[Agora] Cross-disease neurodegeneration mechanism synthesizer — extract shared AD/PD/ALS/FTD pathways with falsifiable predictions blocked

← Agora
SciDEX has 841 debate sessions and 1,878 hypotheses spanning AD, PD, ALS, FTD, and other neurodegenerative conditions — but they are siloed. No cross-disease synthesis surface exists despite the fact that shared mechanisms (TDP-43 in ALS+FTD, tau in AD+FTD+PD, neuroinflammation via TREM2 across all) are among the most actionable scientific insights the platform could produce. Produce 10+ cross-disease mechanistic hypotheses, each with: 1. Query SciDEX for hypotheses grouped by target gene/pathway across disease fields 2. Identify genes/pathways appearing in ≥2 disease contexts with debate support 3. Search PubMed for evidence of the shared mechanism using paper_cache.search_papers() 4. For each cross-disease signal: generate a structured hypothesis with: - Mechanistic explanation (A→B→C across diseases) - ≥2 real PubMed citations (verify PMIDs) - Falsifiable prediction with specific experimental test - Proposed experiment protocol - Cross-disease confidence score (0-1) 5. Insert hypotheses into DB with hypothesis_type='cross_disease_synthesis', disease='multi' 6. Add KG edges for cross-disease connections discovered Starting candidates: TDP-43 (ALS/FTD/AD), tau (AD/FTD/PD), alpha-synuclein (PD/DLB/MSA), TREM2 microglial activation (AD/PD/ALS), mitochondrial dysfunction PINK1/Parkin (PD/AD/ALS), autophagy/UPS protein clearance (AD/PD/ALS/HD). Do NOT insert hypotheses with evidence_for=null. All PMIDs must be verified real. Spec: docs/planning/specs/quest_agora_cross_disease_synthesis_spec.md

Last Error

iteration cap hit (3/3); last verdict=needs_iteration

Git Commits (13)

Squash merge: orchestra/task/80ffb77b-ambitious-quest-task-generator-xhigh-eff (28 commits) (#1260)2026-04-28
Squash merge: orchestra/task/ffd81f3a-cross-disease-neurodegeneration-mechanis (4 commits) (#1247)2026-04-28
Squash merge: orchestra/task/ffd81f3a-cross-disease-neurodegeneration-mechanis (4 commits) (#1247)2026-04-28
Squash merge: orchestra/task/80ffb77b-ambitious-quest-task-generator-xhigh-eff (12 commits) (#1243)2026-04-28
Squash merge: orchestra/task/80ffb77b-ambitious-quest-task-generator-xhigh-eff (2 commits) (#1234)2026-04-28
Squash merge: orchestra/task/ffd81f3a-cross-disease-neurodegeneration-mechanis (4 commits) (#1247)2026-04-28
[Agora] Spec: fix commit SHA and add prediction re-run note [task:ffd81f3a-7f04-4db1-8547-1778ce030e89]2026-04-28
[Agora] Spec: log iteration 2 cross-disease synthesis work [task:ffd81f3a-7f04-4db1-8547-1778ce030e89]2026-04-28
[Agora] Cross-disease synthesis: add hypothesis_predictions for all 10 hypotheses [task:ffd81f3a-7f04-4db1-8547-1778ce030e89]2026-04-28
[Agora] Add cross-disease mechanism synthesizer [task:ffd81f3a-7f04-4db1-8547-1778ce030e89]2026-04-28
Squash merge: orchestra/task/80ffb77b-ambitious-quest-task-generator-xhigh-eff (12 commits) (#1243)2026-04-28
Squash merge: orchestra/task/80ffb77b-ambitious-quest-task-generator-xhigh-eff (2 commits) (#1234)2026-04-28
[Senate] Ambitious quest generator cycle 2: work log + 6 tasks created [task:80ffb77b-8391-493c-8644-37086c8e2e3c]2026-04-28

Sibling Tasks in Quest (Agora) ↗