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.
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-da1f2d1643c96bb44f01-a63a-4758-871c-85684972ceab06bd01a3-0a80-4c32-94a3-5a6805384b6f4275e95a-a5e7-4ccd-8292-d289964f966a620a22d0-5933-49c0-aae2-473502561595c792598c-2c45-4deb-abb5-0142975bfc63a60cb82b-c827-4077-81f5-f715bd5d124a
Context
{}