---
{
  "answer_id": "ANSWER:Q2:DMD:PROLIFERATING_MYOBLAST:CRISPRI:ZNF133:48H:FUSION_AND_MOLECULAR_RESPONSE:V1",
  "version": "1.0.0",
  "question": {
    "question_schema": "nmd-vcell-research-question/2.0",
    "query_version": "2",
    "question_id": "Q2:DMD:PROLIFERATING_MYOBLAST:CRISPRI:ZNF133:48H:FUSION_AND_MOLECULAR_RESPONSE:SINGLE",
    "disease": "DMD",
    "cell_state": "PROLIFERATING_MYOBLAST",
    "perturbation": "CRISPRI",
    "target": "ZNF133",
    "targets": [
      "ZNF133"
    ],
    "time": "48H",
    "endpoint": "FUSION_AND_MOLECULAR_RESPONSE",
    "study_mode": "SINGLE_TARGET"
  },
  "eligibility": {
    "decision": "ABSTAIN",
    "prediction_permitted": false,
    "reason_codes": [
      "NO_DMD_CANDIDATE_CONDITIONED_OUTCOME",
      "NO_CALIBRATED_DMD_MODEL",
      "MUSCLE_CONTEXT_TRANSFER_UNRESOLVED"
    ],
    "summary": "The question is scientifically actionable but not eligible for a DMD perturbation prediction. The platform can return bounded evidence and a truth-generating experiment design."
  },
  "evidence": [
    {
      "object_id": "GENE:ZNF133:CURRENT",
      "role": "TARGET_CONTEXT",
      "state": "OBSERVED_SAME_CONTEXT_PERTURBATION_OUTSIDE_DMD_OUTCOME",
      "public_path": "/resource/gene/ZNF133"
    },
    {
      "object_id": "REGISTRY:CANDIDATE_DECISIONS:CURRENT",
      "role": "GOVERNS_ACTION",
      "state": "EXPERIMENT_ELIGIBLE_NOT_THERAPEUTIC_TARGET",
      "public_path": "/resource/api/v1.1/candidate_decision_registry.json"
    },
    {
      "object_id": "CLAIM:DMD:CANDIDATE_OUTCOME_BOUNDARY:V1",
      "role": "LIMITS",
      "state": "MISSING_0_OF_21",
      "public_path": "/resource/api/v2/claim_registry.json"
    }
  ],
  "domain_match": [
    {
      "axis": "gene",
      "query_value": "ZNF133",
      "state": "MATCHED_GOVERNED_CANDIDATE",
      "evidence": "Candidate registry and Gene Evidence object"
    },
    {
      "axis": "cell_state",
      "query_value": "PROLIFERATING_MYOBLAST",
      "state": "PARTIAL_CONTEXT_ONLY",
      "evidence": "Human myogenic context exists; matched perturbation truth is absent"
    },
    {
      "axis": "disease",
      "query_value": "DMD",
      "state": "CONTEXT_OBSERVED_OUTCOME_MISSING",
      "evidence": "DMD context exists; candidate-conditioned outcome is 0/21"
    },
    {
      "axis": "perturbation",
      "query_value": "CRISPRI",
      "state": "SOURCE_CONTEXT_ONLY",
      "evidence": "Perturbation evidence does not close muscle/DMD transfer"
    },
    {
      "axis": "time",
      "query_value": "48H",
      "state": "NOT_MATCHED",
      "evidence": "No registered DMD candidate-conditioned 48 h outcome"
    },
    {
      "axis": "endpoint",
      "query_value": "FUSION_AND_MOLECULAR_RESPONSE",
      "state": "NOT_MATCHED",
      "evidence": "No matched DMD fusion plus transcriptomic outcome"
    }
  ],
  "model": {
    "execution_state": "NO_ELIGIBLE_DMD_MODELRUN",
    "eligible_model_run_ids": [],
    "reference_model_run_ids": [
      "MRUN-RIDGE-SAFE-2.3-G0-REPEATED-FOLD",
      "MRUN-TRANSFER-DIAGNOSTIC-1.0-G1"
    ],
    "boundary": "Reference runs answer same-context or transfer-diagnostic tasks. They are not calibrated for this DMD question and are not executed by this answer."
