Similar Datasets
Project description:We performed Agilent chip analysis with synchronized 0-6h ring stage parasites of three P.falciparum lines within their third life cycle, to study the change of expression profiling when knocking down PfSWIB .
2020-02-18 | GSE141404 | GEO
Project description:We performed RNA-Seq analysis with synchronized 0-6h ring stage parasites of three P.falciparum lines within their third life cycle, to study the change of expression profiling when knocking down PfSWIB. The comparison analysis on screening of differentially expressed genes was done in parasite lines including 3D7(wild type: blank control), PfSWIB (wild type: self-control) and PfSWIB∆ (PfSWIB knockdown). Approximately 10.8% of the transcripts showed up-regulation between the PfSWIB-KD and two WT parasite, whereas 11.9% showed down-regulation (Fold change>1.5, P<0.05). Hierarchical clustering of differentially expressed genes uncovered several transcription factors such as PfApiAP2 family and PfSir2B, as well as certain histone modification enzymes, which proved to be involved in regulating on var gene transcription. We further screened out a number of var genes which exhibited differential expression among different lines, and performed qPCR on 44 differentially expressed vars in the PfSWIB vs PfSWIB∆ comparison group based on the RNA-seq results, to study the transcription patterns of upsA-, upsB- and upsC-subtype var genes. We found that most upsA- and upsC- type vars were significant down-regulated in PfSWIB∆ line. In contrast, the expression pattern of partial upsB vars presented a distinct change in PfSWIB∆ line. The RNA-seq and qPCR analysis provide a better understanding of the mechanism and function of PfSWIB on regulating the expression switching and clonal variation of var gene family contributing to the pathogenesis in malaria parasites.
2020-02-18 | GSE141155 | GEO
Project description:Screening of differentially expressed genes in three Plasmodium falciparum parasite lines
| PRJNA595386 | ENA
Project description:Screening of differentially expressed genes in three Plasmodium falciparum parasite lines [expression]
| PRJNA593289 | ENA
Project description:Screening of differentially expressed genes in three Plasmodium falciparum parasite lines [RNA-seq]
| PRJNA592366 | ENA
Project description:The emergence and spread in Southeast Asia of Plasmodium falciparum resistance to artemisinin (ART) derivatives, the cornerstone of first-line artemisinin-based combination therapies (ACTs), underscore the urgent need to identify suitable replacement drugs. Discovery and development efforts have identified a series of ozonides with attractive chemical and pharmacological properties that are being touted as suitable replacements. Partial resistance to ART, defined as delayed parasite clearance in malaria patients treated with an ART derivative or an ACT, has been associated with mutations in the P. falciparum K13 gene. In light of reports showing that ART derivatives and ozonides share similar modes of action, we have investigated whether parasites expressing mutant K13 are cross-resistant to the ozonides OZ439 (artefenomel) and OZ227 (arterolane). This work used a panel of culture-adapted clinical isolates from Cambodia that were genetically edited to express variant forms of K13. Phenotypic analyses employed ring-stage survival assays (ring-stage survival assay from 0 to 3 h [RSA0-3h]), whose results have earlier been shown to correlate with parasite clearance rates in patients. Our results document cross-resistance between OZ277 and dihydroartemisinin (DHA), a semisynthetic derivative of ART, in parasites carrying the K13 mutations C580Y, R539T, and I543T. For OZ439, we observed cross-resistance only for parasites that carried the rare K13 I543T mutation, with no evidence of cross-resistance afforded by the prevalent C580Y mutation. Mixed-culture competition experiments with isogenic lines carrying modified K13 revealed variable growth deficits depending on the K13 mutation and parasite strain and provide a rationale for the broad dissemination of the fitness-neutral K13 C580Y mutation throughout strains currently circulating in Southeast Asia.IMPORTANCE ACTs have helped halve the malaria disease burden in recent years; however, emerging resistance to ART derivatives threatens to reverse this substantial progress. Resistance is driven primarily by mutations in the P. falciparum K13 gene. These mutations pose a threat to ozonides, touted as promising alternatives to ARTs that share a similar mode of action. We report that DHA was considerably more potent than OZ439 and OZ277 against ART-sensitive asexual blood-stage parasites cultured in vitro We also document that mutant K13 significantly compromised the activity of the registered drug OZ277. In contrast, OZ439 remained effective against most parasite lines expressing mutant K13, with the exception of I543T that merits further monitoring in field-based OZ439 efficacy studies. K13 mutations differed considerably in their impact on parasite growth rates, in a strain-dependent context, with the most prevalent C580Y mutation being fitness neutral in recently culture-adapted strains from Cambodia, the epicenter of emerging ART resistance.
| S-EPMC5388803 | biostudies-literature
Project description:To investigate, by RNA-Sequencing (RNA-seq), the expression profile of two P. falciparum strains (control 3D7; protein kinase 7 knock-out strain, Pfpk7- and PfpK7 complement) to the presence of melatonin.
