careennaitore / ms_epigenomics

Identifying Methylation Sites and Interfering RNAs in Multiple Sclerosis Patients Using Human DNA-seq and RNA-seq

Identifying Differentially Expressed Genes, Methylation Sites and Interfering RNAs in Human Genome in relation to pathologies : Application on Multiple Sclerosis Patients

The Project aim:

Creat an R  script that perform a full genomic, transcriptomic and methylation study and filter the target gene specific data .

Several researche have proved that the genomic, transcriptomic and the methylation profils are affected with environmental factors, which creat different prevalence area around the world,

Different prevalence:

To solve the problem of different prevalence that can be correlated with different genomic, transcriptomic and epigenomic profiles; In this study, we will use data from each prevalence area.

Workflow

Result

The genetic specific data will be automatically exported in the  working directory folder as 4 txt files:

• The gene expression profile : p value and LogFC

• If the gene is : overexpressed , underexpressed or not differentially expressed.

• List of the  CpG sites that are methylated in the gene specific promoter with supplementary data mainly the B value , DMR (differential methylation or not ), and the relation to Cpg island

• List of miRNAs that target the gene in healthy condition

• Are these miRNA expressed in disease group or not ( the user need to search for each miRNA separately ).

Case study

In order to validate the tool developed in this work, we applied the analysis to STAT3 gene which is implicated in the pathology of MS.

in order to identify methylated regions and miRNAs susceptible to interact with this gene.

The case study result are availbul in the manuscript.

Suplementary data

All processed not filtered data are provided as supplementary files , so the user can define different settings. Option 1 : Change the p value to define Differencially expressed genes ( the p value used is <0.05) Option 2 : In the case study we used cpg that exist in the promoter region. Supplementary files are provided for "gene associated cpgs " and "non gene asssociated cpgs"

More information are available in : Reproducibility guide.pdf part 1

Workflow reproducibility

The work flow could be reproduced for other pathologies data available on GEO database. More information are available in : Reproducibility guide.pdf part 2

References

1. Dupont C, Armant DR, Brenner CA. (2009), “Epigenetics: definition, mechanisms and clinical perspective”. Semin Reprod Med.;27(5):351-7. doi: 10.1055/s-0029-1237423. Epub 2009 Aug 26. PMID: 19711245; PMCID: PMC2791696.

2. Eslahi, Maede & Nematbakhsh, Negin & Dastmalchi, Narges & Teimourian, Shahram & Safaralizadeh, Reza., (2022). “An Updated Review of Epigenetic-Related Mechanisms and Their Contribution to Multiple Sclerosis Disease”. CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders). 10.2174/1871527321666220119104649.

3. Wang, H., Li, Y., Ryder, J.W. et al. (2013), “Genome-wide RNAseq study of the molecular mechanisms underlying microglia activation in response to pathological tau perturbation in the rTg4510 tau transgenic animal model”. Mol Neurodegeneration 13.

4. Dharshini S. Akila Parvathy, Jemimah Sherlyn, Taguchi Y. H., Gromiha M. Michael (2021), “Exploring Common Therapeutic Targets for Neurodegenerative Disorders Using Transcriptome Study “, Frontiers in Genetics volume 12.

5. Moore LD, Le T, Fan G. (2013), “DNA methylation and its basic function”. Neuropsychopharmacology.

6. Hop, PJ Luijk, RDaxinger, L. et al. (2020), “Genome-wide identification of genes regulating DNA methylation using genetic anchors for causal inference”. Genome Biol 21, 220.

Contact for data update

Tech leader : Hiba Ben Aribi email : [email protected]

Team

Guerbouj Souheila,Phd in Genetics and molecular biology ,UTM

Hiba Ben Aribi, Master in Neuroscience and Biotechnology , UTM

Farah Ayadi, Master in molecular biology ,UTM

Careen Naitore,Master in Bioinformatics and molecular biology, JKUAT