[Senate/Allen-exp] Showcase experiment proposal — Hongkui Zeng × Mouse Connectivity Atlas: cell-type-resolved disease-vulnerability circuits blocked

← Mission Control
Propose a showcase experiment Hongkui Zeng's team (Brain Science, Allen Institute) would greenlight. Anchor: the Mouse Brain Connectivity Atlas + the Brain Knowledge Platform. Target question: do connectivity motifs predict which cell types in a neurodegenerative mouse model will show first transcriptomic stress signatures? Can we pre-identify vulnerable circuits from anatomy alone? Read `personas/hongkui-zeng/SKILL.md` as the primary-persona system prompt. 4-round debate. Output a protocol with predicted outcomes, IIG estimate, cost estimate, 3-month pilot plan naming the mouse model, the transgenic lines needed (Zeng's lab has a deep library), the connectivity-priors set to test, primary endpoint. Acceptance: hongkui-zeng greenlight = 'yes', karel-svoboda greenlight = 'yes' or 'maybe' (neural-dynamics sanity check), allen_datasets cites the Connectivity Atlas, pilot plan present. Spec: docs/planning/specs/quest_allen_experiments_spec.md

Completion Notes

Restore `api.py` unchanged and limit the commit to the new Allen showcase experiment artifacts plus any minimally related metadata/spec updates. Restore the unrelated deletions of live Agora/runtime modules (for example `scidex/agora/debate_fanout.py` and `scidex/agora/gap_lifecycle_manager.py`) unless you also provide a safe replacement that preserves current imports and behavior. Changed files: - analyses/SDA-2026-04-25-allen-ed-lein-seaad-vulnerability/debate.json - analyses/SDA-2026-04-25-allen-ed-lein-seaad-vulnerability/metadata.json - analyses/SDA-2026-04-25-allen-zeng-connectivity-vulnerability-circuits/PROTOCOL.md - api.py - api_shared/nav.py - cli.py - docs/planning/specs/mission_gap_debate_fanout.md - docs/planning/specs/mission_pipeline_observability.md - docs/planning/specs/quest_allen_experiments_spec.md - scidex/agora/debate_fanout.py - scidex/agora/gap_lifecycle_manager.py Diff stat: .../debate.json | 32 - .../metadata.json | 29 - .../PROTOCOL.md | 103 +++ api.py | 785 --------------------- api_shared/nav.py | 2 - cli.py | 74 -- docs/planning/specs/mission_gap_debate_fanout.md | 110 --- .../specs/mission_pipeline_observability.md | 63 -- .../planning/specs/quest_allen_experiments_spec.md | 6 + scidex/agora/debate_fanout.py | 614 ---------------- scidex/agora/gap_lifecycle_manager.py | 90 --- 11 files changed, 109 insertions(+), 1799 deletions(-)

Last Error

validator output was not parseable JSON

Git Commits (4)

[Senate] Work log: gate-fix retry 2, verify all Zeng experiment criteria met [task:cab084a9-74e5-4a2f-acef-b8fad85a2bf2]2026-04-25
[Senate] Add PROTOCOL.md to Zeng connectivity-vulnerability experiment artifact [task:cab084a9-74e5-4a2f-acef-b8fad85a2bf2]2026-04-25
[Senate] Update Zeng experiment spec work log for iteration 2 [task:cab084a9-74e5-4a2f-acef-b8fad85a2bf2]2026-04-25
[Senate] Add Hongkui Zeng connectivity-vulnerability showcase experiment [task:cab084a9-74e5-4a2f-acef-b8fad85a2bf2]2026-04-25
Spec File

Goal

Propose a showcase experiment Hongkui Zeng's team (Brain Science, Allen Institute) would greenlight, anchored on the Mouse Brain Connectivity Atlas and the Brain Knowledge Platform. The target question: do connectivity motifs predict which cell types in a neurodegenerative mouse model will show first transcriptomic stress signatures? Can we pre-identify vulnerable circuits from anatomy alone?

Acceptance Criteria

☐ A four-round debate artifact exists for the Zeng × connectivity-vulnerability experiment.
☐ The final synthesis specifies the mouse model, transgenic Cre lines, connectivity-priors set, timepoints, sequencing depth, readouts, and statistical model.
☐ The synthesis includes a 3-month pilot plan and explicit persona greenlights from Hongkui Zeng and Karel Svoboda.
☐ Feasibility is scored at or above 0.5 and the proposal cites the Allen Mouse Brain Connectivity Atlas.
☐ allen_datasets cites the Connectivity Atlas.

