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Direct sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution unravels their distinct roles in Alzheimer’s disease [RNA-Seq]

ABSTRACT: Direct sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution unravels their distinct roles in Alzheimer’s disease [RNA-Seq]

PROVIDER: PRJNA1231059 | ENA |

REPOSITORIES: ENA

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Direct sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution unravels their distinct roles in Alzheimer’s disease [BS-Seq]

Project description:Direct sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution unravels their distinct roles in Alzheimer’s disease [BS-Seq]

| PRJNA1231066 | ENA

Direct sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution unravels their distinct roles in Alzheimer’s disease [BS-Seq mESC]

Project description:Direct sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution unravels their distinct roles in Alzheimer’s disease [BS-Seq mESC]

| PRJNA1231068 | ENA

Direct sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution unravels their distinct roles in Alzheimer’s disease [RNA-Seq]

Project description:5-hydroxymethylcytosine (5hmC) constitutes up to 20% of 5-methylcytosine (5mC) in mammalian cells. As conventional bisulfite sequencing is unable to distinguish 5hmC from 5mC, several methods have been proposed to detect 5hmC and infer 5mC levels by subtracting 5hmC from whole-genome bisulfite sequencing data. This subtraction approach, however, can lead to the underestimation of 5mC levels at sites with high 5hmC abundance. Here, we present two orthogonal methods: CMD1-Deaminase sequencing and CMD1-TET bisulfite sequencing, which enable the direct and independent detection of 5mC. In combination with ACE-seq or TAB-seq, these techniques facilitate an accurate distinction between 5mC and 5hmC, eliminating the need for subtraction. Using these approaches, we generated a comprehensive landscape of 5mC and 5hmC in the hippocampus of the Alzheimer's disease (AD) model mice. Notably, while 5hmC levels were substantially reduced in the AD mice, 5mC levels remained largely unchanged, suggesting a critical role for 5hmC as an independent epigenetic mark in the pathogenesis of AD.

2025-07-17 | GSE290949 | GEO

Direct sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution unravels their distinct roles in Alzheimer’s disease [BS-Seq]

2025-07-17 | GSE290950 | GEO

Direct sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single-base resolution unravels their distinct roles in Alzheimer’s disease [BS-Seq mESC]

2025-07-17 | GSE290951 | GEO

Differential 5-methylcytosine and 5-hydroxymethylcytosine in Parkinson’s and Alzheimer’s Disease.

Project description:Differential 5-methylcytosine and 5-hydroxymethylcytosine in Parkinson’s and Alzheimer’s Disease.

| PRJNA576484 | ENA

Bisulfite-free direct detection of 5-methylcytosine and 5-hydroxymethylcytosine at base resolution

Project description:Bisulfite-free direct detection of 5-methylcytosine and 5-hydroxymethylcytosine at base resolution

| PRJNA448064 | ENA

Differential 5-methylcytosine and 5-hydroxymethylcytosine in Parkinson’s and Alzheimer’s Disease.

Project description:Background: 5-methylcytosine (5-mC) and its oxidized form, 5-hydroxymethylcytosine (5-hmC), are distinct epigenetic marks that help regulate gene expression in the mammalian brain. Existing studies have identified associations between 5-mC and neurodegenerative disease, but little work has examined the potential role of 5-hmC in Parkinson’s disease (PD) or Alzheimer’s disease (AD). Here, we utilized PD postmortem brain tissue and a public dataset from postmortem AD brains to analyze the effect of neurodegenerative disease on paired 5-mC and 5-hmC levels. Results: In PD samples, we measured genome-wide 5-mC and 5-hmC from control (n=3) and PD (n=6) brains using the Illumina EPIC array combined with bisulfite and oxidative bisulfite treatments (BS/oxBS-EPIC). In publicly sourced data, genome-wide 5-mC and 5-hmC were measured from control (n=25) and AD (n=62) human entorhinal cortex tissue using the Illumina 450K array combined with bisulfite and oxidative bisulfite treatment (BS/oxBS-450K). Paired 5-mC and 5-hmC beta values were generated using a custom pipeline of bioinformatics tools, and we modeled the effect of disease on paired 5-mC and 5-hmC data using a mixed effects beta regression model with a random effect for ID and an interaction term between disease category and DNA modification category (“5-mC” or “5-hmC”). We identified a number of CpG probes (AD: n=699, PD: total n = 80) that showed a significant interaction between disease status and DNA modification category (p-value < 2.4x10-7). Conclusions: While our PD data requires additional validation, our analyses suggest that there are widespread shifts in the balance between 5-mC and 5-hmC in Parkinson’s and Alzheimer’s disease.

2019-10-09 | GSE138597 | GEO

Quantitative sequencing of 5-methylcytosine and 5-hydroxymethylcytosine at single base resolution

Project description:To investigate the genomic levels of 5-hydroxymethylcytosine at single-base resolution. The current study developed a method which allows one to study hydroxymethylation of cytosines in the genome via a subtractive method of RRBS and oxidative RRBS.

2012-04-24 | E-MTAB-1042 | biostudies-arrayexpress

Brain 5-hydroxymethylcytosine alterations are associated with Alzheimer’s disease neuropathology

Project description:DNA 5-hydroxymethylcytosine (5hmC), also known as the sixth DNA base of the genome, plays an important role in neurogenerative disorders. However, little is known about its genome-wide distribution and its association with Alzheimer’s disease neuropathology. Here, we report a genome-wide profiling of 5hmC in 1,050 autopsied brains (dorsolateral prefrontal cortex) of older adults in the Religious Orders Study/Memory and Aging Project (ROSMAP) cohorts. This resource will facilitate future research of DNA methylation and demethylation in Alzheimer’s disease and other neurological disorders.

2025-03-07 | GSE291402 | GEO

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