{"artifact":{"id":"analysis_proposal-42844dec-3f76-45bd-be13-93bbe311f807","artifact_type":"analysis_proposal","entity_ids":"[\"entities-pnt001\", \"tauopathies\"]","title":"Analysis Proposal: entities-pnt001 ||| tauopathies","quality_score":0.5,"created_by":"analysis_proposal_generator","provenance_chain":"[]","content_hash":"0fd9d7240034b96e13d92611cd87a7b5db43829de4a4237cceeba5674453935c","metadata":{"_origin":{"url":null,"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 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.","datasets":["Allen Institute for Brain Science Human Brain Atlas (AHBA) - gene expression data"," Accelerating Medicines Partnership: Alzheimer's Disease (AMP-AD) proteomics dataset","International Classification of Diseases (ICD) clinical records linked to neuropathology databases","GEO repository: GSE48350 (tauopathy transcriptomics)","NIAGADS: National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site"],"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\"]","_schema_version":1,"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)"],"source_relations":["associated_with"],"analysis_question":"Can we validate the association between PNT001 (putative protein/gene entity) and tauopathies using multimodal neurodegenerative disease datasets?"},"created_at":"2026-04-27T01:42:30.618688-07:00","updated_at":"2026-04-27T01:42:30.618688-07:00","version_number":4,"parent_version_id":null,"version_tag":null,"changelog":null,"is_latest":1,"lifecycle_state":"active","superseded_by":null,"deprecated_at":null,"deprecated_reason":null,"dependencies":null,"market_price":0.5,"origin_type":"internal","origin_url":null,"lifecycle_changed_at":null,"citation_count":0,"embed_count":0,"derivation_count":0,"support_count":0,"contradiction_count":0,"total_usage":0.0,"usage_score":0.5,"usage_computed_at":null,"quality_status":null,"contributors":[],"answers_question_ids":null,"deprecated_reason_detail":null,"deprecated_reason_code":null,"commit_sha":null,"commit_submodule":null,"last_mutated_at":"2026-05-16T14:51:34.657673-07:00","disputed_at":null,"gap_id":null,"mission_id":null,"intrinsic_priority":null,"effective_priority":null,"artifact_id":"9c934952-1fa7-447e-aaa4-063dfb061866","artifact_dir":null,"primary_filename":null,"accessory_filenames":null,"folder_layout_version":1,"migrated_to_folder_at":null,"hypothesis_id":null,"authorship":{"kind":"human","contributors":[{"role":"author","actor_ref":"analysis_proposal_generator"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[{"target_artifact_id":"wiki-entities-pnt001","link_type":"cites","strength":0.5,"evidence":"Proposal cites relevant entity wiki page"},{"target_artifact_id":"wiki-mechanisms-tauopathies","link_type":"cites","strength":0.5,"evidence":"Proposal cites relevant entity wiki page"}],"incoming_links":[],"current_artifact_id":"analysis_proposal-42844dec-3f76-45bd-be13-93bbe311f807","is_canonical":true,"supersede_chain":["analysis_proposal-42844dec-3f76-45bd-be13-93bbe311f807"]}