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Specific methylation marks in promoter regions are associated to the pathogenic process of Chronic Chagas disease Cardiomyopathy by modifying transcription factor binding patterns [methylation]

ABSTRACT: Specific methylation marks in promoter regions are associated to the pathogenic process of Chronic Chagas disease Cardiomyopathy by modifying transcription factor binding patterns [methylation]

PROVIDER: PRJNA789590 | ENA |

REPOSITORIES: ENA

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Specific methylation marks in promoter regions are associated to the pathogenic process of Chronic Chagas disease Cardiomyopathy by modifying transcription factor binding patterns [methylation]

Project description:Chagas disease, caused by Trypanosoma cruzi, is an endemic parasitical disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including Chronic Chagasic Cardiomyopathy (CCC), which ranges from moderate to severe stages depending on the cardiac ejection fraction. The pathogenic process remains poorly understood, although genetic and epigenetic factors have already been proposed. Based on bulk RNA-seq and EPIC methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. We identified 4 main biological processes associated with the pathology development, including immune response, ion transport, cardiac muscle processes and nervous system. An in-depth study of the transcription factors binding sites in the differentially methylated regions corroborated the importance of these processes. We also conducted a methylation study on blood to identify potential biomarkers for CCC. Our data revealed 198 differentially methylated positions (DMPs) that could serve as biomarkers of the disease, of which 61 are associated with disease severity.

2022-07-18 | GSE191082 | GEO

Specific methylation marks in promoter regions are associated to the pathogenic process of Chronic Chagas disease Cardiomyopathy by modifying transcription factor binding patterns

Project description:Specific methylation marks in promoter regions are associated to the pathogenic process of Chronic Chagas disease Cardiomyopathy by modifying transcription factor binding patterns

| PRJNA789589 | ENA

Specific methylation marks in promoter regions are associated to the pathogenic process of Chronic Chagas disease Cardiomyopathy by modifying transcription factor binding patterns [RNA-Seq]

2022-07-18 | GSE191081 | GEO

Specific methylation marks in promoter regions are associated to the pathogenic process of Chronic Chagas disease Cardiomyopathy by modifying transcription factor binding patterns [RNA-Seq]

| PRJNA789591 | ENA

Blood DNA methylation marks discriminate Chagas cardiomyopathy disease clinical forms.

Project description:Chagas disease is a parasitic disease from South America, affecting around 7 million people worldwide. Decades after the infection, 30% of people develop chronic forms, including Chronic Chagas Cardiomyopathy (CCC), for which no treatment exists. Two stages characterized this form: the moderate form, characterized by a heart ejection fraction (EF) ≥ 0.4, and the severe form, associated to an EF < 0.4. We propose two sets of DNA methylation biomarkers which can predict in blood CCC occurrence, and CCC stage. This analysis, based on machine learning algorithms, makes predictions with more than 95% accuracy in a test cohort. Beyond their predictive capacity, these CpGs are located near genes involved in the immune response, the nervous system, ion transport or ATP synthesis, pathways known to be deregulated in CCCs. Among these genes, some are also differentially expressed in heart tissues. Interestingly, the CpGs of interest are tagged to genes mainly involved in nervous and ionic processes. Given the close link between methylation and gene expression, these lists of CpGs promise to be not only good biomarkers, but also good indicators of key elements in the development of this pathology.

| S-EPMC9558220 | biostudies-literature

Specific methylation marks in promoter regions are associated to the pathogenic process of Chronic Chagas disease Cardiomyopathy by modifying transcription factor binding patterns

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-07-18 | GSE191083 | GEO

Immunologic changes are detectable in the peripheral blood transcriptome of clinically asymptomatic Chagas cardiomyopathy patients

