SciDEX — Task: [Exchange] Enrich top hypotheses #4-#10 with pathw

## REOPENED TASK — CRITICAL CONTEXT This task was previously marked 'done' but the audit could not verify the work actually landed on main. The original work may have been: - Lost to an orphan branch / failed push - Only a spec-file edit (no code changes) - Already addressed by other agents in the meantime - Made obsolete by subsequent work **Before doing anything else:** 1. **Re-evaluate the task in light of CURRENT main state.** Read the spec and the relevant files on origin/main NOW. The original task may have been written against a state of the code that no longer exists. 2. **Verify the task still advances SciDEX's aims.** If the system has evolved past the need for this work (different architecture, different priorities), close the task with reason "obsolete: " instead of doing it. 3. **Check if it's already done.** Run `git log --grep=''` and read the related commits. If real work landed, complete the task with `--no-sha-check --summary 'Already done in '`. 4. **Make sure your changes don't regress recent functionality.** Many agents have been working on this codebase. Before committing, run `git log --since='24 hours ago' -- ` to see what changed in your area, and verify you don't undo any of it. 5. **Stay scoped.** Only do what this specific task asks for. Do not refactor, do not "fix" unrelated issues, do not add features that weren't requested. Scope creep at this point is regression risk. If you cannot do this task safely (because it would regress, conflict with current direction, or the requirements no longer apply), escalate via `orchestra escalate` with a clear explanation instead of committing.

Completion Notes

Auto-completed by supervisor after successful deploy to main

Git Commits (2)

Squash merge: orchestra/task/f9b8996d-enrich-top-hypotheses-4-10-with-pathway (1 commits)2026-04-15

[Exchange] Enrich CYP46A1 hypothesis with pathway diagram and clinical trials [task:f9b8996d-a553-43c4-8419-06400012800a]2026-04-02

Spec File

[Exchange] Enrich top hypotheses #4-#10 with pathway diagrams and clinical trials

Task ID

f9b8996d-a553-43c4-8419-06400012800a

Goal

Add pathway mermaid diagrams and clinical trial JSON data to hypotheses #4-#10 (by composite_score) that are missing this enrichment.

Current State

Hypotheses #1-3 and #5-#10 already have pathway_diagram and clinical_trials populated
Hypothesis #4 (CYP46A1 Overexpression Gene Therapy, h-2600483e) is missing both fields
All other hypotheses in the top 10 are already enriched

Implementation

Created enrich_top_hypotheses.py script with:

- CYP46A1 pathway diagram showing cholesterol metabolism → lipid raft remodeling → Aβ reduction pathway
- 4 relevant clinical trials (AAV-CYP46A1 gene therapy, efavirenz repurposing, 24-OHC biomarker study, pharmacogenomics)

Script has retry logic for DB lock handling

Work Log

2026-04-02 07:05 — Started. Analyzed all top 10 hypotheses. Only #4 (CYP46A1, h-2600483e) missing enrichment.
2026-04-02 07:10 — Created enrichment script. DB currently corrupted (disk I/O error), script committed for later application.
2026-04-15 19:45 PT — Resumed task. Found DB no longer corrupted. Current top 10 had shifted: hypothesis #4 is now hyp-SDA-2026-04-12-20260411-082446-2c1c9e2d-1 (Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Partially Irreversible) with pathway already present but missing clinical trials. The original CYP46A1 hypothesis (h-2600483e) had been enriched via previous work. Added 4 clinical trials relevant to Aβ/cholinergic pathway: NCT06871839 (lecanemab synaptic plasticity), NCT05592678 (donepezil δ dementia), NCT05801380 (AChE inhibitor efficacy), NCT06639282 (siponimod repurposing). Verified all top 10 hypotheses now have both pathway and clinical_trials populated. API returns 200 for hypothesis page.

Payload JSON

{
  "requirements": {
    "coding": 7,
    "reasoning": 7,
    "analysis": 8
  },
  "completion_shas": [
    "b24444e68b676a19b705bd5ac72a527dcde9a65e"
  ],
  "completion_shas_checked_at": "2026-04-16T02:49:15.904777+00:00"
}