Single-nucleus alternative polyadenylation repository
Overview
This is a supplementary website for: Single-cell profiling and genetic regulation of alternative polyadenylation in the human brain
We report a single-nucleus atlas of alternative polyadenylation (APA) of the aged human brain across 2 million cells from 379 human post-mortem brains across aged individuals with and without Alzheimer’s disease (AD).
We also integrate APA variation with whole genome sequencing (WGS) to identify cell-type-resolved 3’UTR quantitative trait loci (3’aQTLs) for 4,288 APAs. We find that 3’aQTLs preferentially colocalize with pQTLs over eQTLs. This extends to 168 GWAS and 3’aQTL colocalized loci, of which only 17.5% are shared with eQTLs. APA provides a complementary and largely independent mechanistic layer both for understanding gene regulatory changes in disease, as well as for interpreting non-coding genetic variation in brain traits and diseases.
- Summary analyses are currently available as supplementary tables below.
- Analysis code for the paper can be found on github
- RNA-seq data for the knock-down experiments for regulator validation are available at National Genomics Data Center (NGDC) under the accession HRA014304
- In addition to resources provided below and on Synapse, the original single-cell transcriptomic dataset is available for interactive visualization through the UCSC Cell Browser, as part of the AD and Aging brain atlas
Contact: Xushen Xiong - xiongxs at zju dot edu dot cn / Carles Boix - carles_boix at hms dot harvard dot edu
Datasets
Datasets corresponding to manuscript analyses can be found here and are summarized in the table below. Processed human datasets have been deidentified to protect confidentiality - the mapping to ROSMAP IDs and complete metadata can be found on Synapse.
| Dataset | Files | Description |
|---|---|---|
| Individual metadata | Table (tsv) | De-identified individual-level metadata from aging and AD atlas |
| APA definitions | Table (tsv, rds) | APA definitions and mean PDUI values across cell types |
| Individual-level APA matrices | Directory with rds files | Individual-level APA matrices (PDUI values) for each cell type |
| AD differential APAs (DAPAs) | Table (tsv, xlsx) | Differential APAs associated with Alzheimer’s disease status in each cell type. Genes are annotated with AD risk gene status, 3’aQTL status, and AD GWAS colocalization status |
| 3’aQTL and eQTL summary statistics | Directory with sumstat files | Summary statistics for 3’aQTL and eQTL mapping in each cell type |
| Genetically regulated APAs | Tables (tsv, xlsx) | Merged table of all APA sites with genetic regulation (g-APA) in each cell type, identified through 3’aQTL mapping |
Complete human raw data were released as part of the AD and Aging brain atlas in collaboration with ROSMAP through Synapse (syn52293442). The data and human metadata must be accessed through Synapse with a Data Use Certificate (DUC). Human metadata can be found at Synapse (syn3157322) or can be requested through the RADC Hub.