Project description:Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected parasitic disease that affects approximately 6 million individuals worldwide. Of those infected, 20-30% will go on to develop chronic Chagas cardiomyopathy (CCC), and ultimately many of these individuals will progress to advanced heart failure. The mechanism by which this progression occurs is poorly understood, as few studies have focused on early CCC. In this study, we sought to understand the physiologic changes associated with T. cruzi infection and the development of CCC. We analyzed gene expression in the peripheral blood of asymptomatic Chagas patients with early structural heart disease, Chagas patients without any signs or symptoms of disease, and Chagas-negative patients with and without early structural heart disease. Our analysis shows that early CCC was associated with a downregulation of various peripheral immune response genes, with gene expression changes suggestive of reduced antigen presentation and T cell activation. Notably, these genes and processes were distinct from those of early cardiomyopathy in Chagas-negative patients, suggesting that the processes mediating CCC may be unique from those mediating progression to other cardiomyopathies. This work highlights the importance of the immune response in early CCC, providing insight into the early pathogenesis of this disease. The changes we have identified may serve as biomarkers of progression and could inform strategies for the treatment of CCC in its early stages, before significant cardiac damage has occurred.

2024-10-04 | GSE244827 | GEO

Comparison of Trypanosoma cruzi strains from patients with indeterminate and cardiac forms of Chagas disease

Project description:Gene expression profiles in T. cruzi strains isolated from individuals presenting the indeterminate and cardiac forms of Chagas disease. Genetic markers differentially expressed may be of potential use in diagnostic/prognostic tests and could assist the understanding of pathogenesis of Chagas disease Keywords: other

2005-10-08 | GSE1828 | GEO

Crosstalk between gene body DNA methylation, H3K9me3 and H3K36me3 chromatin marks and transcription

Project description:This SuperSeries is composed of the following subset Series: GSE26018: Crosstalk between gene body DNA methylation, H3K9me3 and H3K36me3 chromatin marks and transcription [HuEx-1_0-st] GSE26019: Crosstalk between gene body DNA methylation, H3K9me3 and H3K36me3 chromatin marks and transcription [HuGene-1_0-st] GSE26038: Crosstalk between gene body DNA methylation, H3K9me3 and H3K36me3 chromatin marks and transcription [HuEx-1_0-st, transcript] GSE26040: Relationship between gene body DNA methylation and intragenic H3K9me3 and H3K36me3 chromatin marks Refer to individual Series

2011-03-31 | E-GEOD-26020 | biostudies-arrayexpress

Self and parasite-derived peptides selected upon DERAA-bearing HLA-DRB1 alleles activate CD4+ T cells from Chagas cardiomyopathy patients and are associated with ventricular dysfunction

Project description:Human infection with the protozoan Trypanosoma cruzi causes Chagas disease, which may lead to a deadly dilated cardiomyopathy resulting from T-cell-mediated inflammation. We found that specific HLA-DRB1 alleles (*0103, *0402, *1301, and *1302) that display the DERAA motif are linked to this severe clinical manifestation of Chagas disease. We employed computational analysis, in vitro functional assays, and single-cell RNA sequencing to determine the response of CD4+ T cells from indeterminate (IND) and cardiac (CCC) Chagas patients to peptides selected on DERAA-bearing alleles. We observed that these alleles display binding affinity towards host-derived peptides with sequence similarity to parasite-derived proteins. These peptides can activate and induce proliferation of CD4+ T-cells from CCC, but not IND. Importantly, the magnitude of this response correlated with the severity of ventricular dysfunction and increased production of soluble factors associated with myocardial fibrosis. Analysis of differentially expressed genes (DEGs) in activated CD4+ T-cells from individuals with the DERAA-DRB1 alleles demonstrated a high expression of cytotoxic, chemotactic and proapoptotic genes, linking these cells with pathogenic functions. Finally, we observed the upregulation of genes that code for the host proteins that contain the potentially pathogenic peptides in the cardiac tissue of CCC, suggesting their involvement in cardiomyopathy. Our findings highlight the ability of CD4+ T-cells from CCC patients to recognize and react to foreign and self-peptides, thereby emphasizing the importance of HLA-DRB1 alleles in the presentation of potentially pathogenic antigens and in the amplification of CCC pathology.

2025-05-29 | GSE295194 | GEO

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