Measuring cell-type specific differential methylation in human brain tissue

Carolina M. Montaño, Rafael A. Irizarry, Walter E. Kaufmann, Konrad Talbot, Raquel E. Gur, Andrew P. Feinberg, Margaret A. Taub

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numberR94
JournalGenome biology
Volume14
Issue number8
DOIs
StatePublished - Aug 30 2013

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Keywords

  • Brain Region
  • Cell-Type Heterogeneity
  • DNA Methylation
  • Deconvolution
  • Differentially Methylated Region
  • Epigenetics
  • Fluorescence Activated Cell Sorting
  • Glia
  • Neun
  • Neuron
  • Postmortem Brain

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology

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