Genomics

Dataset Information

43

Deconvolution of whole blood DNA methylomes reveals immune cell type-specific differential methylation in Multiple Sclerosis


ABSTRACT: Whole blood is a highly convenient and informative tissue from which to sample DNA and RNA in epigenomic and functional genomic studies, but it is comprised of multiple distinct cell types and this complexity significantly impairs our ability to interpret downstream differential methylation and/or differential expression results. In this multiple sclerosis (MS)-focused study we utilised an application of current statistical deconvolution methods to interrogate whole blood DNA methylation data thereby enabling the methylome of several immune cell types to be analysed independently. Methylome profiling on cell type-purified blood samples revealed optimal CpG sets for use as robust immune cell markers in the statistical deconvolution process. We show that it is possible to identify differentially methylated (DM) loci in a cell type specific manner using statistical deconvolution. Finally, we demonstrate that deconvolution improved the biological relevance and interpretability of our DM results, significantly enhancing concordance of the identified DM loci with loci previously shown to be genetically or epigenetically associated with MS. Overall design: Case-Control design with whole blood methylomes of 14 healthy controls and 13 Multiple Sclerosis affected cases (1 failed bisulphite conversion) assayed. In addition, 8 of the healthy controls also have cell-type purified samples of neutrophils, CD4+ T cells, CD8+ T cells, NK cellsa, B cells and monocytes individually assayed.

INSTRUMENT(S): Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)

SUBMITTER: Andrew David Fox  

PROVIDER: GSE88824 | GEO | 2017-06-30

SECONDARY ACCESSION(S): PRJNA348735

REPOSITORIES: GEO

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