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The three-dimensional landscape of chromatin accessibility in Alzheimer's disease

Abstract

To better understand the neurobiology of Alzheimer’s disease, we used ATAC-seq to profile chromatin accessibility in a total of 636 samples spanning two brain regions and two cell types, from both cases and controls. By analyzing a total of 19.6 billion read pairs, we expanded the repertoire of regulatory sequences in the human brain. Multi-omic data integration associated global patterns of chromatin accessibility with gene expression and identified cell-specific enhancer-promoter interactions. We utilized interindividual variation in chromatin accessibility to define cis-regulatory domains that capture the 3D structure of the genome. Multifaceted analyses uncovered disease perturbations impacting chromatin accessibility, transcription factor regulatory networks and the 3D genome, and implicated transcriptional dysregulation in Alzheimer’s disease. Overall, we applied a systematic approach to understand the role of the 3D genome in Alzheimer’s disease and to illuminate novel disease biology that can advance diagnosis and therapy.

Data: Raw data & UCSC hub

Raw and processed data are available at Synapse. You can also view the open chromatin tracks in the UCSC genome browser as a track hub. OCR:
Description of UCSC tracks:
 


Interactive data visualisation

Clustering of samples by their chromatin accessibility using t-SNE & differentially accessible OCRs for AD-related phenotype case/control (control is CERAD=1, case is CERAD=2,3,4). Move cursor over the data points to see full description.
© 2020 Roussos Lab at Icahn School of Medicine at Mount Sinai