ROSMAP CUIMC snRNA-seq expression#

Religious Orders Study (ROS) or the Rush Memory and Aging Project (MAP) single-nucleus RNA-seq expression data from Columbia University Irving Medical Center (CUIMC).

Please refer to this document for an overview of the ROSMAP project.

Contact#

Anjing Liu

Contact Affiliation : Columbia University

Contact Role : Anjing Liu performed pseudo-bulk expression preprocessing and QTL analysis

Study Overview#

Grant number : U01AG061356, RF1AG057473, U01AG046152, R01AG066831, U01AG072572

Publication : PMID: 38514782

Acknowledgement : Study data were generated from postmortem brain tissue provided by the Religious Orders Study and Rush Memory and Aging Project (ROSMAP) cohort at Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago. This work was funded by NIH grants U01AG061356 (De Jager/Bennett), RF1AG057473 (De Jager/Bennett), and U01AG046152 (De Jager/Bennett) as part of the AMP-AD consortium, as well as NIH grants R01AG066831 (Menon) and U01AG072572 (De Jager/St George-Hyslop).

Study name : ROSMAP CUIMC snRNA-seq expression

Study Description : Single-nucleus RNA-seq expression data from 424 ROSMAP donors generated at Columbia University Irving Medical Center (CUIMC) by the De Jager lab. Nuclei were isolated from dorsolateral prefrontal cortex (DLPFC) postmortem brain tissue and profiled using droplet-based 10x Genomics snRNA-seq. Cell types covered: Astrocytes (Ast), Excitatory neurons (Exc), Inhibitory neurons (Inh), Microglia (Mic), Oligodendrocytes (Oli), and Oligodendrocyte progenitor cells (OPC). Pseudo-bulk expression matrices were generated per cell type for use in cis-eQTL analysis.

Disease : Alzheimer’s Disease

Data Citation : Omics data: https://www.synapse.org/Synapse:syn31512863

Genetics data: https://dss.niagads.org/datasets/ng00067/

Genetics Publication : PMID: 40407102

PI : Phil De Jager (Columbia University)

Dataset Description#

Raw data#

Nuclei were isolated from DLPFC postmortem brain tissue of 424 ROSMAP participants. Single-nucleus RNA-seq was performed using the 10x Genomics Chromium platform. Raw sequencing reads were aligned to the GRCh38 reference genome. The primary data release is available on Synapse at syn31512863.

Molecular phenotype matrices#

Pseudo-bulk count matrices were generated by aggregating UMI counts across nuclei within each cell type per donor. Six major brain cell types are included: Astrocytes (Ast), Excitatory neurons (Exc), Inhibitory neurons (Inh), Microglia (Mic), Oligodendrocytes (Oli), and Oligodendrocyte progenitor cells (OPC).

Phenotype preprocessing#

Pseudo-bulk expression matrices were normalized and filtered following standard pipelines. Genes with low expression were excluded. Normalized expression values were prepared for use as molecular phenotypes in cis-eQTL mapping via the ADSP FGC xQTL pipeline. Covariates for eQTL analysis include sex, age at death, postmortem interval (PMI), study (ROS or MAP), total genes detected, top genotype principal components, and expression principal components.

Analysis Status#

Pseudo-bulk expression preprocessing: Finished.

QTL Analysis#

QTL analysis for this dataset is documented in ../../qtl/eQTL/ROSMAP_snRNAseq_pseudo_bulk_qtl.md.

Flagship paper analyses: