{"artifact":{"id":"analysis_proposal-87376ad7-12e1-4fcb-9bf9-bdde40b11d2c","artifact_type":"analysis_proposal","entity_ids":"[\"entities-pnt001\", \"neurofibrillary-tangles\"]","title":"Analysis Proposal: entities-pnt001 ||| neurofibrillary-tangles","quality_score":0.5,"created_by":"analysis_proposal_generator","provenance_chain":"[]","content_hash":"199e1e81f475a173828cb887bd353932c43a83a017db096dd19554b9cdfc1182","metadata":{"_origin":{"url":null,"type":"internal","tracked_at":"2026-04-27T08:43:13.416105"},"methods":"Step 1: Extract expression values of entities-pnt001 from each dataset and map them to brain region and Braak stage.\nStep 2: Perform differential expression analysis (t‑test/Wilcoxon) between NFT‑high (Braak V–VI) and NFT‑low (Braak 0–II) groups.\nStep 3: Compute correlation of entities-pnt001 expression with established NFT markers (e.g., AT8 density, total tau, phosphorylated tau).\nStep 4: Conduct gene‑set enrichment (GO, KEGG) and overlay protein‑protein interaction networks (STRING, BioGRID) to situate entities-pnt001 among known NFT regulators.\nStep 5: Apply Mendelian Randomization (TwoSampleMR) using eQTLs of entities-pnt001 to test a causal effect on NFT burden (quantified by Braak stage or CSF p‑tau levels).\nStep 6: Build a multivariate predictive model (elastic‑net regression) linking entities-pnt001 expression, co‑variates (age, sex, APOE genotype) to NFT severity; evaluate via 10‑fold cross‑validation.","datasets":["Allen Institute for Brain Science Human Brain Atlas (AHBA) – regional transcriptomic data across prefrontal cortex and hippocampus","Mayo Clinic Brain Bank RNA-seq dataset (MayoRNAseq) – temporal cortex samples from AD and control subjects","Religious Orders and Memory and Aging Project (ROSMAP) – longitudinal clinical and RNA‑seq data","Banner Sun Health Research Institute (Banner) – proteomic profiles of Braak‑staged neurofibrillary tangle pathology","Gene Expression Omnibus (GEO) – ArrayExpress dataset for NFT‑enriched vs NFT‑poor brain regions (e.g., GSE124439)"],"edge_ids":["0cb41e0c-a626-4012-a6e3-9677cf4dedde"],"edge_count":1,"cluster_key":"entities-pnt001 ||| neurofibrillary-tangles","cluster_type":"pair","edge_signature":"[\"0cb41e0c-a626-4012-a6e3-9677cf4dedde\"]","_schema_version":1,"expected_outputs":["Figure 1 – Bar plot of entities-pnt001 expression across NFT severity stages with significance bars","Figure 2 – Scatter plot with regression line of entities-pnt001 expression vs AT8 density, including Spearman correlation","Figure 3 – Protein‑protein interaction network diagram highlighting entities-pnt001 and its direct partners, colored by differential expression","Table 1 – Differential expression summary (log2FC, p‑value, FDR) for entities-pnt001 in each cohort","Table 2 – Mendelian randomization results (beta, SE, p‑value) for the causal link between entities-pnt001 eQTLs and NFT burden","Table 3 – Elastic‑net model coefficients and performance metrics (AUC, RMSE) for NFT severity prediction","Model – Multivariate regression (or risk‑score) linking entities-pnt001 expression to neurofibrillary‑tangle load"],"source_relations":["involved_in"],"analysis_question":"Can we validate the involvement of entities-pnt001 in neurofibrillary-tangles using human postmortem brain transcriptomic and proteomic datasets?"},"created_at":"2026-04-27T01:43:13.416225-07:00","updated_at":"2026-04-27T01:43:13.416225-07:00","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":"f4ea71dd-fbc9-47d7-ace0-b9dc35e4ce61","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"}],"incoming_links":[],"current_artifact_id":"analysis_proposal-87376ad7-12e1-4fcb-9bf9-bdde40b11d2c","is_canonical":true,"supersede_chain":["analysis_proposal-87376ad7-12e1-4fcb-9bf9-bdde40b11d2c"]}