Société Française de Bioinformatique

Mots-Clés

Méthylation Epigénomique EWAS NMOSD MOGAD Sclérose en plaques

Description

Title: Identification of epigenetic signatures through DNA methylation analysis in neuroinflammatory diseases.
Context:
Neuromyelitis optica spectrum disorder (NMOSD) is a rare neuroinflammatory disease with unclear etiology. NMSOD is characterised (but not strictly limited to) by the presence of aquaporin-4 immunoglobulin G autoantibodies (AQP4-IgG), which target the water channel protein aquaporin-4 in the central nervous system. Some key clinical symptoms of NMOSD are visual defect/loss caused by optic neuritis, myelitis in the cervical and upper spinal cord, and many other brainstem syndrome symptoms.
In our project, multi-layer of omics analysis was performed to have a comprehensive view of the molecular architecture of the disease. CpG dinucleotide methylation is a key epigenetic mechanism at the interface between genes and the environment, playing a crucial role in regulating gene expression. Characterizing functional pathways and investigating how methylation patterns differ in blood cells between these pathologies could significantly deepen our understanding of the epigenetic alterations underlying neuroinflammatory disorders.
A first analysis was already performed, this internship will pursue the effort by including additional covariates.
Objective:
The main goal of this internship is to perform an epigenome-wide association study (EWAS) to compare DNA methylation profiles across patients with NMOSD (both AQP4-IgG positive and double seronegative), MOGAD, and Relapsing-Remitting Multiple Sclerosis (RRMS), compared to healthy controls.
Resource:
• Cohorts: Blood-derived samples from French and Swedish cohorts, including MOGAD, AQP4-IgG NMOSD, double-seronegative NMOSD, and RRMS patients.
• Technology: High-density data from Illumina Infinium Methylation EPIC v2.0.
• Tools: Analysis will be primarily conducted using R and the Bioconductor ecosystem (e.g., SesAMe, EpiDISH, etc.)
All the scripts and pipeline are also available
Missions:
- Differential Methylation Analysis to identify Differentially Methylated Positions (DMPs) and Differentially Methylated Regions (DMRs)
- Functional Annotation of identified sites (e.g., pathway enrichment analysis and gene target identification)
- Exploratory Data Analysis (e.g., PCA) to investigate sources of biological and technical variation
Skills:
- Expected:
• Proficiency in R programming (essential for methylation data analysis).
• Strong foundation in Statistics (linear models, false discovery rate/FDR control, etc.).
• Interest in Bioinformatics, Epigenetics, or Immunology.
• Good level in English (written and spoken)
- Appreciated :
• Prior experience with high-throughput sequencing or microarray data.
• Knowledge of neuroinflammatory disease mechanisms.