Single-nucleus RNA-seq integration analysis

Exploratory Score: 0.850 Price: $0.50 Alzheimer's disease postmortem human brain tissue - Korean ancestry Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting DACT1, DAAM1, KCNJ3, KLHDC4, SLC10A7, PPP4R2 in postmortem human brain tissue - Korean ancestry. Primary outcome: cell type-specific gene expression patterns

Description

Integration of GWAS results with ancestry-matched Korean single-nucleus RNA sequencing data from postmortem brain tissue to provide cell type-specific functional annotations of identified genetic loci. This analysis aimed to link genetic variants to gene expression patterns in specific brain cell types, particularly focusing on oligodendrocytes where DACT1 was implicated as a key regulatory mediator of pTau217. The integration also included differential gene expression data from the ROSMAP cohort to further validate findings.

TARGET GENE
DACT1, DAAM1, KCNJ3, KLHDC4, SLC10A7, PPP4R2
MODEL SYSTEM
postmortem human brain tissue - Korean ancestry
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
cell type-specific gene regulation, oligodendrocyte function
SOURCE
extracted_from_pmid_41804841
PRIMARY OUTCOME
cell type-specific gene expression patterns

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.850 composite

📖 Wiki Pages

KCNJ3 GenegeneKCNJ3 ProteinproteinRNA Metabolism Dysregulation in 4R-TauopathiesmechanismRNA Therapeutics for Neurodegeneration Investment investmentRNA Metabolism Dysregulation in Alzheimer's DiseasmechanismRNA Metabolism in NeurodegenerationmechanismRNA Binding Fox-1 Homolog 1 (RBFOX1)geneRNA Binding Fox-1 Homolog 2 (RBFOX2)geneRNA Binding Fox-3 Homolog (NeuN) (RBFOX3)geneRNA Therapeutics: Investment Landscape AnalysisinvestmentGWAS Findings HubmechanismGWAS Findings Hub: Alzheimer's and Parkinson's DismechanismRNA G-quadruplexes in NeurodegenerationmechanismRNA Granule Dysfunction in NeurodegenerationmechanismRNA Metabolism Dysfunction in Corticobasal Syndrommechanism

Protocol

Single-nucleus RNA sequencing, integration with GWAS results, cell type annotation, differential expression analysis

Expected Outcomes

Cell type-specific annotation of GWAS loci, identification of regulatory mechanisms in relevant brain cell types

Success Criteria

significant association between genetic variants and cell type-specific gene expression

Related Hypotheses (5)

TREM2-mediated microglial tau clearance enhancement0.800
HSP90-Tau Disaggregation Complex Enhancement0.752
LRP1-Dependent Tau Uptake Disruption0.747
VCP-Mediated Autophagy Enhancement0.713
Extracellular Vesicle Biogenesis Modulation0.635

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