{"artifact":{"id":"experiment-exp-wiki-experiments-c9orf72-phenotype-divergence-als-ftd","artifact_type":"experiment","entity_ids":null,"title":"C9orf72 Phenotype Divergence: ALS vs FTD Mechanism Study","quality_score":0.675,"created_by":"crosslink-v2","provenance_chain":null,"content_hash":null,"metadata":{"source":{"type":"manual","source_name":"wiki","extracted_by":"backfill_v1","extraction_date":"2026-04-16T01:00:16.905218Z"},"summary":"# C9orf72 Phenotype Divergence: ALS vs FTD Mechanism Study\n## Background and Rationale\nThis comprehensive clinical study addresses the enigmatic phenotypic divergence observed in C9orf72 hexanucleotide repeat expansion carriers, who can develop either amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) despite sharing identical genetic mutations. The C9orf72 repeat expansion is the most common genetic cause of both diseases, yet the molecular mechanisms determining phenotypic ex","entities":{"genes":["FTD"],"diseases":["ALS"]},"model_system":"human","_schema_version":1,"experiment_type":"clinical","primary_outcome":"Identification of transcriptomic and proteomic signatures that distinguish between ALS-predominant and FTD-predominant phenotypes in C9orf72 carriers with 80% predictive accuracy using machine learning algorithms.","methodology_notes":"**Phase 1: Patient Recruitment and Phenotyping (Months 1-6)**\n• Recruit 200 C9orf72 expansion carriers (100 ALS, 100 FTD) through neurology clinics\n• Perform comprehensive neurological assessments using ALS Functional Rating Scale-Revised (ALSFRS-R) and Frontotemporal Dementia Rating Scale (FRS)\n• Collect detailed family history and conduct cognitive testing (Montreal Cognitive Assessment, Addenbrooke's Cognitive Examination)\n• Obtain informed consent for biosampling and genetic analysis\n• Recruit 100 age-matched healthy controls\n\n**Phase 2: Biospecimen Collection and Processing (Months 2-8)**\n• Collect CSF (15mL), plasma (20mL), and serum (10mL) from all participants\n• Extract peripheral blood mononuclear cells (PBMCs) and establish lymphoblastoid cell lines\n• Perform immediate processing and aliquoting at -80°C storage\n• Generate induced pluripotent stem cells (iPSCs) from 50 representative patients (25 ALS, 25 FTD)\n• Differentiate iPSCs into motor neurons and cortical neurons using ","replication_status":"replicated","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.905224","needs_review":true,"extraction_notes":"Backfilled from wiki source (no PMID available)","extraction_confidence":0.4}},"created_at":"2026-04-02T10:01:41.825940-07:00","updated_at":"2026-04-16T01:00:16-07:00","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":"2026-04-02T10:01:41.825940-07:00","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":"ok","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":"39f84558-27cb-40bf-aa47-dfbcdf5e13e4","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":"crosslink-v2"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[{"target_artifact_id":"wiki-technologies-pet-imaging","link_type":"related","strength":0.63,"evidence":"Reverse: 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