{ "registry_schema": "nmd-vcell-candidate-decision-registry/1.0", "resource_release": "v1.2.0-measured-dmd-evidence", "interface_build": "EA-20260817-57", "evidence_freeze": "2026-08-03", "record_count": 21, "unit_of_meaning": "one candidate hypothesis linked to one current uncertainty and one action that can change the governed decision state", "ordering_policy": "current action order then gene symbol; no numeric rank, winner or composite target score", "action_counts": { "computational_replication": 7, "hold_pending_external_audit": 1, "muscle_assay": 2, "risk_review": 7, "verify_expression": 4 }, "therapeutic_target_claims_authorized": false, "calibrated_dmd_prediction_claims_authorized": false, "records": [ { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "CPEB1", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "CPEB1 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (0.73 TPM).", "research_question": "Is CPEB1 detectably expressed at RNA and protein level in the intended human muscle model?", "practical_use": "Use this candidate to decide whether a perturbation experiment would be technically interpretable.", "current_action": "verify_expression", "current_action_label": "Verify expression", "decision_available_now": "Expression feasibility must be resolved before perturbation resources are committed.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-06", "label": "Expression feasibility is not verified in the intended model" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Measure CPEB1 RNA and, where a validated 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retain the expression gate and resolve assay specificity or state dependence." }, "routes": { "gene": "/resource/gene/CPEB1", "study_card": "/resource/study-card/CPEB1", "planner": "/resource/planner?gene=CPEB1", "compare": "/resource/compare?genes=CPEB1" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "conflicted", "muscle_tpm": 0.731389, "external_screen_state": "not_assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "DNAAF3", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "DNAAF3 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (0.08 TPM).", "research_question": "Is DNAAF3 detectably expressed at RNA and protein level in the intended human 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"planner": "/resource/planner?gene=DNAAF3", "compare": "/resource/compare?genes=DNAAF3" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "consistent_up", "muscle_tpm": 0.0755557, "external_screen_state": "not_assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "EPS8L1", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "EPS8L1 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (0.24 TPM).", "research_question": "Is EPS8L1 detectably expressed at RNA and protein level in the intended human muscle model?", "practical_use": "Use this candidate to decide whether a perturbation experiment would be technically interpretable.", "current_action": "verify_expression", "current_action_label": "Verify expression", "decision_available_now": "Expression feasibility must be resolved before perturbation resources are committed.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-06", "label": "Expression feasibility is not verified in the intended model" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Measure EPS8L1 RNA and, where a validated reagent exists, protein in the intended myoblast or myotube state.", "result_to_decision": { "concordant_or_feasible": "If the predeclared detectability threshold is met in independent biological replicates, move to a bounded perturbation design.", "equivalent_null_or_stop": "If the target stays below the frozen 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"L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "consistent_up", "muscle_tpm": 0.236384, "external_screen_state": "not_assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "ZFP69B", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "ZFP69B remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (0.16 TPM).", "research_question": "Is ZFP69B detectably expressed at RNA and protein level in the intended human muscle model?", "practical_use": "Use this candidate to decide whether a perturbation experiment would be technically interpretable.", "current_action": "verify_expression", "current_action_label": "Verify expression", "decision_available_now": "Expression feasibility must be resolved before perturbation resources are committed.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-06", "label": "Expression feasibility is not verified in the intended model" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Measure ZFP69B RNA and, where a validated reagent exists, protein in the intended myoblast or myotube state.", "result_to_decision": { "concordant_or_feasible": "If the predeclared detectability threshold is met in independent biological replicates, move to a bounded perturbation design.", "equivalent_null_or_stop": "If the target stays below the frozen detectability threshold, stop or redesign the assay; this is a feasibility result, not evidence of no biological role.", "not_evaluable_or_qc_failure": "If RNA and protein or biological replicates disagree, retain the expression gate and resolve assay specificity or state dependence.", "supportive": "If the predeclared detectability threshold is met in independent biological replicates, move to a bounded perturbation design.", "null": "If the target stays below the frozen detectability threshold, stop or redesign the assay; this is a feasibility result, not evidence of no biological role.", "inconclusive_or_qc_failure": "If RNA and protein or biological replicates disagree, retain the expression gate and resolve assay specificity or state dependence." }, "routes": { "gene": "/resource/gene/ZFP69B", "study_card": "/resource/study-card/ZFP69B", "planner": "/resource/planner?gene=ZFP69B", "compare": "/resource/compare?genes=ZFP69B" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "conflicted", "muscle_tpm": 0.155208, "external_screen_state": "not_assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "INTS13", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "INTS13 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (10.99 TPM).", "research_question": "Does INTS13 have a dependency, toxicity or context-specific safety profile that blocks escalation?", "practical_use": "Use this candidate to decide whether a usable perturbation window exists before testing disease relevance.", "current_action": "risk_review", "current_action_label": "Risk/context review", "decision_available_now": "Safety and dependency context require review before a larger perturbation experiment.", "decision_not_available": [ "whether the gene is a proven therapeutic 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"supportive": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "null": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "inconclusive_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation." }, "routes": { "gene": "/resource/gene/INTS13", "study_card": "/resource/study-card/INTS13", "planner": "/resource/planner?gene=INTS13", "compare": "/resource/compare?genes=INTS13" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "consistent_up", "muscle_tpm": 10.9911, "external_screen_state": "not_assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "NAGLU", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "NAGLU remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (8.66 TPM) and an external myogenic screen has been assessed.", "research_question": "Does NAGLU have a dependency, toxicity or context-specific safety profile that blocks escalation?", "practical_use": "Use this candidate to decide whether a usable perturbation window exists before testing disease relevance.", "current_action": "risk_review", "current_action_label": "Risk/context review", "decision_available_now": "Safety and dependency context require review before a larger perturbation experiment.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-08", "label": "Safety and dependency context blocks escalation" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Run a context-matched dose/time and viability review for NAGLU with engagement, toxicity and stop rules declared in advance.", "result_to_decision": { "concordant_or_feasible": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "equivalent_null_or_stop": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "not_evaluable_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation.", "supportive": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "null": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "inconclusive_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation." }, "routes": { "gene": "/resource/gene/NAGLU", "study_card": "/resource/study-card/NAGLU", "planner": "/resource/planner?gene=NAGLU", "compare": "/resource/compare?genes=NAGLU" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L3a_external_context_screen", "evidence_tier": "G4", "prediction_readiness": "R2", "dmd_source_state": "conflicted", "muscle_tpm": 8.66362, "external_screen_state": "assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "RAC3", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "RAC3 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (0.34 TPM).", "research_question": "Does RAC3 have a dependency, toxicity or context-specific safety profile that blocks escalation?", "practical_use": "Use this candidate to decide whether a usable perturbation window exists before testing disease relevance.", "current_action": "risk_review", "current_action_label": "Risk/context review", "decision_available_now": "Safety and dependency context require review before a larger perturbation experiment.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-08", "label": "Safety and dependency context blocks escalation" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Run a context-matched dose/time and viability review for RAC3 with engagement, toxicity and stop rules declared in advance.", "result_to_decision": { "concordant_or_feasible": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "equivalent_null_or_stop": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "not_evaluable_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation.", "supportive": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "null": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "inconclusive_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation." }, "routes": { "gene": "/resource/gene/RAC3", "study_card": "/resource/study-card/RAC3", "planner": "/resource/planner?gene=RAC3", "compare": "/resource/compare?genes=RAC3" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "conflicted", "muscle_tpm": 0.339463, "external_screen_state": "not_assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "RNASEH2C", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "RNASEH2C remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (9.53 TPM) and an external myogenic screen has been assessed.", "research_question": "Does RNASEH2C have a dependency, toxicity or context-specific safety profile that blocks escalation?", "practical_use": "Use this candidate to decide whether a usable perturbation window exists before testing disease relevance.", "current_action": "risk_review", "current_action_label": "Risk/context review", "decision_available_now": "Safety and dependency context require review before a larger perturbation experiment.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-08", "label": "Safety and dependency context blocks escalation" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Run a context-matched dose/time and viability review for RNASEH2C with engagement, toxicity and stop rules declared in advance.", "result_to_decision": { "concordant_or_feasible": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "equivalent_null_or_stop": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "not_evaluable_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation.", "supportive": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "null": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "inconclusive_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation." }, "routes": { "gene": "/resource/gene/RNASEH2C", "study_card": "/resource/study-card/RNASEH2C", "planner": "/resource/planner?gene=RNASEH2C", "compare": "/resource/compare?genes=RNASEH2C" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L3a_external_context_screen", "evidence_tier": "G4", "prediction_readiness": "R2", "dmd_source_state": "consistent_up", "muscle_tpm": 9.52581, "external_screen_state": "assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "RNF8", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "RNF8 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (4.11 TPM).", "research_question": "Does RNF8 have a dependency, toxicity or context-specific safety profile that blocks escalation?", "practical_use": "Use this candidate to decide whether a usable perturbation window exists before testing disease relevance.", "current_action": "risk_review", "current_action_label": "Risk/context review", "decision_available_now": "Safety and dependency context require review before a larger perturbation experiment.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-08", "label": "Safety and dependency context blocks escalation" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Run a context-matched dose/time and viability review for RNF8 with engagement, toxicity and stop rules declared in advance.", "result_to_decision": { "concordant_or_feasible": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "equivalent_null_or_stop": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "not_evaluable_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation.", "supportive": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "null": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "inconclusive_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation." }, "routes": { "gene": "/resource/gene/RNF8", "study_card": "/resource/study-card/RNF8", "planner": "/resource/planner?gene=RNF8", "compare": "/resource/compare?genes=RNF8" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "conflicted", "muscle_tpm": 4.10534, "external_screen_state": "not_assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "WDR4", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "WDR4 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (4.16 TPM) and an external myogenic screen has been assessed.", "research_question": "Does WDR4 have a dependency, toxicity or context-specific safety profile that blocks escalation?", "practical_use": "Use this candidate to decide whether a usable perturbation window exists before testing disease relevance.", "current_action": "risk_review", "current_action_label": "Risk/context review", "decision_available_now": "Safety and dependency context require review before a larger perturbation experiment.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-08", "label": "Safety and dependency context blocks escalation" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Run a context-matched dose/time and viability review for WDR4 with engagement, toxicity and stop rules declared in advance.", "result_to_decision": { "concordant_or_feasible": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "equivalent_null_or_stop": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "not_evaluable_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation.", "supportive": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "null": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "inconclusive_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation." }, "routes": { "gene": "/resource/gene/WDR4", "study_card": "/resource/study-card/WDR4", "planner": "/resource/planner?gene=WDR4", "compare": "/resource/compare?genes=WDR4" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L3a_external_context_screen", "evidence_tier": "G4", "prediction_readiness": "R2", "dmd_source_state": "consistent_up", "muscle_tpm": 4.15911, "external_screen_state": "assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "ZNF236", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "ZNF236 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (2.01 TPM).", "research_question": "Does ZNF236 have a dependency, toxicity or context-specific safety profile that blocks escalation?", "practical_use": "Use this candidate to decide whether a usable perturbation window exists before testing disease relevance.", "current_action": "risk_review", "current_action_label": "Risk/context review", "decision_available_now": "Safety and dependency context require review before a larger perturbation experiment.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-08", "label": "Safety and dependency context blocks escalation" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Run a context-matched dose/time and viability review for ZNF236 with engagement, toxicity and stop rules declared in advance.", "result_to_decision": { "concordant_or_feasible": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "equivalent_null_or_stop": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "not_evaluable_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation.", "supportive": "If a reproducible perturbation window meets engagement and viability gates across biological units, advance to a functional muscle assay.", "null": "If no acceptable window remains after engagement and QC, stop escalation and retain the negative feasibility evidence.", "inconclusive_or_qc_failure": "If the window is donor-, dose- or reagent-specific, classify the result as context dependent and redesign before escalation." }, "routes": { "gene": "/resource/gene/ZNF236", "study_card": "/resource/study-card/ZNF236", "planner": "/resource/planner?gene=ZNF236", "compare": "/resource/compare?genes=ZNF236" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "conflicted", "muscle_tpm": 2.00686, "external_screen_state": "not_assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "MON1A", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "MON1A remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (8.06 TPM) and an external myogenic screen has been assessed.", "research_question": "Does the MON1A response observed outside muscle transfer to a controlled human myogenic system?", "practical_use": "Use this candidate to test context transfer and decide whether a matched DMD/control study is justified.", "current_action": "muscle_assay", "current_action_label": "Muscle-context assay", "decision_available_now": "Eligible for a preregistered human-myogenic feasibility experiment; not established as a therapeutic target.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-02", "label": "Independent muscle-context perturbation is absent" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Perturb MON1A with at least two independent reagents in a declared human myogenic state and freeze one functional primary endpoint.", "result_to_decision": { "concordant_or_feasible": "If engagement and QC pass, both reagents agree, and the primary phenotype replicates beyond one biological unit, advance to matched DMD/control validation.", "equivalent_null_or_stop": "If engagement and QC pass but the primary phenotype is null, record a null muscle-context outcome and stop treating the non-muscle response as transferable.", "not_evaluable_or_qc_failure": "If reagents, donors or batches disagree, classify the result as inconclusive and resolve heterogeneity before any escalation.", "supportive": "If engagement and QC pass, both reagents agree, and the primary phenotype replicates beyond one biological unit, advance to matched DMD/control validation.", "null": "If engagement and QC pass but the primary phenotype is null, record a null muscle-context outcome and stop treating the non-muscle response as transferable.", "inconclusive_or_qc_failure": "If reagents, donors or batches disagree, classify the result as inconclusive and resolve heterogeneity before any escalation." }, "routes": { "gene": "/resource/gene/MON1A", "study_card": "/resource/study-card/MON1A", "planner": "/resource/planner?gene=MON1A", "compare": "/resource/compare?genes=MON1A" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L3a_external_context_screen", "evidence_tier": "G4", "prediction_readiness": "R2", "dmd_source_state": "conflicted", "muscle_tpm": 8.05698, "external_screen_state": "assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "ZNF133", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "ZNF133 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (4.56 TPM) and an external myogenic screen has been assessed.", "research_question": "Does the ZNF133 response observed outside muscle transfer to a controlled human myogenic system?", "practical_use": "Use this candidate to test context transfer and decide whether a matched DMD/control study is justified.", "current_action": "muscle_assay", "current_action_label": "Muscle-context assay", "decision_available_now": "Eligible for a preregistered human-myogenic feasibility experiment; not established as a therapeutic target.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-02", "label": "Independent muscle-context perturbation is absent" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Perturb ZNF133 with at least two independent reagents in a declared human myogenic state and freeze one functional primary endpoint.", "result_to_decision": { "concordant_or_feasible": "If engagement and QC pass, both reagents agree, and the primary phenotype replicates beyond one biological unit, advance to matched DMD/control validation.", "equivalent_null_or_stop": "If engagement and QC pass but the primary phenotype is null, record a null muscle-context outcome and stop treating the non-muscle response as transferable.", "not_evaluable_or_qc_failure": "If reagents, donors or batches disagree, classify the result as inconclusive and resolve heterogeneity before any escalation.", "supportive": "If engagement and QC pass, both reagents agree, and the primary phenotype replicates beyond one biological unit, advance to matched DMD/control validation.", "null": "If engagement and QC pass but the primary phenotype is null, record a null muscle-context outcome and stop treating the non-muscle response as transferable.", "inconclusive_or_qc_failure": "If reagents, donors or batches disagree, classify the result as inconclusive and resolve heterogeneity before any escalation." }, "routes": { "gene": "/resource/gene/ZNF133", "study_card": "/resource/study-card/ZNF133", "planner": "/resource/planner?gene=ZNF133", "compare": "/resource/compare?genes=ZNF133" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L3a_external_context_screen", "evidence_tier": "G4", "prediction_readiness": "R2", "dmd_source_state": "conflicted", "muscle_tpm": 4.55781, "external_screen_state": "assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "ADAM10", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "ADAM10 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (3.12 TPM) and an external myogenic screen has been assessed.", "research_question": "Does the ADAM10 evidence pattern survive an independent dataset and frozen analysis workflow?", "practical_use": "Use this candidate to decide whether the current computational signal is reproducible enough to justify experimental escalation.", "current_action": "computational_replication", "current_action_label": "Computational replication", "decision_available_now": "Experimental escalation remains provisional until the signal is independently reproduced.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-07", "label": "Independent computational replication is absent" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Repeat the ADAM10 analysis in an independent dataset with frozen mapping, contrasts, baselines, null controls and uncertainty reporting.", "result_to_decision": { "concordant_or_feasible": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "equivalent_null_or_stop": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "not_evaluable_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative.", "supportive": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "null": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "inconclusive_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative." }, "routes": { "gene": "/resource/gene/ADAM10", "study_card": "/resource/study-card/ADAM10", "planner": "/resource/planner?gene=ADAM10", "compare": "/resource/compare?genes=ADAM10" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L3a_external_context_screen", "evidence_tier": "G4", "prediction_readiness": "R2", "dmd_source_state": "conflicted", "muscle_tpm": 3.1162, "external_screen_state": "assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "CALR", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "CALR remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (88.63 TPM) and an external myogenic screen has been assessed.", "research_question": "Does the CALR evidence pattern survive an independent dataset and frozen analysis workflow?", "practical_use": "Use this candidate to decide whether the current computational signal is reproducible enough to justify experimental escalation.", "current_action": "computational_replication", "current_action_label": "Computational replication", "decision_available_now": "Experimental escalation remains provisional until the signal is independently reproduced.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-07", "label": "Independent computational replication is absent" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Repeat the CALR analysis in an independent dataset with frozen mapping, contrasts, baselines, null controls and uncertainty reporting.", "result_to_decision": { "concordant_or_feasible": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "equivalent_null_or_stop": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "not_evaluable_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative.", "supportive": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "null": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "inconclusive_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative." }, "routes": { "gene": "/resource/gene/CALR", "study_card": "/resource/study-card/CALR", "planner": "/resource/planner?gene=CALR", "compare": "/resource/compare?genes=CALR" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L3a_external_context_screen", "evidence_tier": "G4", "prediction_readiness": "R2", "dmd_source_state": "conflicted", "muscle_tpm": 88.6307, "external_screen_state": "assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "DDX19B", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "DDX19B remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (7.23 TPM) and an external myogenic screen has been assessed.", "research_question": "Does the DDX19B evidence pattern survive an independent dataset and frozen analysis workflow?", "practical_use": "Use this candidate to decide whether the current computational signal is reproducible enough to justify experimental escalation.", "current_action": "computational_replication", "current_action_label": "Computational replication", "decision_available_now": "Experimental escalation remains provisional until the signal is independently reproduced.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-07", "label": "Independent computational replication is absent" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Repeat the DDX19B analysis in an independent dataset with frozen mapping, contrasts, baselines, null controls and uncertainty reporting.", "result_to_decision": { "concordant_or_feasible": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "equivalent_null_or_stop": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "not_evaluable_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative.", "supportive": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "null": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "inconclusive_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative." }, "routes": { "gene": "/resource/gene/DDX19B", "study_card": "/resource/study-card/DDX19B", "planner": "/resource/planner?gene=DDX19B", "compare": "/resource/compare?genes=DDX19B" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L3a_external_context_screen", "evidence_tier": "G4", "prediction_readiness": "R2", "dmd_source_state": "conflicted", "muscle_tpm": 7.22865, "external_screen_state": "assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "DNM1", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "DNM1 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (1.4 TPM).", "research_question": "Does the DNM1 evidence pattern survive an independent dataset and frozen analysis workflow?", "practical_use": "Use this candidate to decide whether the current computational signal is reproducible enough to justify experimental escalation.", "current_action": "computational_replication", "current_action_label": "Computational replication", "decision_available_now": "Experimental escalation remains provisional until the signal is independently reproduced.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-07", "label": "Independent computational replication is absent" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Repeat the DNM1 analysis in an independent dataset with frozen mapping, contrasts, baselines, null controls and uncertainty reporting.", "result_to_decision": { "concordant_or_feasible": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "equivalent_null_or_stop": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "not_evaluable_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative.", "supportive": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "null": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "inconclusive_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative." }, "routes": { "gene": "/resource/gene/DNM1", "study_card": "/resource/study-card/DNM1", "planner": "/resource/planner?gene=DNM1", "compare": "/resource/compare?genes=DNM1" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "conflicted", "muscle_tpm": 1.39988, "external_screen_state": "not_assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "EHMT2", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "EHMT2 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (6.41 TPM).", "research_question": "Does the EHMT2 evidence pattern survive an independent dataset and frozen analysis workflow?", "practical_use": "Use this candidate to decide whether the current computational signal is reproducible enough to justify experimental escalation.", "current_action": "computational_replication", "current_action_label": "Computational replication", "decision_available_now": "Experimental escalation remains provisional until the signal is independently reproduced.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-07", "label": "Independent computational replication is absent" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Repeat the EHMT2 analysis in an independent dataset with frozen mapping, contrasts, baselines, null controls and uncertainty reporting.", "result_to_decision": { "concordant_or_feasible": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "equivalent_null_or_stop": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "not_evaluable_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative.", "supportive": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "null": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "inconclusive_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative." }, "routes": { "gene": "/resource/gene/EHMT2", "study_card": "/resource/study-card/EHMT2", "planner": "/resource/planner?gene=EHMT2", "compare": "/resource/compare?genes=EHMT2" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "conflicted", "muscle_tpm": 6.40587, "external_screen_state": "not_assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "LMO2", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "LMO2 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (15.24 TPM).", "research_question": "Does the LMO2 evidence pattern survive an independent dataset and frozen analysis workflow?", "practical_use": "Use this candidate to decide whether the current computational signal is reproducible enough to justify experimental escalation.", "current_action": "computational_replication", "current_action_label": "Computational replication", "decision_available_now": "Experimental escalation remains provisional until the signal is independently reproduced.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-07", "label": "Independent computational replication is absent" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Repeat the LMO2 analysis in an independent dataset with frozen mapping, contrasts, baselines, null controls and uncertainty reporting.", "result_to_decision": { "concordant_or_feasible": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "equivalent_null_or_stop": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "not_evaluable_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative.", "supportive": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "null": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "inconclusive_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative." }, "routes": { "gene": "/resource/gene/LMO2", "study_card": "/resource/study-card/LMO2", "planner": "/resource/planner?gene=LMO2", "compare": "/resource/compare?genes=LMO2" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "conflicted", "muscle_tpm": 15.237, "external_screen_state": "not_assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "MPHOSPH6", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "MPHOSPH6 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (4.95 TPM) and an external myogenic screen has been assessed.", "research_question": "Does the MPHOSPH6 evidence pattern survive an independent dataset and frozen analysis workflow?", "practical_use": "Use this candidate to decide whether the current computational signal is reproducible enough to justify experimental escalation.", "current_action": "computational_replication", "current_action_label": "Computational replication", "decision_available_now": "Experimental escalation remains provisional until the signal is independently reproduced.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-07", "label": "Independent computational replication is absent" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Repeat the MPHOSPH6 analysis in an independent dataset with frozen mapping, contrasts, baselines, null controls and uncertainty reporting.", "result_to_decision": { "concordant_or_feasible": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "equivalent_null_or_stop": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "not_evaluable_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative.", "supportive": "If direction and uncertainty reproduce under the frozen plan, retain the candidate and move to its next context-specific gate.", "null": "If the signal does not reproduce despite adequate coverage and QC, retain the negative result and do not escalate from the original analysis alone.", "inconclusive_or_qc_failure": "If coverage, mapping or source design prevents a fair comparison, mark the replication non-evaluable rather than positive or negative." }, "routes": { "gene": "/resource/gene/MPHOSPH6", "study_card": "/resource/study-card/MPHOSPH6", "planner": "/resource/planner?gene=MPHOSPH6", "compare": "/resource/compare?genes=MPHOSPH6" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L3a_external_context_screen", "evidence_tier": "G4", "prediction_readiness": "R2", "dmd_source_state": "consistent_up", "muscle_tpm": 4.94586, "external_screen_state": "assessed" }, { "contract_schema": "nmd-vcell-candidate-research-use/1.0", "gene": "GFOD2", "object_role": "hypothesis_and_experiment_design_object_not_a_therapeutic_target_claim", "why_in_research_set": "GFOD2 remains in the governed set because a traceable same-context perturbation response is available and skeletal-muscle expression is mapped (2.95 TPM).", "research_question": "Can the reported external GFOD2 evidence be reproduced from traceable quantitative data and provenance?", "practical_use": "Use this candidate to decide whether an external report is strong enough to change the governed evidence state.", "current_action": "hold_pending_external_audit", "current_action_label": "Provisional hold ยท external report not yet audited", "decision_available_now": "Keep the current status unchanged until the external result is imported and audited.", "decision_not_available": [ "whether the gene is a proven therapeutic target", "whether perturbation benefits DMD muscle", "whether the intervention is safe or clinically effective", "whether this candidate is superior to another candidate" ], "decision_blocking_gap": { "code": "GAP-09", "label": "External quantitative evidence has not been imported and audited" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "minimum_next_action": "Import the GFOD2 effect estimates, denominators, analysis rules and provenance, then reproduce the reported conclusion.", "result_to_decision": { "concordant_or_feasible": "If the quantitative result and provenance reproduce, reassign the candidate through the normal evidence-transition rules.", "equivalent_null_or_stop": "If the report cannot be reproduced or supported by its source data, keep the hold and retain the failed audit as evidence.", "not_evaluable_or_qc_failure": "If essential files or metadata are unavailable, keep the report unassessed and do not translate absence into a negative biological result.", "supportive": "If the quantitative result and provenance reproduce, reassign the candidate through the normal evidence-transition rules.", "null": "If the report cannot be reproduced or supported by its source data, keep the hold and retain the failed audit as evidence.", "inconclusive_or_qc_failure": "If essential files or metadata are unavailable, keep the report unassessed and do not translate absence into a negative biological result." }, "routes": { "gene": "/resource/gene/GFOD2", "study_card": "/resource/study-card/GFOD2", "planner": "/resource/planner?gene=GFOD2", "compare": "/resource/compare?genes=GFOD2" }, "highest_supported_level": "L2_observed_same_context_perturbation", "highest_assessed_level": "L2_observed_same_context_perturbation", "evidence_tier": "G3", "prediction_readiness": "R1", "dmd_source_state": "conflicted", "muscle_tpm": 2.94732, "external_screen_state": "not_assessed" } ] }