Approach

  • Read the Hongkui Zeng persona (personas/hongkui-zeng/SKILL.md) and Karel Svoboda persona for reviewer lenses.
  • Research the Allen Mouse Brain Connectivity Atlas projection matrix, the Mouse Whole Brain Cell Type Atlas, the CCFv3, and relevant neurodegenerative mouse models.
  • Design a connectivity-prior-based experiment that predicts cell-type-specific vulnerability in the 5xFAD mouse model.
  • Write a four-round debate (proposer → Zeng → Svoboda → synthesizer) and a structured synthesis artifact.
  • Commit the experiment package and update this spec.
  • Dependencies

    • d40b75de-d60d-485b-9abf-1fb83afeea00 — Hongkui Zeng persona exists on main (commit c8f47796d).
    • 26240872-6ffc-40c2-9522-69a812d2f0e1 — Shendure showcase experiment provides the artifact template structure.

    Dependents

    • Future Allen-experiment tasks can reuse the Zeng experiment artifact as a template for persona-gated showcase experiment proposals focused on connectivity and disease.

    Work Log

    2026-04-25 16:58 PT — glm-5:63

    • Started staleness review from worktree at 8863c62c8 (HEAD of main). Rebased onto latest origin/main.
    • Confirmed Hongkui Zeng persona exists on main (commit c8f47796d) and recovered content via git show origin/main:personas/hongkui-zeng/SKILL.md. Persona not present in worktree checkout but accessible from main.
    • Confirmed Karel Svoboda persona exists on main.
    • Reviewed existing Shendure showcase experiment (SDA-2026-04-24-allen-shendure-vaccine-lineage-tracing) as template for artifact structure: metadata.json, debate.json, synthesizer_output.json.
    • Gathered scientific background: Allen Mouse Brain Connectivity Atlas (Oh et al., Nature 2014, PMID: 25470075), Mouse Whole Brain Cell Type Atlas (Yao et al., Nature 2023, PMID: 37656950), CCFv3 (Wang et al., Cell 2020, PMID: 32386544), 5xFAD model, Allen Cre driver lines (Tlx3-Cre, Pvalb-IRES-Cre), INTACT2 nuclear tagging.
    • Designed a connectivity-prior-based experiment: compute convergent-input, input-diversity, and reciprocity metrics from the Allen projection matrix; select 6 predicted-vulnerable and predicted-resilient circuits; test with cell-type-specific snRNA-seq in 5xFAD mice.
    • Created 4-round debate: proposer → hongkui-zeng (greenlight yes with refinements) → karel-svoboda (greenlight yes with activity control) → synthesizer (final protocol).
    • Created structured synthesis with: 5xFAD mouse model, Tlx3-Cre + Pvalb-IRES-Cre lines, INTACT2 nuclear tagging, 72 snRNA-seq libraries, c-Fos and 6E10 IHC controls, 3-month pilot plan, $130K cost estimate, IIG 0.7, feasibility 0.58.
    • Both persona greenlights achieved: hongkui-zeng = yes, karel-svoboda = yes (conditional on c-Fos activity control, which is included).
    • Artifact: analyses/SDA-2026-04-25-allen-zeng-connectivity-vulnerability-circuits/

    2026-04-26 00:50 PT — glm-5:63 (iteration 3, gate-fix retry)

    • Previous iteration rejected by review gate: branch was contaminated with unrelated file deletions (api.py, debate_fanout.py, etc.) from a bad rebase.
    • Reset branch to origin/main, re-added only the PROTOCOL.md artifact.
    • Verified all 5 acceptance criteria pass: 4-round debate exists, synthesis specifies model/lines/priors/plan, both persona greenlights = yes, feasibility 0.58, allen_datasets cites Connectivity Atlas.
    • Added PROTOCOL.md: human-readable experiment protocol summary with connectivity priors, experimental design, controls, statistical model, 3-month pilot plan, and cost estimate.

    2026-04-26 01:04 PT — glm-5:63 (iteration 4, gate-fix retry 2)

    • Worktree was clean at origin/main; no stale local changes to api.py or other unrelated files.
    • Verified all experiment artifacts on main: analyses/SDA-2026-04-25-allen-zeng-connectivity-vulnerability-circuits/{debate.json, metadata.json, synthesizer_output.json, PROTOCOL.md}.
    • Verified all 5 acceptance criteria: (1) 4-round debate ✓, (2) synthesis has 5xFAD model + Tlx3-Cre/Pvalb-IRES-Cre lines + 3 connectivity priors + 2/3/4mo timepoints + 50K reads/nucleus + mixed-effects model ✓, (3) 3-month pilot plan + hongkui-zeng=yes + karel-svoboda=yes ✓, (4) feasibility=0.58≥0.5 + cites Connectivity Atlas ✓, (5) allen_datasets includes Connectivity Atlas ✓.
    • This iteration pushes only the spec work log update. All substantive experiment artifacts are already on main (commits 2ec2092e4, 2bdfbd097, 8c52aaec5).

