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Measuring cell-type specific differential methylation in human brain tissue

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2013

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BioMed Central
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Montaño, Carolina M, Rafael A Irizarry, Walter E Kaufmann, Konrad Talbot, Raquel E Gur, Andrew P Feinberg, and Margaret A Taub. 2013. “Measuring cell-type specific differential methylation in human brain tissue.” Genome Biology 14 (8): R94. doi:10.1186/gb-2013-14-8-r94. http://dx.doi.org/10.1186/gb-2013-14-8-r94.

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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.

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DNA methylation, epigenetics, differentially methylated region, brain region, cell-type heterogeneity, deconvolution, NeuN, neuron, glia, postmortem brain, fluorescence activated cell sorting

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