DNA methylomes (internal data)

Welcome to MethylomeDB - the Brain Methylome Database. This database includes genome-wide DNA methylation profiles for human and mouse brains. The DNA methylation profiles were generated by Methylation Mapping Analysis by Paired-end Sequencing (Methyl-MAPS) method and analyzed by Methyl-Analyzer software package. The methylation profiles cover over 80% CpG dinucleotides in human and mouse brains in single-CpG resolution. The integrated genome browser (modified from UCSC Genome Browser allows users to browse DNA methylation profiles in specific genomic loci, to search specific methylation patterns, and to compare methylation patterns between individual samples.

Two species were included in the Brain Methylome Database: human and mouse. Human postmortem brain samples were obtained from three distinct cortical regions, i.e., dorsal lateral prefrontal cortex (dlPFC), ventral prefrontal cortex (vPFC), and auditory cortex (AC). Human samples were selected from our postmortem brain collection with extensive neuropathological and psychopathological data, as well as brain toxicology reports. The Department of Psychiatry of Columbia University and the New York State Psychiatric Institute have assembled this brain collection, where a validated psychological autopsy method is used to generate Axis I and II DSM IV diagnoses and data are obtained on developmental history, history of psychiatric illness and treatment, and family history for each subject. The mouse sample (strain 129S6/SvEv) DNA was collected from the entire left cerebral hemisphere.

The three human brain regions were selected because they have been implicated in the neuropathology of depression and schizophrenia. Within each cortical region, both disease and non-psychiatric samples have been profiled (matching subjects by age and sex in each group). Such careful matching of subjects allows one to perform a wide range of queries with the ability to characterize methylation features in non-psychiatric controls, as well as detect differentially methylated domains or features between disease and non-psychiatric samples. A total of 14 non-psychiatric, 9 schizophrenic, and 6 depression methylation profiles are included in the database (Table 1).

Table 1. Human sample information
Tissue/region Category Sample# Gender Age PMI (hour)
Brain dlPFC Control 4 2 male; 2 female 47±8 9.5±6.8
Brain dlPFC Schizophrenia 5 2 male; 3 female 41±15 10.4±4.8
Brain vPFC Control 6 3 male; 3 female 47±6 7.8±3.8
Brain vPFC Depression 6 3 male; 3 female 41±8 9.5±3.3
Brain AC Control 4 2 male; 2 female 47±8 7.0±2.8
Brain AC Schizophrenia 4 2 male; 2 female 39±17 9.0±4.2

Age-related DNA methylation (external data)

Hernandez et al. investigated DNA methylation changes between the ages of 1 and 102 years in human frontal cortex (Fctx), temporal cortex (Tctx), pons, and cerebellum (Crblm) (See the reference below). DNA methylation patterns were examined using Infiniumn HumanMethylation27 Beadchip (Illumina) which covers 27,578 CpG sites throughout the human genome. Their study identified CpG sites that show positive correlation between age and methylation. With the permission of the authors, we compiled DNA methylation profiles of the four brain regions from 90 subjects with the age ranging from 16 to 96. The 90 samples were divided into 8 age groups in approximately 10 year age intervals (Table 2). In the MethylomeDB Browser, we display average DNA methylation in each age group for the four brain regions.

Reference: Hernandez DG, Nalls MA, Gibbs JR, Arepalli S, van der Brug M, Chong S, Moore M, Longo DL, Cookson MR, Traynor BJ, Singleton AB. Distinct DNA methylation changes highly correlated with chronological age in the human brain. Hum Mol Genet. 2011 Mar 15;20(6):1164-72.

Table 2. Sample information for Singleton study
Sample# Gender Age
9 2 female; 7 male 16-20
13 3 female; 10 male 20-30
11 5 female; 6 male 30-40
26 10 female; 16 male 40-50
8 0 female; 8 male 50-60
5 0 female; 5 male 60-70
4 1 female; 3 male 70-80
14 6 female; 8 male 80-100