Measuring cell-type specific differential methylation in human brain tissue

Genome Biology

Margaret A Taub⁶  Andrew P Feinberg⁴  Raquel E Gur²  Konrad Talbot²  Walter E Kaufmann⁵  Rafael A Irizarry¹  Carolina M Montaño³ 

[1] Dana Farber Cancer Institute, Department of Biostatistics and Computational Biology, 450 Brookline Avenue, Boston, MA 02215, USA;Department of Psychiatry, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA;Predoctoral Training Program in Human Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 733 N Broadway, Baltimore, MD 21205, USA;Center for Epigenetics, Johns Hopkins University School of Medicine, 855 N Wolfe Street, Baltimore, MD 21205, USA;Department of Neurology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA;Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe Street, Baltimore, MD 21205, USA

关键词: fluorescence activated cell sorting;    postmortem brain;    glia;    neuron;    NeuN;    deconvolution;    cell-type heterogeneity;    brain region;    differentially methylated region;    epigenetics;    DNA methylation;   

Others  :  864012
DOI  :  10.1186/gb-2013-14-8-r94

 received in 2013-03-07, accepted in 2013-08-30,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Montaño et al.; licensee BioMed Central Ltd.

【 图 表 】

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