Journal
GENOME BIOLOGY
Volume 14, Issue 8, Pages -Publisher
BMC
DOI: 10.1186/gb-2013-14-8-r94
Keywords
DNA methylation; epigenetics; differentially methylated region; brain region; cell-type heterogeneity; deconvolution; NeuN; neuron; glia; postmortem brain; fluorescence activated cell sorting
Funding
- NIH [U01 MH085270, R01 GM083084]
- Department of Defense (CDMRP) [AR080125]
- NIAMS [P30AR053503]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [P30HD018655] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [P30AR053503] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM083084] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [U01MH085270] Funding Source: NIH RePORTER
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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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