Background

Epigenetic modifications confer stable transcriptional patterns in the brain, and both normal and abnormal brain function involve specialized brain regions.

Methods

We examined DNA methylation by whole-genome bisulfite sequencing in neuronal and non-neuronal populations from four brain regions (anterior cingulate gyrus, hippocampus, prefrontal cortex, and nucleus accumbens) as well as chromatin accessibility in the latter two.

Results

We find pronounced differences in both CpG and non-CpG methylation (CG-DMRs and CH-DMRs) only in neuronal cells across brain regions. Neuronal CH-DMRs were highly associated with differential gene expression, whereas CG-DMRs were consistent with chromatin accessibility and enriched for regulatory regions. These CG-DMRs comprise ~12 Mb of the genome that is highly enriched for genomic regions associated with heritability of neuropsychiatric traits including addictive behavior, schizophrenia, and neuroticism, thus suggesting a mechanistic link between pathology and differential neuron-specific epigenetic regulation in distinct brain regions.

v1.2: Added new option -genome version (GRCh37, GRCh38)

1.   Workflow Selection

In the current version, multiple functions are integrated in the work flow "Differential Methylation Analysis".

2.   Customized Parameter

1). "Project name"

Give your analysis a name, it will serve as the recognizable name “Job Name” in “My Jobs - Results”.

1). "Data From": "DRS", "Local", "Web"
Location of data to be analyzed.

Location of data to be analyzed.

Web = Only upload the data temporarily for analysis;

DRS = Data stored in the Data Repository Storage already;

2). "DRS ID"
If "Local" OR "Web" is selected in "Data From", you need to fill in the corresponding ID here.

3). "Seq Read Type": "Single_end", "Paired_end"
This sample is single-ended sequencing reads or paired-end sequencing reads.

4). "File Name"
Filename of the data to be analyzed.
If the data contains only a single file (such as single-end sequencing data or .sra suffix file), just fill in the file name here; if the data contains multiple files (such as paired-end sequencing data file_{1,2}.fq. gz), you need to fill in here and "FilenameR2" at the same time.

5). "File Name R2"
If the data contains multiple files (such as paired-end sequencing data file_{1,2}.fq.gz), you need to fill in here and "Filename" at the same time.
6). "Sample Group": "Case", "Control"
The group of this sample.

7). "QC": "yes", "no"
Whether to perform data quality control. It is recommended to select "yes" unless the data has been trimmed.
8). "Genome Version": "GRCh38", "GRCh37"
Genome Version.

9). "Seq Region": "RRBS", "WGBS", "Target"
The sequencing area of this sample is RRBS (MspI enzyme), WGBS, or Targeted bisulfite sequencing.

10). "File Format": "sra", "fq", "fq.gz", "fastq", "fastq.gz"
File format of this sample.
11). "Sample ID"
Customize the name for each sample. It will appear in the figures and table results as the sample identifier.

An Example of Customized Parameter:

1). "core" (Under development)
Number of cores applied for in your task.

· Others (Under development)

3. Upload Data

You need to compress the file which filled in “Data” into the corresponding format according to the following requirements.

a. If the data to be analyzed is not stored on our platform, only upload the data temporarily (Web) to use the analysis function. Please compress all the data to be analyzed into a single file, supported compression formats: rar, zip, gz, tar.gz.

b. If the data to be analyzed has been stored on our platform, including Data Repository Storage (DRS), or stored in the HPC@SJTU through the administrator (Local), please upload any content compressed file that conforms to these formats: rar, zip, gz, tar.gz.