{"artifact":{"id":"analysis_proposal-10bf823b-be9d-4266-8ab7-0704bf2707bf","artifact_type":"analysis_proposal","entity_ids":"[\"PVALB\", \"neurodegeneration\"]","title":"Analysis Proposal: PVALB -> neurodegeneration [implicated_in]","quality_score":0.5,"created_by":"analysis_proposal_generator","provenance_chain":"[]","content_hash":"da018f9d08a10c26e8f86585a51d6825f7f3f970050bc0214fad5e6a04ab4f85","metadata":{"_origin":{"url":null,"type":"internal","tracked_at":"2026-04-28T06:46:03.250461"},"methods":["Differential gene expression analysis comparing PVALB levels in affected vs unaffected brain regions using linear models","Gene set enrichment analysis testing PVALB in neurodegenerative disease-related modules","Network propagation analysis on protein-protein interaction networks to assess connectivity to known neurodegeneration genes","Causal inference testing using_summary-data-based Mendelian randomization (SMR) with GWAS summary statistics"],"datasets":["GTEx brain tissue RNA-seq expression data","Allen Brain Atlas single-cell RNA-seq datasets","GWAS Catalog neurodegenerative disease loci","ADNI (Alzheimer's Disease Neuroimaging Initiative) proteomics data"],"edge_count":1,"source_entity":"PVALB","target_entity":"neurodegeneration","edge_signature":"[\"PVALB|neurodegeneration|implicated_in\"]","_schema_version":1,"confidence_range":[0.4,0.4],"expected_outputs":["Log2 fold-change and adjusted p-value for PVALB expression in substantia nigra, hippocampus, and motor cortex across ALS, Parkinson's, and Alzheimer's cohorts; significant downregulation would support the relationship","Enrichment odds ratio and FDR for PVALB within neurodegeneration-associated co-expression modules; connectivity would indicate shared regulatory mechanisms","Propagation significance score and z-statistic measuring network proximity from PVALB to established neurodegeneration genes (e.g., SNCA, LRRK2, MAPT); proximity would corroborate functional relationship","SMR beta and p-value testing pleiotropic colocalization; significant results would indicate shared genetic architecture supporting causal implication"],"source_relations":["implicated_in"],"analysis_question":"Can we validate the relationship between PVALB gene expression changes and neurodegeneration phenotypes across multiple independent datasets?"},"created_at":"2026-04-27T23:46:03.250555-07:00","updated_at":"2026-04-27T23:46:03.250555-07:00","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":"4b114a4d-2423-47cb-8e60-c8c195c5b6e2","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":"kg_edge-5f89d4443dab","link_type":"derives_from","strength":0.5,"evidence":"Proposal derives from source low-confidence KG edge"},{"target_artifact_id":"wiki-genes-pvalb","link_type":"cites","strength":0.5,"evidence":"Proposal cites relevant entity wiki page"},{"target_artifact_id":"wiki-neurodegeneration","link_type":"cites","strength":0.5,"evidence":"Proposal cites relevant entity wiki page"}],"incoming_links":[],"current_artifact_id":"analysis_proposal-10bf823b-be9d-4266-8ab7-0704bf2707bf","is_canonical":true,"supersede_chain":["analysis_proposal-10bf823b-be9d-4266-8ab7-0704bf2707bf"]}