title: Measuring cell-type specific differential methylation in human brain tissue.
abstract: The behavior of epigenetic mechanisms in the brain is obscured by tissue heterogeneity and disease-related histological changes. Not accounting for these confounders leads to biased results. We develop a statistical methodology that estimates and adjusts for celltype composition by decomposing neuronal and non-neuronal differential signal. This method provides a conceptual framework for deconvolving heterogeneous epigenetic data from postmortem brain studies. We apply it to find cell-specific differentially methylated regions between prefrontal cortex and hippocampus. We demonstrate the utility of the method on both Infinium 450k and CHARM data.
authors.forename: Carolina M
authors.initials: CM
authors.lastname: Montaño
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Irizarry
authors.forename: Walter E
authors.initials: WE
authors.lastname: Kaufmann
authors.forename: Konrad
authors.initials: K
authors.lastname: Talbot
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Taub
mesh_terms: D000465:Algorithms; D001344:Autopsy; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000706:statistics & numerical data*; D009928:Organ Specificity; D017397:Prefrontal Cortex / Q000166:cytology / Q000378:metabolism*