{
  "analysis_version": "gfod2_exclusion_sensitivity_v01",
  "status": "COMPLETE_REPRODUCIBLE_SENSITIVITY_ANALYSIS",
  "target_excluded": "GFOD2",
  "scope": "resource_benchmark_and_current_action_queue_robustness",
  "claim_boundary": "Does not validate or refute the biological importance of GFOD2 in DMD/NMD.",
  "conclusion": "Removing GFOD2 preserves both RMSE conclusions and the mixed response-module cosine interpretation; no replacement top gene or numeric current rank is created.",
  "point_estimates": [
    {
      "scope": "all_2160_targets",
      "excluded_gene": null,
      "metric": "rmse_difference_vs_zero",
      "n_realizations": 20,
      "n_targets": 2160,
      "mean_across_realizations_and_targets": -0.006127467231202905,
      "between_realization_sd": 0.00009155129906355177,
      "delta_vs_all_targets": 0
    },
    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "rmse_difference_vs_zero",
      "n_realizations": 20,
      "n_targets": 2159,
      "mean_across_realizations_and_targets": -0.006146453413307336,
      "between_realization_sd": 0.00009157557578169599,
      "delta_vs_all_targets": -0.000018986182104430843
    },
    {
      "scope": "all_2160_targets",
      "excluded_gene": null,
      "metric": "rmse_difference_vs_train_mean",
      "n_realizations": 20,
      "n_targets": 2160,
      "mean_across_realizations_and_targets": -0.00030185694636412815,
      "between_realization_sd": 0.00009268189696975337,
      "delta_vs_all_targets": 0
    },
    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "rmse_difference_vs_train_mean",
      "n_realizations": 20,
      "n_targets": 2159,
      "mean_across_realizations_and_targets": -0.000303225125261862,
      "between_realization_sd": 0.00009273688355206032,
      "delta_vs_all_targets": -0.0000013681788977338303
    },
    {
      "scope": "all_2160_targets",
      "excluded_gene": null,
      "metric": "raw_cosine_difference_vs_train_mean",
      "n_realizations": 20,
      "n_targets": 2160,
      "mean_across_realizations_and_targets": 0.0008194548403136344,
      "between_realization_sd": 0.0002716244440856091,
      "delta_vs_all_targets": 0
    },
    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "raw_cosine_difference_vs_train_mean",
      "n_realizations": 20,
      "n_targets": 2159,
      "mean_across_realizations_and_targets": 0.0008202300508973099,
      "between_realization_sd": 0.00027169665898010826,
      "delta_vs_all_targets": 7.752105836755568e-7
    },
    {
      "scope": "all_2160_targets",
      "excluded_gene": null,
      "metric": "perturbation_specific_residual_cosine",
      "n_realizations": 20,
      "n_targets": 2160,
      "mean_across_realizations_and_targets": 0.029681311208291813,
      "between_realization_sd": 0.0035069329620371413,
      "delta_vs_all_targets": 0
    },
    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "perturbation_specific_residual_cosine",
      "n_realizations": 20,
      "n_targets": 2159,
      "mean_across_realizations_and_targets": 0.030042497730695363,
      "between_realization_sd": 0.0035057525331770962,
      "delta_vs_all_targets": 0.0003611865224035504
    }
  ],
  "gfod2_target_effects": [
    {
      "gene": "GFOD2",
      "metric": "rmse_difference_vs_zero",
      "n_realizations": 20,
      "mean": 0.03486369993225809,
      "sd": 0.0013961777271953163,
      "minimum": 0.0335083063852357,
      "maximum": 0.0379398889370622
    },
    {
      "gene": "GFOD2",
      "metric": "rmse_difference_vs_train_mean",
      "n_realizations": 20,
      "mean": 0.00265204129384305,
      "sd": 0.001291074499746695,
      "minimum": 0.001791707725127,
      "maximum": 0.0054072843248962
    },
    {
      "gene": "GFOD2",
      "metric": "raw_cosine_difference_vs_train_mean",
      "n_realizations": 20,
      "mean": -0.0008542248098422099,
      "sd": 0.0006369263538171345,
      "minimum": -0.0019414657173989,
      "maximum": 0.0007824649604571
    },
    {
      "gene": "GFOD2",
      "metric": "perturbation_specific_residual_cosine",
      "n_realizations": 20,
      "mean": -0.7501203906609633,
      "sd": 0.018644046596800225,
      "minimum": -0.7716268169598763,
      "maximum": -0.7046534130390264
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  ],
  "corrected_two_stage_uncertainty": [
    {