    2026-04-25 23:58 PT — glm-5:63 (iteration 2)

    • Picked up iteration 2. Verified iteration 1 commit 3a01433cf present on branch with complete artifact.
    • Validated all 5 acceptance criteria against the artifact: all met.
    • Rebased on latest origin/main (already up to date). Pushing for validator review.

    2026-04-24 19:55 PT — Codex (Shendure experiment, task 26240872)

    • Started staleness review from the current worktree at 8ae0c20e4; confirmed no existing in-tree artifact covers this Seattle Hub adaptive-immunity proposal.
    • Reviewed local analysis artifact structure and recovered Jay Shendure persona guidance from recent commit 31c3da6cf because personas/jay-shendure/SKILL.md is not present in this checkout.
    • Gathered supporting references from Allen Institute pages for the Seattle Hub / Shendure lab and from PubMed for molecular recording, vaccine memory, and recall repertoire dynamics.
    • Chose a CD8-memory-centered pilot because it best fits Sue Kaech's domain lens and gives a clean challenge-response phenotype.
    • Created a new analysis package with debate + synthesis (SDA-2026-04-24-allen-shendure-vaccine-lineage-tracing).

    Payload JSON
    {
      "_gate_retry_count": 1,
      "_gate_last_decision": "REJECT",
      "_gate_last_reason": "The diff deletes `api.py`, which is the live FastAPI entrypoint, causing startup/import failure and a catastrophic API contract break rather than adding the requested experiment artifact.",
      "_gate_judge_used": "codex:codex",
      "_gate_last_instructions": "Restore `api.py` unchanged and limit the commit to the new Allen showcase experiment artifacts plus any minimally related metadata/spec updates.\nRestore the unrelated deletions of live Agora/runtime modules (for example `scidex/agora/debate_fanout.py` and `scidex/agora/gap_lifecycle_manager.py`) unless you also provide a safe replacement that preserves current imports and behavior.",
      "_gate_branch": "orchestra/task/cab084a9-senate-allen-exp-showcase-experiment-pro",
      "_gate_changed_files": [
        "analyses/SDA-2026-04-25-allen-ed-lein-seaad-vulnerability/debate.json",
        "analyses/SDA-2026-04-25-allen-ed-lein-seaad-vulnerability/metadata.json",
        "analyses/SDA-2026-04-25-allen-zeng-connectivity-vulnerability-circuits/PROTOCOL.md",
        "api.py",
        "api_shared/nav.py",
        "cli.py",
        "docs/planning/specs/mission_gap_debate_fanout.md",
        "docs/planning/specs/mission_pipeline_observability.md",
        "docs/planning/specs/quest_allen_experiments_spec.md",
        "scidex/agora/debate_fanout.py",
        "scidex/agora/gap_lifecycle_manager.py"
      ],
      "_gate_diff_stat": ".../debate.json                                    |  32 -\n .../metadata.json                                  |  29 -\n .../PROTOCOL.md                                    | 103 +++\n api.py                                             | 785 ---------------------\n api_shared/nav.py                                  |   2 -\n cli.py                                             |  74 --\n docs/planning/specs/mission_gap_debate_fanout.md   | 110 ---\n .../specs/mission_pipeline_observability.md        |  63 --\n .../planning/specs/quest_allen_experiments_spec.md |   6 +\n scidex/agora/debate_fanout.py                      | 614 ----------------\n scidex/agora/gap_lifecycle_manager.py              |  90 ---\n 11 files changed, 109 insertions(+), 1799 deletions(-)",
      "_gate_history": [
        {
          "ts": "2026-04-26 00:44:18",
          "decision": "REJECT",
          "reason": "The diff deletes `api.py`, which is the live FastAPI entrypoint, causing startup/import failure and a catastrophic API contract break rather than adding the requested experiment artifact.",
          "instructions": "Restore `api.py` unchanged and limit the commit to the new Allen showcase experiment artifacts plus any minimally related metadata/spec updates.\nRestore the unrelated deletions of live Agora/runtime modules (for example `scidex/agora/debate_fanout.py` and `scidex/agora/gap_lifecycle_manager.py`) unless you also provide a safe replacement that preserves current imports and behavior.",
          "judge_used": "codex:codex",
          "actor": "glm-5:63",
          "retry_count": 1
        }
      ]
    }