{ "object_id": "SC:v1.0.0-database-resource:EHMT2:1.5-DRAFT", "card_schema": "nmd-vcell-study-card/1.5", "card_version": "1.5", "resource_release": "v1.0.0-database-resource", "evidence_freeze": "2026-07-25", "interface_build": "EA-20260729-15", "gene": "EHMT2", "card_type": "computational_replication", "current_action_code": "computational_replication", "current_action": "Computational replication", "lifecycle": { "state": "DRAFT", "revision": 1, "immutable": false, "registered_at": null, "supersedes": null, "immutable_after_registration": true }, "decision_blocking_gap": { "code": "GAP-07", "label": "Independent computational replication is absent" }, "highest_missing_evidence_layer": "L4_dmd_functional_validation", "secondary_gaps": [ "GAP-02 independent muscle-context perturbation", "GAP-03 DMD-relevant functional validation" ], "frozen_evidence_snapshot": { "snapshot_schema": "nmd-vcell-study-card-frozen-evidence-snapshot/1.0", "source_record": "gene/EHMT2", "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": 101 }, "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": 0.75, "agreeing_sources": 3, "assessed_sources": 4, "coverage_state": "4_of_4_sources", "uncertainty_state": "direction_conflict_retained" }, "context_metrics": { "skeletal_muscle_median_tpm": 6.40587, "depmap_median_gene_effect": -0.2218054354039832, "moderate_dependency_flag": false }, "visual_boundary": "Descriptive frozen evidence snapshot only; no score, rank, cluster, prediction claim or intervention recommendation is generated." }, "unresolved_question": "Does the EHMT2 evidence pattern replicate in an independent dataset under a frozen analysis plan?", "biological_context": "At least one independent dataset with declared tissue/cell state, disease status and gene-mapping coverage.", "perturbation_modality": "No new wet-lab perturbation is nominated; rerun the frozen direction, pathway and robustness analyses.", "comparator_and_controls": [ "Frozen null and simple baselines.", "Leave-one-source-out analysis.", "Negative-control genes or permuted labels.", "Complete unmatched-identifier report." ], "primary_endpoint": "Predeclared gene-level direction or effect estimate in the independent dataset.", "secondary_endpoints": [ "Pathway concordance.", "Leave-one-source-out robustness.", "Coverage and null-result diagnostics." ], "primary_estimand": "Independent-dataset gene effect and uncertainty under the frozen contrast.", "state_transition_design": { "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" ] } }, "perturbation_direction_rationale": { "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." }, "minimally_important_effect": "Required before registration; derive from assay biology or a justified pilot and store the numeric value with units.", "negligible_effect_margin": "Required before interpreting a null result; store a symmetric or asymmetric numeric margin with units.", "suggested_sample_size_range": "One or more independent datasets; donor/sample adequacy must be justified from the source design rather than a generic target count.", "randomisation_unit": "Independent donor/sample/study unit defined by the source dataset.", "blocking_factors": [ "Study/donor.", "Batch.", "Cell state.", "Dataset-specific covariates." ], "statistical_model": "Dataset-appropriate pseudobulk or aggregate model with donor/sample as the inferential unit.", "multiple_testing_family": "Frozen gene and pathway families with declared adjustment method.", "missing_data_rule": "Define exclusions before unblinding; report all missing units and reasons; do not single-impute primary outcomes without a prespecified sensitivity analysis.", "assay_qc_thresholds": [ "Minimum donor/sample coverage.", "Gene detectability.", "Frozen mapping and exclusion thresholds." ], "guide_concordance_rule": "Not applicable unless the independent dataset contains multiple perturbation reagents.", "donor_replication_rule": "A result must persist beyond a single donor/sample and disclose leave-one-unit-out sensitivity.", "estimated_time_band": "1–4 weeks after data access; planning estimate only.", "estimated_cost_band": "Institution- and assay-dependent; obtain a local itemised quote before registration.", "preregistration_status": "draft_requires_direction_rationale_numeric_effect_margin_sample_size_and_qc_thresholds", "inferential_unit": "Independent biological replicate or independently generated perturbation unit; cells within one aggregate are not inferential replicates.", "evidence_import_requirements": [], "planning_fields_not_applicable": [], "stop_rules": [ "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." ], "escalation_rule": "Escalate from L2 to L3b only after independent context-matched perturbation replication; L4 requires replicated DMD-relevant muscle evidence.", "evidence_transition": "Current evidence state → predeclared independent test → governed evidence-level review.", "data_release_plan": "Release the frozen card, protocol identifiers, analysis code, complete denominators and results irrespective of direction; never overwrite the registered card.", "boundary": "This Study Card is an evidence-gated design scaffold, not a protocol, power calculation, safety claim, prediction or therapeutic recommendation.", "stable_url": "study-card/EHMT2", "exports": { "json": "api/v1.1/study-cards/EHMT2.json", "yaml": "downloads/study-cards/EHMT2.yaml", "tsv": "downloads/study-cards/EHMT2.tsv" } }