Decoding the multiregional atlas of Parkinson’s disease at single-cell resolution
This web app provides an interactive interface for exploring the transcriptomic results from a multiregional single-nucleus RNA-seq study of Parkinson's disease (PD). Browse donor-level gene expression profiles, differential expression patterns and functional enrichment summaries across 5 brain regions and 22 cell subtypes from the AMP-PDRD cohort (93 donors; 2.28 million nuclei).
For details on the methodology behind each result, refer to the preprint and the 'About' section. Additionally, hovering over labels and controls within each explorer reveals additional information.
Read the preprint
Funding
- FEDER / Junta de Andalucía — ProyExcel_00978
- MICIU / AEI / FEDER — PID2023-152976NB-I00
- FPU23/01866, Spanish Ministry of Universities (J.A. Tejedor-Serrano)
- RYC2024-049532-I, MICIU/AEI + ESF+ (J. Martorell-Marugán)
- JDC2024-053114-I, MICIU/AEI + ESF+ (Á. Arzalluz-Luque)
Expression profiles (CPM) explorer
Explore donor-level expression patterns across cell types, regions and covariates of interest.
Differential gene expression (DGEA) explorer
Explore differential gene expression between Parkinson’s disease (PD) and healthy controls across cell types and brain regions.
GSEA explorer
Survey Parkinson's disease versus control enrichment patterns across regions, databases and ranked gene sets with coordinated overview plots.
Methods
Expression profiles (CPM)
Pseudobulk count profiles were generated by aggregating raw counts per donor, cell subtype and brain region using
decoupleR
(
mode = "sum"
).
Library sizes were normalized with
TMMwsp
via
edgeR::calcNormFactors()
. Counts per million (CPM) values are visualized at the donor level, stratified by the user-selected covariate (disease status, sex, cohort, age at baseline or post-mortem interval).
Differential gene expression (DGEA)
Pseudobulk differential expression analysis was performed with
limma/voom
comparing PD donors against healthy controls. A linear model was fitted using
limma::voomLmFit()
with precision weighting (
sample.weights = TRUE
)
and a donor random effect (
block = participant_id
) to account for multiple brain regions per individual. The model formula was:
~ group + scale(log(1 + lib.size)) + scale(age at death) + scale(PMI) + sex + brain bank
where
group
encodes the brain region × disease status interaction. FDR correction was applied per contrast (Benjamini-Hochberg).
Functional profiling (GSEA)
Gene Set Enrichment Analysis (GSEA) was performed with
clusterProfiler
(
GSEA()
)
on genes ranked by log₂ fold change from the DGEA results.Gene sets were obtained from the Molecular Signatures Database (MSigDB) via
msigdbr
, covering: Hallmark, GO (BP / CC / MF), KEGG Legacy, KEGG Medicus, Reactome, WikiPathways, miRNA (miRDB) and TF targets (GTRD).
Data & Disclaimer
Data source: Single-nucleus RNA-seq data were obtained from the Accelerating Medicines Partnership® Parkinson’s Disease and Related Disorders (AMP-PDRD) Knowledge Platform, v4.0 ‘Postmortem Sequencing Data’ (download date: 2024). Access to AMP-PDRD data requires an approved data access request at www.amp-pdrd.org .
Human subjects: All analyses use post-mortem human brain tissue data generated by the Mount Sinai Brain Bank, University of Miami Brain Endowment Bank, Harvard Brain Tissue Resource Center, and the Udall Center of Excellence for Parkinson’s Disease Research, accessed via the AMP-PDRD platform.
Acknowledgement: Data used in the preparation of this article were obtained from the Accelerating Medicine Partnership® (AMP®) Parkinson’s Disease (AMP PD) and Parkinson’s Disease & Related Disorders (AMP PDRD) Knowledge Platform. For up-to-date information on the study, visit www.amp-pdrd.org .
The AMP® PD program is a public-private partnership managed by the Foundation for the National Institutes of Health and funded by the National Institute of Neurological Disorders and Stroke (NINDS) in partnership with the Food and Drug Administration (FDA), National Institute on Aging (NIA), Aligning Science Across Parkinson’s (ASAP) initiative; Celgene Corporation, a subsidiary of Bristol-Myers Squibb Company; GlaxoSmithKline plc (GSK); The Michael J. Fox Foundation for Parkinson’s Research (MJFF); AbbVie Inc.; Pfizer Inc.; Sanofi US Services Inc.; and Verily Life Sciences LLC.
The AMP® PDRD program is a public-private partnership managed by the Foundation for the National Institutes of Health and funded by the National Institute of Neurological Disorders and Stroke (NINDS) in partnership with the Food and Drug Administration (FDA), National Institute on Aging (NIA), AbbVie Inc.; Aligning Science Across Parkinson’s (ASAP) initiative; C2N Diagnostics, LLC; CurePSP; GlaxoSmithKline plc (GSK); Denali Therapeutics Inc.; Laboratory Corporation of America Holdings (Labcorp); The Michael J. Fox Foundation for Parkinson’s Research (MJFF); Sanofi US Services Inc.; and Verily Life Sciences LLC.
ACCELERATING MEDICINES PARTNERSHIP and AMP are registered service marks of the U.S. Department of Health and Human Services.
Competing interests: The authors declare no competing interests.