with increasing drug resistance, asexual RBC stage parasites are an important research focus. In recent years, mass spectrometry-based proteomics using Data Dependent Acquisition (DDA) has been extensively used to understand the biochemical processes within the parasite. However, DDA is problematic for the detection of low abundance proteins, protein coverage, and has poor run-to-run reproducibility. Results: Here, we present a comprehensive P. falciparum-infected RBC (iRBC) spectral library to measure the abundance of 44,449 peptides from 3,113 P. falciparum and 1,617 RBC proteins using a Data Independent Acquisition (DIA) approach. The spectral library includes proteins expressed in the three morphologically distinct RBC stages (ring, trophozoite, schizont), the RBC compartment of trophozoite-iRBCs, and the cytosolic fractions from uninfected RBCs (uRBC). This spectral library contains 87% of P. falciparum proteins with previously blood-stage protein-level evidence as well as 692 previously unidentified proteins. The P. falciparum spectral library was successfully applied to generate semi-quantitative proteomics datasets that characterise the three distinct asexual parasite stages in RBCs, and compare artemisinin resistant (Cam3.IIR539T) and sensitive (Cam3.IIrev) parasites. Conclusion: A reproducible, high-coverage proteomics spectral library and analysis method has been generated for investigating sets of proteins expressed in the iRBC stage of P. falciparum malaria. This will provide a foundation for an improved understanding of parasite biology, pathogenesis, drug mechanisms and vaccine candidate discovery for malaria.
2021-11-15 | PXD027301 | Pride
Project description:Background: Plasmodium falciparum causes the majority of malaria mortality worldwide, and the disease occurs during the asexual red blood cell (RBC) stage of infection. In the absence of an effective and available vaccine, and with increasing drug resistance, asexual RBC stage parasites are an important research focus. In recent years, mass spectrometry-based proteomics using Data Dependent Acquisition (DDA) has been extensively used to understand the biochemical processes within the parasite. However, DDA is problematic for the detection of low abundance proteins, protein coverage, and has poor run-to-run reproducibility. Results: Here, we present a comprehensive P. falciparum-infected RBC (iRBC) spectral library to measure the abundance of 44,449 peptides from 3,113 P. falciparum and 1,617 RBC proteins using a Data Independent Acquisition (DIA) approach. The spectral library includes proteins expressed in the three morphologically distinct RBC stages (ring, trophozoite, schizont), the RBC compartment of trophozoite-iRBCs, and the cytosolic fractions from uninfected RBCs (uRBC). This spectral library contains 87% of P. falciparum proteins with previously blood-stage protein-level evidence as well as 692 previously unidentified proteins. The P. falciparum spectral library was successfully applied to generate semi-quantitative proteomics datasets that characterise the three distinct asexual parasite stages in RBCs, and compare artemisinin resistant (Cam3.IIR539T) and sensitive (Cam3.IIrev) parasites. Conclusion: A reproducible, high-coverage proteomics spectral library and analysis method has been generated for investigating sets of proteins expressed in the iRBC stage of P. falciparum malaria. This will provide a foundation for an improved understanding of parasite biology, pathogenesis, drug mechanisms and vaccine candidate discovery for malaria.
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2019-08-22 | PXD013852 | Pride