Methylome profiling of cell-free DNA during the early life course in (un)complicated pregnancies using MeD-seq: Protocol for a cohort study embedded in the prospective Rotterdam periconception cohort

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0310019 - e0310019

Published: Jan. 9, 2025

Introduction Placental DNA methylation differences have been associated with timing in gestation and pregnancy complications. Maternal cell-free (cfDNA) partly originates from the placenta could enable minimally invasive study of placental dynamics. We will for first time longitudinally investigate cfDNA during by using Methylated Sequencing (MeD-seq), which is compatible low levels has an extensive genome-wide coverage. aim to tissues different trimesters uncomplicated pregnancies, pregnancies placental-related complications, including preeclampsia fetal growth restriction. Identified gestational-age disease-specific differentially methylated regions (DMRs) lead numerous applications biomarker development. Methods analysis Our design involves three sub-studies. Sub-study 1 a single-centre prospective, observational subcohort embedded within Rotterdam Periconception cohort (Predict study). collect maternal plasma each trimester delivery, sample postpartum placentas (n = 300). In sub-study 2, we prospectively second 10 per trimester). 3 retrospectively after non-invasive prenatal testing (NIPT) independent validation case-control 30–60). A methylation-dependent restriction enzyme (LpnPI) be used generate fragments followed sequencing on Illumina NextSeq2000 platform. DMRs identified cell types, related or (Paired) profiles correlated aid tissue-of-origin analysis. establish score predict diseases. Discussion This provide insights dynamics health disease, clinical relevant biomarkers.

Language: Английский

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Blood DNA methylation signature for incident dementia: Evidence from longitudinal cohorts

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Distinguishing between molecular changes that precede dementia onset and those resulting from the disease is challenging with cross-sectional studies. We studied blood DNA methylation (DNAm) differences incident in two large longitudinal cohorts: Offspring cohort of Framingham Heart Study (FHS) Alzheimer's Disease Neuroimaging Initiative (ADNI) study. analyzed DNAm samples > 1000 cognitively unimpaired subjects. Meta-analysis identified 44 CpGs differentially methylated regions consistently associated time to both cohorts. Our integrative analysis early processes dementia, such as immune responses metabolic dysfunction. Furthermore, we developed a methylation-based risk score, which successfully predicted future cognitive decline an independent validation set, even after accounting for age, sex, apolipoprotein E ε4, years education, baseline diagnosis, Mini-Mental State Examination score. offers promising source biomarker assessment. Blood at individual are significantly dementia. Pathway revealed enriched biological pathways involved processes. Out-of-sample demonstrated score dataset,

Language: Английский

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Evaluation of Illumina and Oxford Nanopore Sequencing for the Study of DNA Methylation in Alzheimer’s Disease and Frontotemporal Dementia

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4198 - 4198

Published: April 28, 2025

DNA methylation is a critical epigenetic mechanism involved in numerous physiological processes. Alterations patterns are associated with various brain disorders, including dementias such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Investigating these alterations essential for understanding the pathogenesis progression of disorders. Among methods detecting methylation, sequencing one most widely employed. Specifically, two main approaches commonly used analysis: bisulfite single-molecule long-read sequencing. In this review, we compared performances CpG detection obtained using popular platforms, Illumina Oxford Nanopore (ON) Our comparison considers several factors, accuracy, efficiency, genomic regions, costs, wet-lab protocols, bioinformatics pipelines. We provide insights into strengths limitations both particular focus on their application research AD FTD.

Language: Английский

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Blood DNA Methylation Signature for Incident Dementia: Evidence from Longitudinal Cohorts

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

ABSTRACT INTRODUCTION Distinguishing between molecular changes that precede dementia onset and those resulting from the disease is challenging with cross-sectional studies. METHODS We studied blood DNA methylation (DNAm) differences incident in two large longitudinal cohorts: Offspring cohort of Framingham Heart Study (FHS) Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. analyzed DNAm samples over 1,000 cognitively unimpaired subjects. RESULTS Meta-analysis identified 44 CpGs differentially methylated regions consistently associated time to both cohorts. Our integrative analysis early processes dementia, such as immune responses metabolic dysfunction. Furthermore, we developed a Methylation-based Risk Score, which successfully predicted future cognitive decline an independent validation set, even after accounting for age, sex, APOE ε4, years education, baseline diagnosis, MMSE score. DISCUSSION offers promising source biomarker detection dementia.

Language: Английский

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