      "scope": "all_2160_targets",
      "excluded_gene": null,
      "metric": "rmse_difference_vs_zero",
      "n_realizations": 20,
      "n_targets_per_realization": 2160,
      "mean_across_realizations_and_targets": -0.006127467231202905,
      "two_stage_mean_ci95_low": -0.006365679314091502,
      "two_stage_mean_ci95_high": -0.005885222628778012,
      "interval_classification": "favors_model",
      "bootstrap_replicates": 10000,
      "bootstrap_seed": 20260738
    },
    {
      "scope": "all_2160_targets",
      "excluded_gene": null,
      "metric": "rmse_difference_vs_train_mean",
      "n_realizations": 20,
      "n_targets_per_realization": 2160,
      "mean_across_realizations_and_targets": -0.0003018569463641282,
      "two_stage_mean_ci95_low": -0.00037013376402738284,
      "two_stage_mean_ci95_high": -0.0002215073571934488,
      "interval_classification": "favors_model",
      "bootstrap_replicates": 10000,
      "bootstrap_seed": 20260738
    },
    {
      "scope": "all_2160_targets",
      "excluded_gene": null,
      "metric": "raw_cosine_difference_vs_train_mean",
      "n_realizations": 20,
      "n_targets_per_realization": 2160,
      "mean_across_realizations_and_targets": 0.0008194548403136344,
      "two_stage_mean_ci95_low": 0.0006193314932570892,
      "two_stage_mean_ci95_high": 0.0010255203628990203,
      "interval_classification": "favors_model",
      "bootstrap_replicates": 10000,
      "bootstrap_seed": 20260738
    },
    {
      "scope": "all_2160_targets",
      "excluded_gene": null,
      "metric": "perturbation_specific_residual_cosine",
      "n_realizations": 20,
      "n_targets_per_realization": 2160,
      "mean_across_realizations_and_targets": 0.029681311208291813,
      "two_stage_mean_ci95_low": 0.025826149724088254,
      "two_stage_mean_ci95_high": 0.033568139825963086,
      "interval_classification": "favors_model",
      "bootstrap_replicates": 10000,
      "bootstrap_seed": 20260738
    },
    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "rmse_difference_vs_zero",
      "n_realizations": 20,
      "n_targets_per_realization": 2159,
      "mean_across_realizations_and_targets": -0.006146453413307336,
      "two_stage_mean_ci95_low": -0.006388932576062019,
      "two_stage_mean_ci95_high": -0.00590512552392177,
      "interval_classification": "favors_model",
      "bootstrap_replicates": 10000,
      "bootstrap_seed": 20260740
    },
    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "rmse_difference_vs_train_mean",
      "n_realizations": 20,
      "n_targets_per_realization": 2159,
      "mean_across_realizations_and_targets": -0.000303225125261862,
      "two_stage_mean_ci95_low": -0.00037108770882789724,
      "two_stage_mean_ci95_high": -0.0002237123890559875,
      "interval_classification": "favors_model",
      "bootstrap_replicates": 10000,
      "bootstrap_seed": 20260740
    },
    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "raw_cosine_difference_vs_train_mean",
      "n_realizations": 20,
      "n_targets_per_realization": 2159,
      "mean_across_realizations_and_targets": 0.0008202300508973099,
      "two_stage_mean_ci95_low": 0.0006166546419766691,
      "two_stage_mean_ci95_high": 0.001019247096434492,
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      "bootstrap_replicates": 10000,
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    },
    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "perturbation_specific_residual_cosine",
      "n_realizations": 20,
      "n_targets_per_realization": 2159,
      "mean_across_realizations_and_targets": 0.030042497730695363,
      "two_stage_mean_ci95_low": 0.026123534850250114,
      "two_stage_mean_ci95_high": 0.03393109417450347,
      "interval_classification": "favors_model",
      "bootstrap_replicates": 10000,
      "bootstrap_seed": 20260740
    }
  ],
  "response_module_block_uncertainty": [
    {
      "scope": "all_2160_targets",
      "excluded_gene": null,
      "metric": "rmse_difference_vs_zero",
      "n_realizations": 20,
      "n_response_profile_modules": 54,
      "minimum_module_size": 40,
      "maximum_module_size": 40,
      "GFOD2_original_module": 49,
      "GFOD2_module_size_after_scope": 40,
      "equal_module_weight_mean": -0.006127467231202906,
      "target_weight_mean": -0.006127467231202905,
      "module_block_ci95_low": -0.011896320753929492,
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      "minimum_module_size": 40,
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      "GFOD2_original_module": 49,
      "GFOD2_module_size_after_scope": 40,
      "equal_module_weight_mean": -0.00030185694636412815,
      "target_weight_mean": -0.0003018569463641282,
      "module_block_ci95_low": -0.0005489820885375299,
      "module_block_ci95_high": -0.000028345427483069563,
      "interval_classification": "favors_model",
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    {
      "scope": "all_2160_targets",
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      "n_realizations": 20,
      "n_response_profile_modules": 54,
      "minimum_module_size": 40,
      "maximum_module_size": 40,
      "GFOD2_original_module": 49,
      "GFOD2_module_size_after_scope": 40,
      "equal_module_weight_mean": 0.0008194548403136344,
      "target_weight_mean": 0.0008194548403136344,
      "module_block_ci95_low": -0.00003077238781845091,
      "module_block_ci95_high": 0.0017490414938115789,
      "interval_classification": "mixed_crosses_zero",
      "bootstrap_replicates": 10000,
      "bootstrap_seed": 20260739
    },
    {
      "scope": "all_2160_targets",
      "excluded_gene": null,
      "metric": "perturbation_specific_residual_cosine",
      "n_realizations": 20,
      "n_response_profile_modules": 54,
      "minimum_module_size": 40,
      "maximum_module_size": 40,
      "GFOD2_original_module": 49,
      "GFOD2_module_size_after_scope": 40,
      "equal_module_weight_mean": 0.02968131120829181,
      "target_weight_mean": 0.029681311208291813,
      "module_block_ci95_low": -0.009052790145867594,
      "module_block_ci95_high": 0.07031752398827561,
      "interval_classification": "mixed_crosses_zero",
      "bootstrap_replicates": 10000,
      "bootstrap_seed": 20260739
    },
    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "rmse_difference_vs_zero",
      "n_realizations": 20,
      "n_response_profile_modules": 54,
      "minimum_module_size": 39,
      "maximum_module_size": 40,
      "GFOD2_original_module": 49,
      "GFOD2_module_size_after_scope": 39,
      "equal_module_weight_mean": -0.006130843569116817,
      "target_weight_mean": -0.006146453413307336,
      "module_block_ci95_low": -0.01200385419858773,
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      "interval_classification": "favors_model",
      "bootstrap_replicates": 10000,
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    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "rmse_difference_vs_train_mean",
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      "n_response_profile_modules": 54,
      "minimum_module_size": 39,
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      "GFOD2_original_module": 49,
      "GFOD2_module_size_after_scope": 39,
      "equal_module_weight_mean": -0.00030358299624244433,
      "target_weight_mean": -0.000303225125261862,
      "module_block_ci95_low": -0.0005502449919264492,
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      "interval_classification": "favors_model",
      "bootstrap_replicates": 10000,
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    },
    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "raw_cosine_difference_vs_train_mean",
      "n_realizations": 20,
      "n_response_profile_modules": 54,
      "minimum_module_size": 39,
      "maximum_module_size": 40,
      "GFOD2_original_module": 49,
      "GFOD2_module_size_after_scope": 39,
      "equal_module_weight_mean": 0.0008213846767551781,
      "target_weight_mean": 0.0008202300508973099,
      "module_block_ci95_low": -0.000043016561291265144,
      "module_block_ci95_high": 0.0017579744369795953,
      "interval_classification": "mixed_crosses_zero",
      "bootstrap_replicates": 10000,
      "bootstrap_seed": 20260741
    },
    {
      "scope": "leave_GFOD2_out",
      "excluded_gene": "GFOD2",
      "metric": "perturbation_specific_residual_cosine",
      "n_realizations": 20,
      "n_response_profile_modules": 54,
      "minimum_module_size": 39,
      "maximum_module_size": 40,
      "GFOD2_original_module": 49,
      "GFOD2_module_size_after_scope": 39,
      "equal_module_weight_mean": 0.029963260241191822,
