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Analysis Proposal: entities-pnt001 ||| tauopathies
active
analysis proposal
Created: 2026-04-27T08:42:30
By: analysis_proposal_generator
Quality:
50%
✓ SciDEX
ID: analysis_proposal-42844dec-3f76-45bd-be1
Analysis Proposal
Analysis Question
Can we validate the association between PNT001 (putative protein/gene entity) and tauopathies using multimodal neurodegenerative disease datasets?
Datasets
Allen Institute for Brain Science Human Brain Atlas (AHBA) - gene expression data Accelerating Medicines Partnership: Alzheimer's Disease (AMP-AD) proteomics datasetInternational Classification of Diseases (ICD) clinical records linked to neuropathology databasesGEO repository: GSE48350 (tauopathy transcriptomics)NIAGADS: National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site
Methods
Step 1: Entity resolution for entities-pnt001 — cross-reference UniProt, Entrez Gene, and HGNC databases to confirm canonical gene symbol and protein aliases. Step 2: Extract PNT001 expression profiles from AHBA postmortem brain tissue (dorsolateral prefrontal cortex, hippocampus, entorhinal cortex) and stratify by neuropathological diagnosis (Braak tau stage 0–VI vs controls). Step 3: Perform differential expression analysis comparing tauopathy cases (Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy) against neurologically normal controls using limma with empirical Bayes smoothing. Step 4: Conduct gene set enrichment analysis (GSEA) against Reactome tau protein post-translational modification and microtubule assembly pathways. Step 5: Query protein-protein interaction databases (STRING v12, BioGRID) for direct interactors previously implicated in tau propagation. Step 6: Integrate AMP-AD prefrontal cortex proteomics data to assess whether PNT001 protein abundance correlates with phosphorylated tau (AT8 epitope) levels via Spearman correlation. Step 7: Apply Mendelian randomization using cis-expression quantitative trait loci (cis-eQTLs) from brain tissue to test causal direction between PNT001 expression and tau burden biomarkers.
Expected Outputs
- volcano plot (differential expression: log2 fold change vs -log10 adjusted p-value)
- heatmap (PNT001 expression across brain regions stratified by Braak stage)
- bar chart (GSEA normalized enrichment scores for tau-related pathways)
- scatter plot with regression line (PNT001 protein abundance vs AT8 phosphor-tau levels)
- table (cis-eQTL instruments, MR beta coefficients, 95% CI, p-value for causal assessment)
- network diagram (PPN001 interactome subgraph highlighting tau-connected nodes)
Related Entities
Metadata
| _origin | {'url': None, 'type': 'internal', 'tracked_at': '2026-04-27T08:42:30.618502'} |
| methods | Step 1: Entity resolution for entities-pnt001 — cross-reference UniProt, Entrez Gene, and HGNC databases to confirm canonical gene symbol and protein aliases. Step 2: Extract PNT001 expression profile |
| datasets | ['Allen Institute for Brain Science Human Brain Atlas (AHBA) - gene expression data', " Accelerating Medicines Partnership: Alzheimer's Disease (AMP-AD) proteomics dataset", 'International Classificat |
| edge_ids | ['e28fe388-a865-4cfa-a493-697c13337f6d'] |
| edge_count | 1 |
| cluster_key | entities-pnt001 ||| tauopathies |
| cluster_type | pair |
| edge_signature | ["e28fe388-a865-4cfa-a493-697c13337f6d"] |
| expected_outputs | ['volcano plot (differential expression: log2 fold change vs -log10 adjusted p-value)', 'heatmap (PNT001 expression across brain regions stratified by Braak stage)', 'bar chart (GSEA normalized enrich |
| source_relations | ['associated_with'] |
| analysis_question | Can we validate the association between PNT001 (putative protein/gene entity) and tauopathies using multimodal neurodegenerative disease datasets? |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral