{ "schema": "nmd-vcell-research-answer-registry/1.0", "updated": "2026-09-15", "authority_rule": "A Research Answer Object may only assemble versioned evidence, registered model/task state and an existing Study Card. An unregistered query must abstain and must not inherit evidence from a nearby query.", "deployment_state": "LOCAL_CANDIDATE_NOT_PRODUCTION", "research_answer_schema": "/resource/api/v2/research_answer.schema.json", "unregistered_query_policy": "ABSTAIN_NO_REGISTERED_RESEARCH_ANSWER", "record_count": 1, "new_scientific_claim_count": 0, "records": [ { "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" } ], "answer_set_sha256": "3bb7c7c6b73ab36da0ffd8e684a9b1f0da92869a0dc9a3a366895d044e8a2fae" }