  },
  "baselines": [
    {
      "baseline": "zero_change",
      "state": "REQUIRED_NOT_RUN_FOR_QUERY"
    },
    {
      "baseline": "train_mean",
      "state": "REQUIRED_NOT_RUN_FOR_QUERY"
    },
    {
      "baseline": "ridge",
      "state": "REFERENCE_ONLY_NOT_DMD_ELIGIBLE"
    },
    {
      "baseline": "nearest_neighbour",
      "state": "REGISTERED_FOR_RELEVANT_OOD_TASKS_NOT_RUN_FOR_QUERY"
    }
  ],
  "ood_status": [
    {
      "axis": "gene",
      "state": "BOUNDARY_UNTESTED"
    },
    {
      "axis": "cell_state",
      "state": "OUTSIDE_VALIDATED_PREDICTION_DOMAIN"
    },
    {
      "axis": "disease",
      "state": "OUTSIDE_VALIDATED_PREDICTION_DOMAIN"
    },
    {
      "axis": "donor",
      "state": "NOT_TESTED"
    },
    {
      "axis": "laboratory",
      "state": "NOT_TESTED"
    },
    {
      "axis": "time",
      "state": "NOT_TESTED"
    }
  ],
  "uncertainty": {
    "epistemic": {
      "state": "HIGH",
      "reason": "No calibrated disease-matched predictive model."
    },
    "data": {
      "state": "HIGH",
      "reason": "No candidate-conditioned DMD perturbation outcome."
    },
    "domain": {
      "state": "HIGH",
      "reason": "Muscle, disease, donor, laboratory and time transfer remain unvalidated."
    },
    "quantified": false
  },
  "missing_truth": [
    "Independent human myogenic ZNF133 perturbation response",
    "Matched DMD/control or isogenic-corrected functional outcome",
    "Target engagement and viability under the selected perturbation",
    "Donor-resolved replication",
    "Frozen 48 h molecular endpoint and functional fusion endpoint"
  ],
  "next_experiment": {
    "study_card_id": "SC:v1.2.0-measured-dmd-evidence:ZNF133:1.5-DRAFT",
    "study_card_path": "/resource/study-card/ZNF133",
    "design_state": "DRAFT_REQUIRES_REGISTRATION_FIELDS",
    "context": "Declared human myogenic state with healthy/DMD or isogenic-corrected background",
    "perturbation": "CRISPRi with at least two independent reagents where feasible",
    "primary_endpoint": "One predeclared functional endpoint, with fusion as the query-selected endpoint",
    "secondary_endpoints": [
      "target engagement",
      "viability/toxicity",
      "directional transcriptomic response"
    ],
    "planning_sample_size": "3–6 independent biological replicates per condition and reagent; final powered n remains open",
    "decision_rule": "Advance only if engagement and QC pass, reagents agree, and the phenotype replicates beyond one biological unit. Retain null, discordant and QC-failed results."
  },
  "expected_information_gain": {
    "state": "HIGH_QUALITATIVE_NOT_QUANTIFIED",
    "reason": "The experiment directly addresses the muscle-context transfer gap and can move the object to a null, supportive, discordant or QC-failure outcome state.",
    "numeric_value": null,
    "boundary": "A qualitative priority is not a probability, effect size, therapeutic score or formal value-of-information calculation."
  },
  "claim_ceiling": {
    "level": "EVIDENCE_AND_EXPERIMENT_DESIGN_ONLY",
    "claim_id": "CLAIM:DMD:CANDIDATE_OUTCOME_BOUNDARY:V1",
    "statement": "ZNF133 is eligible for a bounded human-myogenic feasibility experiment. The current evidence does not support a DMD perturbation-response, efficacy, therapeutic-ranking or clinical claim."
  },
  "does_not_imply": [
    "that ZNF133 perturbation benefits DMD muscle",
    "that any model can predict this DMD response",
    "that the qualitative information-gain label is a computed VOI",
    "that the draft Study Card is registered or powered"
  ],
  "citation_metadata": {
    "title": "NMD-VCell Research Answer Object for DMD / ZNF133 / CRISPRi",
    "resource_release": "v1.2.0-measured-dmd-evidence",
    "evidence_freeze": "2026-08-03",
    "doi_state": "PENDING_NO_IDENTIFIER",
    "canonical_path": "/resource/question/"
  },
  "generated_by": [
    "PROCESS:RESEARCH_ANSWER_BUILD:V201"
  ],
  "is_new_scientific_claim": false,
  "research_answer_sha256": "5f3a8032becd59203d545af781bf5ac28e0d2a9b36716ce6e6e3ef1c7e4b80c4"
}