ROSMAP MIT snRNA-seq expression#

Religious Orders Study (ROS) or the Rush Memory and Aging Project (MAP) single-nucleus RNA-seq expression data from Massachusetts Institute of Technology (MIT).

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 : AG058002, AG062377, NS110453, NS115064, AG062335, AG074003, NS127187, MH119509, HG008155, RF1AG062377, RF1AG054321, RO1AG054012, GM087237, P30AG10161, P30AG72975, R01AG15819, R01AG17917, U01AG46152, U01AG61356

Publication : PMID: 39048816, PMID: 37774677

Acknowledgement : The results published here are in whole or in part based on data obtained from the AD Knowledge Portal (https://adknowledgeportal.org/). 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 supported in part by the Cure Alzheimer’s Fund, NIH grants AG058002, AG062377, NS110453, NS115064, AG062335, AG074003, NS127187, MH119509, HG008155 (M.K.), RF1AG062377, RF1AG054321, RO1AG054012 (L.-H.T.) and the NIH training grant GM087237 (to C.A.B.). ROSMAP is supported by P30AG10161, P30AG72975, R01AG15819, R01AG17917, U01AG46152, U01AG61356.

Study name : ROSMAP MIT snRNA-seq expression

Study Description : Single-nucleus RNA-seq expression data from 427 ROSMAP donors generated at Massachusetts Institute of Technology (MIT) by the Kellis lab. Nuclei were isolated from prefrontal cortex (PFC) postmortem brain tissue and profiled using 10x Genomics snRNA-seq to generate a comprehensive single-cell atlas of the aged human prefrontal cortex spanning more than 2.3 million nuclei. 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:syn52293417

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

Genetics Publication : PMID: 40407102

PI : Manolis Kellis (Massachusetts Institute of Technology)

Dataset Description#

Raw data#

Nuclei were isolated from prefrontal cortex postmortem brain tissue of 427 ROSMAP participants spanning the full spectrum of AD pathology (Braak stages 0–VI). Single-nucleus RNA-seq was performed using the 10x Genomics Chromium platform. Raw sequencing reads were aligned to the GRCh38 reference genome following the MIT preprocessing workflow described in Mathys et al. (2023). The primary data release is available on Synapse at syn52293417.

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: