object_id	card_schema	card_version	resource_release	evidence_freeze	interface_build	research_object_trace	gene	card_type	current_action_code	current_action	lifecycle	decision_blocking_gap	highest_missing_evidence_layer	secondary_gaps	frozen_evidence_snapshot	unresolved_question	biological_context	perturbation_modality	comparator_and_controls	primary_endpoint	secondary_endpoints	primary_estimand	state_transition_design	perturbation_direction_rationale	minimally_important_effect	negligible_effect_margin	suggested_sample_size_range	randomisation_unit	blocking_factors	statistical_model	multiple_testing_family	missing_data_rule	assay_qc_thresholds	guide_concordance_rule	donor_replication_rule	estimated_time_band	estimated_cost_band	preregistration_status	inferential_unit	evidence_import_requirements	planning_fields_not_applicable	stop_rules	escalation_rule	evidence_transition	data_release_plan	boundary	stable_url	exports	download_routes
SC:v1.2.0-measured-dmd-evidence:RNF8:1.5-DRAFT	nmd-vcell-study-card/1.5	1.5	v1.2.0-measured-dmd-evidence	2026-08-03	EA-20260817-57	{"trace_schema":"nmd-vcell-research-object-trace/1.0","resource_release":"v1.2.0-measured-dmd-evidence","interface_build":"EA-20260817-57","gene":"RNF8","gene_object_id":"GENE:v1.2.0-measured-dmd-evidence:RNF8","comparison_object_id":"CMP-20260726-FE0FF0F808F4","planner_object_id":"PLN:v1.2.0-measured-dmd-evidence:RNF8:1.0-DRAFT","study_card_object_id":"SC:v1.2.0-measured-dmd-evidence:RNF8:1.5-DRAFT","outcome_registry_object_id":"OUT:v1.2.0-measured-dmd-evidence:RNF8:PENDING","routes":{"gene":"/resource/gene/RNF8","compare":"/resource/comparison/CMP-20260726-FE0FF0F808F4","planner":"/resource/planner?gene=RNF8&pln=PLN%3Av1.2.0-measured-dmd-evidence%3ARNF8%3A1.0-DRAFT","study_card":"/resource/study-card/RNF8","outcome_registry":"/resource/prediction_registry?gene=RNF8&outcome=OUT%3Av1.2.0-measured-dmd-evidence%3ARNF8%3APENDING"},"chain_status":{"gene_record":"RELEASED","comparison_object":"RELEASED","planner_state":"SERVER_RESTORED_DRAFT","study_card":"DRAFT","outcome_registry":"EMPTY_PENDING"},"claim_boundary":"Traceability only; object links do not register a prediction or measured DMD outcome."}	RNF8	risk_context_review	risk_review	Risk/context review	{"state":"DRAFT","revision":1,"immutable":false,"registered_at":null,"supersedes":null,"immutable_after_registration":true}	{"code":"GAP-08","label":"Safety and dependency context blocks escalation"}	L4_dmd_functional_validation	GAP-02 independent muscle-context perturbation | GAP-03 DMD-relevant functional validation | GAP-07 independent replication	{"snapshot_schema":"nmd-vcell-study-card-frozen-evidence-snapshot/1.0","source_record":"gene/RNF8","highest_supported_level":"L2_observed_same_context_perturbation","highest_assessed_level":"L2_observed_same_context_perturbation","observed_hepg2_perturbation":{"assessment_status":"assessed","support_status":"supported","observed_cells":122},"external_context_screen":{"assessment_status":"not_assessed","support_status":null,"hit":null,"effect_size":null,"fdr":null,"interpretation":null},"dmd_prior":{"integrated_prior_direction":"up","source_direction_state":"conflicted","source_agreement_proportion":0.5,"agreeing_sources":2,"assessed_sources":4,"coverage_state":"4_of_4_sources","uncertainty_state":"direction_conflict_retained"},"context_metrics":{"skeletal_muscle_median_tpm":4.10534,"depmap_median_gene_effect":-0.4776308177317093,"moderate_dependency_flag":true},"visual_boundary":"Descriptive frozen evidence snapshot only; no score, rank, cluster, prediction claim or intervention recommendation is generated."}	Does perturbing RNF8 have a context-dependent dependency or toxicity profile that blocks escalation?	Matched disease-relevant and non-disease human myogenic contexts plus a tissue-breadth/dependency audit.	Dose/time perturbation series only after expression feasibility; include at least two reagents where feasible.	Non-targeting and mock controls. | Positive toxicity control. | Matched healthy/DMD or isogenic context. | Dose and time vehicle controls.	Predeclared viability or essentiality endpoint across dose and time.	Target engagement. | Functional muscle phenotype. | Off-target and tissue-breadth context.	Context-by-dose interaction for the primary safety endpoint.	{"scientific_object":"perturbation × cell state × disease context × time × phenotype","mechanism_hypothesis":"Required before registration: state the proposed early molecular mediator, the expected cell-state transition and the downstream functional consequence.","cell_context_fields":{"disease_background":"Required before registration: healthy, DMD or isogenic corrected.","myogenic_state":"Required before registration: proliferating myoblast, early differentiation, fusion or maturing myotube.","donor_or_isogenic_pair":"Required before registration; preserve donor-specific estimates."},"timepoint_plan":[{"window":"6–12 h","role":"early molecular or signalling response","status":"planning_default_requires_assay_calibration"},{"window":"24–48 h","role":"regulatory program and cell-state transition","status":"planning_default_requires_assay_calibration"},{"window":"4–7 d","role":"differentiation and functional phenotype","status":"planning_default_requires_assay_calibration"}],"endpoint_domains":{"target_engagement":["mRNA","protein where validated","perturbation efficiency"],"functional":["fusion","morphology","membrane integrity","calcium","contraction"],"safety":["viability","proliferation","differentiation blockade","global stress"],"replication":["reagent","donor or isogenic pair","future batch"]},"cell_cell_consequence":{"current_status":"not_assessed","future_levels":["conditioned medium","two-cell co-culture","three-dimensional muscle model","spatial perturbation model"]},"response_archetype":{"current_status":"not_assessed","allowed_values":["robust_responder","dmd_specific_responder","donor_variable","state_specific","toxic_responder","null_with_equivalence_margin","discordant","qc_failure","inconclusive"]}}	{"selected_hypothesis":"unresolved_requires_registration","allowed_hypotheses":["activation","inhibition","bidirectional_exploration","direction_not_identifiable"],"required_justification":"State whether the disease-associated direction is hypothesized as causal, compensatory or accompanying, and preserve the opposite-direction alternative. DMD direction and counteralignment never choose an intervention automatically."}	Required before registration; derive from assay biology or a justified pilot and store the numeric value with units.	Required before interpreting a null result; store a symmetric or asymmetric numeric margin with units.	3–6 independent biological replicates per context for a pilot dose/time grid; final n requires interaction-effect power analysis.	Independent culture well/biological replicate.	Donor/isogenic pair. | Plate. | Dose/time batch. | Reagent.	Mixed-effects dose-response model with context interaction and blocked reagent estimates.	Primary safety endpoint across frozen doses/times; functional endpoints are secondary.	Define exclusions before unblinding; report all missing units and reasons; do not single-impute primary outcomes without a prespecified sensitivity analysis.	Numeric viability floor. | Numeric target-engagement floor. | Predeclared off-target exclusion criteria.	Escalation requires directionally compatible safety estimates from two reagents.	A favourable window must not be attributable to one donor/context.	6–12 weeks after model readiness; planning estimate only.	Institution- and assay-dependent; obtain a local itemised quote before registration.	draft_requires_direction_rationale_numeric_effect_margin_sample_size_and_qc_thresholds	Independent biological replicate or independently generated perturbation unit; cells within one aggregate are not inferential replicates.			Stop or classify as infeasible if a required numeric QC threshold fails. | Do not interpret a nonsignificant result as no material effect without a negligible-effect interval. | Do not change canonical candidate status automatically; require governed review.	Escalate from L2 to L3b only after independent context-matched perturbation replication; L4 requires replicated DMD-relevant muscle evidence.	Current evidence state → predeclared independent test → governed evidence-level review.	Release the frozen card, protocol identifiers, analysis code, complete denominators and results irrespective of direction; never overwrite the registered card.	This Study Card is an evidence-gated design scaffold, not a protocol, power calculation, safety claim, prediction or therapeutic recommendation.	study-card/RNF8	{"json":"api/v1.1/study-cards/RNF8.json","yaml":"downloads/study-cards/RNF8.yaml","tsv":"downloads/study-cards/RNF8.tsv"}	{"yaml":"export/study-cards/RNF8.yaml","tsv":"export/study-cards/RNF8.tsv"}