2016-10-01 | E-MTAB-3667 | biostudies-arrayexpress
Project description:The antigenic variation and cytoadherence of Plasmodium falciparum-infected erythrocytes are modulated by a family of variant surface proteins encoded by the var multigene family. The var genes occur on multiple chromosomes, often in clusters, and 50 to 150 genes are estimated to be present in the haploid parasite genome. Transcripts from var genes have been previously mapped to internal chromosome positions, but the generality of such assignments and the expression sites and mechanisms that control switches of var gene expression are still in early stages of investigation. Here we describe investigations of closely related var genes that occur in association with repetitive elements near the telomeres of P. falciparum chromosomes. DNA sequence analysis of one of these genes (FCR3-varT11-1) shows the characteristic two-exon structure encoding expected var features, including three variable Duffy binding-like (DBL) domains, a transmembrane sequence, and a carboxy-terminal segment thought to anchor the protein product in knobs at the surface of the parasitized erythrocyte. FCR3-varT11-1 cross-hybridizes with var genes located close to the telomeres of many other P. falciparum chromosomes, including a transcribed gene (FCR3-varT3-1) in chromosome 3 of the P. falciparum FCR3 line. The relatively high level transcription from this gene shows that the polymorphic chromosome ends of P. falciparum, which have been proposed to be transcriptionally silent, can be active expression sites for var genes. The pattern of the FCR3-varT11-1 and FCR3-varT3-1 genes are variable between different P. falciparum lines, presumably due to DNA rearrangements. Thus, recombination events in subtelomeric DNA may have a role in the expression of novel var forms.
| S-EPMC231785 | biostudies-other
Project description:BackgroundPolymyositis (PM), a prevalent inflammatory myopathy, currently lacks defined pathogenic mechanism. To illuminate its pathogenesis, we integrated bioinformatics and clinical specimens to examine potential aberrant gene expression patterns and their localization.MethodsWe obtained GSE128470 and GSE3112 dataset from the Gene Expression Omnibus, performed Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis using CiberSort, identified differentially expressed genes with Limma, conducted functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, constructed a Protein-Protein Interaction network, and identified hub genes using Cytoscape. ROC analysis evaluated hub gene diagnostic accuracy for PM, validated their expression levels with clinical specimens.ResultsDEG analysis revealed 51 upregulated and 779 downregulated genes. Gene Ontology (GO) analysis implicated Type I interferon (IFN-Ⅰ) signaling, while KEGG pointed to cell adhesion molecule activation and oxidative phosphorylation inhibition. Protein-Protein Interaction (PPI) analysis identified 8 diagnosffftic hub genes. Clinical samples confirmed their upregulation in PM, especially IRF1 and IRF9 between muscle fibers. Different immune cell infiltrations were observed in PM patients versus controls.ConclusionsOur study explores potential pathogenic factors, diagnostic markers, and immune cells in PM, with a focus on verifying IRF1 and IRF9 upregulation in the IFN-I signaling pathway. These findings bear significance for PM diagnosis and treatment.
| S-EPMC10839795 | biostudies-literature
Project description:Background: We aimed to make an integrated analysis of published transcriptome and DNA methylation dataset to ascertain the key differentially methylated and differentially expressed genes for Alzherimer's disease (AD). Methods: Two gene expression microarrays and 1 gene methylation microarray were downloaded for identification of differentially expressed genes and differentially methylated genes. Then, we used various biological information databases to annotate the functions of the differentially-methylated/expressed genes, and screen out key genes and important signaling pathways. Finally, we validate the differentially-methylated/expressed genes in the additional online datasets and in blood from AD patients.Results: A total of 8 hub hypomethylated-high expression genes were obtained, including Rac family small GTPase 2, FGR proto-oncogene, Src family tyrosine kinase, LYN proto-oncogene, Src family tyrosine kinase, protein kinase C delta, myosin IF, integrin subunit alpha 5, semaphorin 4D, and growth arrest specific protein 7. Some enriched signaling pathways of hypomethylated-high expression genes were identified, including regulation of actin cytoskeleton, chemokine signaling pathway, Fc gamma R-mediated phagocytosis, and axon guidance. Conclusion: Differentially-methylated/expressed genes are likely to be associated with AD.
| S-EPMC10624077 | biostudies-literature