Study Info
INDA Accessions: INRP000433
INSDC Accessions: PRJEB108952, ERP189790
- Title: Investigating the epigenetic landscape of severe malaria: a genome-wide methylation analysis of Plasmodium vivax clinical isolates
- Data Type : Whole Genome Sequencing
- Descriptive Title: DNA Methylation in Plasmodium vivax
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Organism:
Scientific Name(Taxon Id): Plasmodium vivax Sal-1 (126793) Common Name:
Other Info
- Abstract: Background Globally, malaria remains one of the most widespread infectious diseases. According to the World Malaria Report 2023, half of the worlds population is at risk of malaria caused by Plasmodium vivax. The parasites complex life cycle requires tight regulation of gene expression, which is controlled at both transcriptional and posttranscriptional levels. Further, as a survival strategy, in response to the variable conditions encountered in host environments, DNA base modifications may play a pivotal role in regulating gene expression during the different parasite stages. Epigenetic modulation links to almost every critical biological process and may impact mechanisms of parasites drug resistance. Materials and Methods This study employs Oxford Nanopore DNA Sequencing to identify the epigenetic signatures ie 5-Methylcytosine-5mC, 5-hydroxymethylcytosine-5hmC by using computational tools. To gain more insights into these methylation signatures, we also investigated the differential methylation regions DMRs in promoter, gene body and enhancer at a single nucleotide level resolution in clinical samples of P vivax showing both uncomplicated and complicated manifestation. Additionally, gene set enrichment analysis was performed on regions significantly enriched for DMRs, and these findings were correlated with microarray expression datasets from same samples which have been experimentally validated in our lab. Result We generated the first genome-wide DNA methylation maps 5mC and 5hmC at single CpG resolution in clinical isolates of Plasmodium vivax between uncomplicated and complicated cases, covering all three asexual parasite stages. Our findings reveal that the epigenetic landscape is significantly altered in severe disease states, with most changes occurring in regulatory regions such as promoters and enhancers. Notably, we identified differentially methylated regions DMRs in severe malaria cases and compared these with transcriptome expression profiles, highlighting dysregulation in key pathways related to immune evasion, pathogenesis, and drug resistance. Additionally, gene ontology analysis of these genes revealed enrichment in various biological pathways, including the regulation of gene expression, DNA-templated transcription, RNA biosynthesis, and cellular metabolic processes. Taken together, our findings establish a clear link between DNA methylation alterations and gene expression dysregulation. This suggests that such epigenetic changes may facilitate parasite survival under the hostile environmental conditions of severe disease. Conclusions Substantial genomic alternations in DNA methylation are observed in clinical samples with different disease states from malaria. Changes in gene expression correlates to differential methylation, suggesting a functional role for DNA methylation in transcriptional regulation during severe disease states. Strikingly, the differential methylation status of certain key genes has shown significant epigenetic changes involved in immune evasion and pathogenesis processes. DMRs containing drug resistance marker genes may affect efficacy of drug treatment of parasites. Multiple genes and pathways that are dysregulated have been identified and offer future potential targets for biomarker development, novel therapies, and potent leads for future studies.
- Linked publications:
- Center Name: Priyanka Roy, Arnav Bharti, Ashis Das, Birla Institute of Technology and Science (BITS), Pilani Campus
- Number of Base(Total) Mbp: 26,086,009,883
- Size in bytes(Total): 125,699,032,048
- Number of sample:
- Number of Runs:
- Number of Sequences:
- Number of Assembly:
- Number of Variant files:
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