ASAP Human Postmortem-Derived Brain Sequencing Collection

ASAP Human Postmortem-Derived Brain Sequencing Collection

The Aligning Science Across Parkinson’s (ASAP) initiative, Allen Institute, and the Michael J. Fox Foundation are teaming up to help researchers unlock deeper insights into how cell types, brain anatomy, and diseases like Parkinson’s are connected. 

Together we will annotate, enhance and add knowledge to the growing data catalog in the ASAP CRN Cloud through integration of cell type taxonomies using the Allen Institute’s MapMyCells tool and visualization through the Allen Brain Cell (ABC) Atlas web application. This integration of data and knowledge allows users to visualize and explore the changes in gene expression of specific, highly resolved brain cell types in the context of a large Parkinson’s disease cohort of donors.

About the data

This initial collaboration focuses on the Human Postmortem-derived Brain Sequencing Collection (PMDBS), a harmonized repository comprised of single nucleus and PolyA RNA-seq data contributed by five ASAP CRN teams (Hafler, Lee, Jakobsson, Scherzer, Hardy). Sequencing data were uniformly aligned to the GRCh38.p13 reference genome (Gencode V32), quality control was performed and low-quality cells were filtered out. A set of highly variable genes were identified and the scVI workflow resulted in an integrated latent variable representation, 2D UMAP coordinates and a set of 30 clusters. Currently, the repository spans roughly 3 millions cells obtained from 9 brain regions and 211 donors with various pathologies (including healthy control). For more details on this dataset and to access the raw data used in its preparation, please visit the collection description on the ASAP CRN Cloud webpage.

Learn more about the curation of this data set: ASAP CRN Cloud PMDBS snRNAseq Quality Control Dimension Reduction 

ASAP-PMDBS cells were mapped to the whole human brain (WHB) taxonomy (Siletti et al., 2023), which is hierarchical taxonomy of ~3.3 million cells (neurons and non-neuronal cells) with 31 superclusters, 461 clusters, and 3,313 subclusters spanning 105 anatomical dissections across the whole human brain. The 30 ASAP clusters were mapped at the WHB supercluster, cluster, and subcluster levels. Click the button below to view the datasets side-by-side.

Explore the data in the ABC Atlas

Additional resources

• Guided exploration of ASAP-PMDBS data in the ABC Atlas

• MapMyCells Results (ASAP-PMDBS cells to the WHB and SEA-AD MTG taxonomies)

• Compare taxonomies using the Annotation Comparison Explorer (Annotation table: ASAP CRN cell info subsample.csv.gz)

Data access

The simplified data created by the Allen Institute for Brain Science in the form of expression matrices and associated metadata are available in an AWS S3 bucket, through the Open Data on AWS program:

Data is being shared under the CC BY 4.0 license.

Associated notebooks

• Getting started: learn how to use the manifest.json file to facilitate data download and usage.

• Accessing 10X gene expression data: learn how to load individual genes from the 10X expression data.

• ASAP Data Overview: Learn about the ASAP-PMDBS harmonized, single cell dataset including disease indicators and UMAP.

• Mapping to the Whole Human Brain Taxonomy: Explore the mapping of the ASAP-PMDBS cells to the Siletti, Whole Human Brain (WHB) taxonomy produced by MapMyCells.

• Mapping to the SEA-AD MTG Taxonomy: Explore the mapping of the ASAP-PMDBS cells to the SEA-AD, Whole Human Brain taxonomy produced by MapMyCells.

• 10X Gene Expression: Learn how to extract gene expression data for specific genes and visualize them in a UMAP.