The three-dimensional landscape of chromatin accessibility in Alzheimer's disease
Mads E Hauberg,
James M Vicari,
Steven P Kleopoulos,
Sarah M Reach,
Ralph A Nixon,
Gabriel E. Hoffman,
John F. Fullard,
Posted 12 Jan 2021
bioRxiv DOI: 10.1101/2021.01.11.426303
Posted 12 Jan 2021
Much is still unknown about the neurobiology of Alzheimer's disease (AD). To better understand AD, we generated 636 ATAC-seq libraries from cases and controls to construct detailed genome-wide chromatin accessibility maps of neurons and non-neurons from two AD-affected brain regions, the entorhinal cortex and superior temporal gyrus. By analyzing a total of 19.6 billion read pairs, we expanded the known 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. Using inter-individual variation in chromatin accessibility, we define cis-regulatory domains capturing the 3D structure of the genome. Multifaceted analyses uncovered disease associated perturbations impacting chromatin accessibility, transcription factor regulatory networks and the 3D genome, and implicated transcriptional dysregulation in AD. Overall, we applied a systematic approach to understand the role of the 3D genome in AD and to illuminate novel disease biology that can advance diagnosis and therapy.
- Downloaded 609 times
- Download rankings, all-time:
- Site-wide: 45,141
- In neuroscience: 6,414
- Year to date:
- Site-wide: 4,433
- Since beginning of last month:
- Site-wide: 9,827
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!