Chromatin accessibility tracks on UCSC genome browser

Follow the instructions below to create a new Track Hub Session.

  • Copy this link to our UCSC track hub file.
  • Navigate to the UCSC Genome Browser.
  • On the toolbar go to My Data, and click Track Hubs in the dropdown menu.
  • Paste the link that you copied previously into the URL bar, and click the Add Hub button.
  • Finally, go back to the Track Hubs page you should see a new Track Hub called AD_NatGen_2021. Click the link on the right labeled hg38 under Assemblies and you should be directed to the Track Hub.

Raw and processed snATAC-seq, snRNA-seq, and bulk RNA-seq datasets are available on Synapse and GEO.

All code used to analyzed the data can be found at our github repository.

Single-nucleus chromatin accessibility and transcriptomic characterization of Alzheimer's disease

Abstract

The gene-regulatory landscape of the brain is highly dynamic in health and disease, coordinating a menagerie of biologi- cal processes across distinct cell types. Here, we present a multi-omic single-nucleus study of 191,890 nuclei in late-stage Alzheimer’s disease (AD), accessible through our web portal, profiling chromatin accessibility and gene expression in the same biological samples and uncovering vast cellular heterogeneity. We identified cell-type-specific, disease-associated candidate cis-regulatory elements and their candidate target genes, including an oligodendrocyte-associated regulatory module contain- ing links to APOE and CLU. We describe cis-regulatory relationships in specific cell types at a subset of AD risk loci defined by genome-wide association studies, demonstrating the utility of this multi-omic single-nucleus approach. Trajectory analy- sis of glial populations identified disease-relevant transcription factors, like SREBF1, and their regulatory targets. Finally, we introduce single-nucleus consensus weighted gene coexpression analysis, a coexpression network analysis strategy robust to sparse single-cell data, and perform a systems-level analysis of the AD transcriptome.