Created by Jessica Johnson
Icahn School of Medicine at Mount Sinai - logo

BOCA2: Lineage-specific Brain Open Chromatin Atlas

The chromatin landscape of human brain cells encompasses key information to understanding brain function. Here we use ATAC-seq to profile the chromatin structure in four distinct populations of cells (glutamatergic neurons, GABAergic neurons, oligodendrocytes, and microglia/astrocytes) from three different brain regions (anterior cingulate cortex, dorsolateral prefrontal cortex, and primary visual cortex) in human postmortem brain samples. We find that chromatin accessibility varies greatly by cell type and, more moderately, by brain region, with glutamatergic neurons showing the largest regional variability. Transcription factor footprinting implicates cell-specific transcriptional regulators and infers cell-specific regulation of protein-coding genes, long intergenic noncoding RNAs and microRNAs. In vivo transgenic mouse experiments validate the cell type specificity of several of these human-derived regulatory sequences. We find that open chromatin regions in glutamatergic neurons are enriched for neuropsychiatric risk variants, particularly those associated with schizophrenia. Integration of cell-specific chromatin data with a bulk tissue study of schizophrenia brains increases statistical power and confirms that glutamatergic neurons are most affected. These findings illustrate the utility of studying the cell-type-specific epigenome in complex tissues like the human brain, and the potential of such approaches to better understand the genetic basis of human brain function.

Data: UCSC hub

You can view the open chromatin tracks in the UCSC genome browser as a track hub by clicking these links:
  • 4 cell-lines (recommended): hg19 hg38
  • 4 cell-lines in 3 brain regions (advanced): hg19 hg38

Data: Downloads and individual tracks

You can view or download the individual files as individual tracks by following the links below. Be aware that the downloadable files are large (approximately 110GB in total). You can also access the GEO page for access to the individual sample data here.

Cell type Track download hg19 Track download hg38
  Merged ACC DLPFC PVC Merged ACC DLPFC PVC
Glutamatergic neurons Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file
GABAergic neurons Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file
Oligodendrocytes Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file
Microglia and astrocytes Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file Download bigWig file

Deconvolution example

Example of using our reference panel for deconvolution of cell type proportions in bulk tissue can be downloaded here. Before running the whole code, please set the path to the main directory in headline of example_deconvolution.R - variable ROOT.

Interactive data visualisation

Clustering of samples by their chromatin accessibility using t-SNE. Move cursor over the data points to see full description.
© 2020 Roussos Lab at Icahn School of Medicine at Mount Sinai