      "target_weight_mean": 0.030042497730695363,
      "module_block_ci95_low": -0.008720551295540764,
      "module_block_ci95_high": 0.0701625136702929,
      "interval_classification": "mixed_crosses_zero",
      "bootstrap_replicates": 10000,
      "bootstrap_seed": 20260741
    }
  ],
  "candidate_action_summary": [
    {
      "current_action": "verify_expression",
      "current_display_label": "Verify expression",
      "current_action_order": 0,
      "n_candidates_all_21": 4,
      "n_candidates_leave_GFOD2_out": 4,
      "numeric_current_rank_assigned": "False"
    },
    {
      "current_action": "risk_review",
      "current_display_label": "Risk/context review",
      "current_action_order": 1,
      "n_candidates_all_21": 7,
      "n_candidates_leave_GFOD2_out": 7,
      "numeric_current_rank_assigned": "False"
    },
    {
      "current_action": "muscle_assay",
      "current_display_label": "Muscle-context assay",
      "current_action_order": 2,
      "n_candidates_all_21": 2,
      "n_candidates_leave_GFOD2_out": 2,
      "numeric_current_rank_assigned": "False"
    },
    {
      "current_action": "computational_replication",
      "current_display_label": "Computational replication",
      "current_action_order": 3,
      "n_candidates_all_21": 7,
      "n_candidates_leave_GFOD2_out": 7,
      "numeric_current_rank_assigned": "False"
    },
    {
      "current_action": "hold_pending_external_audit",
      "current_display_label": "Provisional hold · external report not yet audited",
      "current_action_order": 4,
      "n_candidates_all_21": 1,
      "n_candidates_leave_GFOD2_out": 0,
      "numeric_current_rank_assigned": "False"
    }
  ],
  "claim_gates": [
    {
      "gate": "canonical_two_stage_serialized_numeric_match_rmse_difference_vs_zero",
      "status": "PASS",
      "detail": "recomputed=[-0.0063656793140915019,-0.0058852226287780121]; canonical=[-0.0063656793140915002,-0.005885222628778]; absolute_tolerance=1e-15"
    },
    {
      "gate": "canonical_two_stage_serialized_numeric_match_rmse_difference_vs_train_mean",
      "status": "PASS",
      "detail": "recomputed=[-0.00037013376402738284,-0.0002215073571934488]; canonical=[-0.00037013376402730001,-0.00022150735719340001]; absolute_tolerance=1e-15"
    },
    {
      "gate": "canonical_two_stage_serialized_numeric_match_raw_cosine_difference_vs_train_mean",
      "status": "PASS",
      "detail": "recomputed=[0.00061933149325708924,0.0010255203628990203]; canonical=[0.00061933149325700001,0.0010255203628989999]; absolute_tolerance=1e-15"
    },
    {
      "gate": "canonical_two_stage_serialized_numeric_match_perturbation_specific_residual_cosine",
      "status": "PASS",
      "detail": "recomputed=[0.025826149724088254,0.033568139825963086]; canonical=[0.025826149724088199,0.033568139825963003]; absolute_tolerance=1e-15"
    },
    {
      "gate": "canonical_module_serialized_numeric_match_rmse_difference_vs_zero",
      "status": "PASS",
      "detail": "recomputed=[-0.011896320753929492,-0.00028189168959688664]; canonical=[-0.0118963207539294,-0.00028189168959680001]; absolute_tolerance=1e-15"
    },
    {
      "gate": "canonical_module_serialized_numeric_match_rmse_difference_vs_train_mean",
      "status": "PASS",
      "detail": "recomputed=[-0.0005489820885375299,-2.8345427483069563e-05]; canonical=[-0.00054898208853749997,-2.8345427483069563e-05]; absolute_tolerance=1e-15"
    },
    {
      "gate": "canonical_module_serialized_numeric_match_raw_cosine_difference_vs_train_mean",
      "status": "PASS",
      "detail": "recomputed=[-3.0772387818450913e-05,0.0017490414938115789]; canonical=[-3.0772387818450913e-05,0.0017490414938114999]; absolute_tolerance=1e-15"
    },
    {
      "gate": "canonical_module_serialized_numeric_match_perturbation_specific_residual_cosine",
      "status": "PASS",
      "detail": "recomputed=[-0.0090527901458675938,0.070317523988275607]; canonical=[-0.0090527901458675002,0.070317523988275593]; absolute_tolerance=1e-15"
    },
    {
      "gate": "candidate_count_after_exclusion",
      "status": "PASS",
      "detail": "all=21; leave_GFOD2_out=20"
    },
    {
      "gate": "no_replacement_top_gene",
      "status": "PASS",
      "detail": "Remaining candidates retain action-then-gene display; no numeric current rank is assigned."
    },
    {
      "gate": "direction_preserved_two_stage_rmse_difference_vs_zero",
      "status": "PASS",
      "detail": "all=favors_model; leave_GFOD2_out=favors_model; leave-out CI=[-0.006389,-0.005905]"
    },
    {
      "gate": "direction_preserved_two_stage_rmse_difference_vs_train_mean",
      "status": "PASS",
      "detail": "all=favors_model; leave_GFOD2_out=favors_model; leave-out CI=[-0.000371,-0.000224]"
    },
    {
      "gate": "direction_preserved_two_stage_raw_cosine_difference_vs_train_mean",
      "status": "PASS",
      "detail": "all=favors_model; leave_GFOD2_out=favors_model; leave-out CI=[0.000617,0.001019]"
    },
    {
      "gate": "direction_preserved_two_stage_perturbation_specific_residual_cosine",
      "status": "PASS",
      "detail": "all=favors_model; leave_GFOD2_out=favors_model; leave-out CI=[0.026124,0.033931]"
    },
    {
      "gate": "direction_preserved_module_block_rmse_difference_vs_zero",
      "status": "PASS",
      "detail": "all=favors_model; leave_GFOD2_out=favors_model; leave-out CI=[-0.012004,-0.000193]"
    },
    {
      "gate": "direction_preserved_module_block_rmse_difference_vs_train_mean",
      "status": "PASS",
      "detail": "all=favors_model; leave_GFOD2_out=favors_model; leave-out CI=[-0.000550,-0.000032]"
    },
    {
      "gate": "direction_preserved_module_block_raw_cosine_difference_vs_train_mean",
      "status": "PASS",
      "detail": "all=mixed_crosses_zero; leave_GFOD2_out=mixed_crosses_zero; leave-out CI=[-0.000043,0.001758]"
    },
    {
      "gate": "direction_preserved_module_block_perturbation_specific_residual_cosine",
      "status": "PASS",
      "detail": "all=mixed_crosses_zero; leave_GFOD2_out=mixed_crosses_zero; leave-out CI=[-0.008721,0.070163]"
    },
    {
      "gate": "claim_boundary_not_biological_validation",
      "status": "PASS",
      "detail": "This is a benchmark and queue-robustness analysis. It neither validates nor refutes the biological importance of GFOD2 in DMD/NMD."
    },
    {
      "gate": "external_negative_evidence_not_inferred",
      "status": "PASS",
      "detail": "Author-reported cross-project findings remain unaudited until effect estimates, uncertainty, sample definition, code, and provenance are imported."
    }
  ],
  "manifest": {
    "status": "COMPLETE_REPRODUCIBLE_SENSITIVITY_ANALYSIS",
    "analysis_version": "gfod2_exclusion_sensitivity_v01",
    "target_excluded": "GFOD2",
    "claim_boundary": "Resource-benchmark and action-queue robustness only; no biological-null or therapeutic claim.",
    "n_realizations": 20,
    "n_targets_full": 2160,
    "n_targets_after_exclusion": 2159,
    "seeds": {
      "realizations": [
        20260717,
        20260718,
        20260719,
        20260720,
        20260721,
        20260722,
        20260723,
        20260724,
        20260725,
        20260726,
        20260727,
        20260728,
        20260729,
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}