high requested science_discovery

Objective

Continue Jesse Gray synthetic-biology cell-control trajectory jesse-gray-20260525T042012: execute the MERFISH-based ARC-SARE/FOS hybrid enhancer validation challenge, incorporating domain and rigor review feedback (CREB site count, SST subtype breakdown, scran normalization). Artifact graph: landscape=cd0dcb48-b157-4475-a584-da1f2d1643c9, knowledge_gap=6bb44f01-a63a-4758-871c-85684972ceab, hypothesis=06bd01a3-0a80-4c32-94a3-5a6805384b6f, challenge=4275e95a-a5e7-4ccd-8292-d289964f966a. showcase_query_id=cell-control-construct-loop

Instructions

1. Validate that hybrid ARC-SARE/FOS construct design includes ≥3 CREB sites as per domain review revision. 2. Run MERFISH profiling of hybrid vs. monolithic ARC SARE and FOS reporters (sparse optogenetic activation, ≥200 cells/condition). 3. Compute scran log-normalized Spearman ρ for endogenous ARC/FOS correlation (target: ρ ≥ 0.3). 4. Run LNP vs. AAV delivery comparison (target: ρ ≥ 0.5). 5. Report SST-Martinotti vs. SST-NGF subtype breakdown. 6. Update hypothesis confidence score after challenge result.

Roles
domain_reviewer, rigor_reviewer
Next action
execute_merfish_hybrid_enhancer_challenge
Packet kind
science_discovery
Source policy
public-safe
Source run
jesse-gray-20260525T042012

Acceptance criteria

  • domain_reviewer and rigor_reviewer verdicts recorded on hypothesis
  • at least 1 revision applied after review
  • challenge execution attempted or blocked with documented reason
  • hypothesis confidence score updated
  • MERFISH readout covers ≥500 gene panel anchored to ABC Atlas

Inputs

  • cd0dcb48-b157-4475-a584-da1f2d1643c9
  • 6bb44f01-a63a-4758-871c-85684972ceab
  • 06bd01a3-0a80-4c32-94a3-5a6805384b6f
  • 4275e95a-a5e7-4ccd-8292-d289964f966a
  • 620a22d0-5933-49c0-aae2-473502561595
  • c792598c-2c45-4deb-abb5-0142975bfc63
  • a60cb82b-c827-4077-81f5-f715bd5d124a

Context

  • {}

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