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  "generated": "2026-08-02",
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    "accession": "GSE293514",
    "doi": "10.1038/s41467-025-67583-x",
    "article_url": "https://www.nature.com/articles/s41467-025-67583-x",
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      "individually_validated": false,
      "assessment_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1",
      "supports_dmd_prediction": false,
      "claim_boundary": "healthy-human-myoblast context only; absence of a fusion hit is endpoint-specific and is not evidence of no DMD effect"
    },
    {
      "gene": "NAGLU",
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      "claim_boundary": "healthy-human-myoblast context only; absence of a fusion hit is endpoint-specific and is not evidence of no DMD effect"
    },
    {
      "gene": "RAC3",
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      "fusion_screen_lfc": null,
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      "assessment_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY",
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      "claim_boundary": "healthy-human-myoblast context only; absence of a fusion hit is endpoint-specific and is not evidence of no DMD effect"
    },
    {
      "gene": "RNASEH2C",
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      "fusion_screen_lfc": 0.18037,
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      "assessment_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1",
      "supports_dmd_prediction": false,
      "claim_boundary": "healthy-human-myoblast context only; absence of a fusion hit is endpoint-specific and is not evidence of no DMD effect"
    },
    {
      "gene": "RNF8",
      "in_myo_crispr_library": false,
      "fusion_screen_assessed": false,
      "fusion_screen_lfc": null,
      "fusion_screen_fdr": null,
      "fusion_hit_fdr_lt_0_1": false,
      "individually_validated": false,
      "assessment_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY",
      "supports_dmd_prediction": false,
      "claim_boundary": "healthy-human-myoblast context only; absence of a fusion hit is endpoint-specific and is not evidence of no DMD effect"
    },
    {
      "gene": "WDR4",
      "in_myo_crispr_library": true,
      "fusion_screen_assessed": true,
      "fusion_screen_lfc": -0.010262,
      "fusion_screen_fdr": 0.999999,
      "fusion_hit_fdr_lt_0_1": false,
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      "assessment_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1",
      "supports_dmd_prediction": false,
      "claim_boundary": "healthy-human-myoblast context only; absence of a fusion hit is endpoint-specific and is not evidence of no DMD effect"
    },
    {
      "gene": "ZFP69B",
      "in_myo_crispr_library": false,
      "fusion_screen_assessed": false,
      "fusion_screen_lfc": null,
      "fusion_screen_fdr": null,
      "fusion_hit_fdr_lt_0_1": false,
      "individually_validated": false,
      "assessment_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY",
      "supports_dmd_prediction": false,
      "claim_boundary": "healthy-human-myoblast context only; absence of a fusion hit is endpoint-specific and is not evidence of no DMD effect"
    },
    {
      "gene": "ZNF133",
      "in_myo_crispr_library": true,
      "fusion_screen_assessed": true,
      "fusion_screen_lfc": -0.003533,
      "fusion_screen_fdr": 0.999999,
      "fusion_hit_fdr_lt_0_1": false,
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      "assessment_state": "ASSESSED_NO_FUSION_HIT_AT_FDR_0_1",
      "supports_dmd_prediction": false,
      "claim_boundary": "healthy-human-myoblast context only; absence of a fusion hit is endpoint-specific and is not evidence of no DMD effect"
    },
    {
      "gene": "ZNF236",
      "in_myo_crispr_library": false,
      "fusion_screen_assessed": false,
      "fusion_screen_lfc": null,
      "fusion_screen_fdr": null,
      "fusion_hit_fdr_lt_0_1": false,
      "individually_validated": false,
      "assessment_state": "NOT_INCLUDED_IN_MYOCRISPR_LIBRARY",
      "supports_dmd_prediction": false,
      "claim_boundary": "healthy-human-myoblast context only; absence of a fusion hit is endpoint-specific and is not evidence of no DMD effect"
    }
  ],
  "pathway_signatures": [
    {
      "signature_id": "GSE293514_SEVEN_DONOR_UP_REFERENCE",
      "direction": "up",
      "gene_rows": 150,
      "donor_lines": 7,
      "consensus_core_7_of_7": 72,
      "top_consensus_genes": [
        {
          "gene": "MYOG",
          "core_donors": 7,
          "median_log2_fold_change": 7.895447480133204
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        {
          "gene": "ACTA1",
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          "median_log2_fold_change": 7.856049602665251
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        {
          "gene": "ERBB3",
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        {
          "gene": "ACTN2",
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          "gene": "SRL",
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          "median_log2_fold_change": 7.548890981918265
        },
        {
          "gene": "UNC45B",
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          "median_log2_fold_change": 7.546149035830735
        },
        {
          "gene": "APOBEC2",
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          "median_log2_fold_change": 7.460489329453156
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        {
          "gene": "CDKN1C",
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          "median_log2_fold_change": 7.4497890797790305
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        {
          "gene": "MRLN",
          "core_donors": 7,
          "median_log2_fold_change": 7.297735360478887
        },
        {
          "gene": "MYH3",
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          "median_log2_fold_change": 7.208969623331632
        },
        {
          "gene": "MYMK",
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          "median_log2_fold_change": 7.193538187849098
        },
        {
          "gene": "MYL4",
          "core_donors": 7,
          "median_log2_fold_change": 7.160115227295369
        }
      ],
      "header_columns": 30,
      "evidence_state": "observed_unperturbed_reference_not_perturbation_delta"
    },
    {
      "signature_id": "GSE293514_SEVEN_DONOR_DOWN_REFERENCE",
      "direction": "down",
      "gene_rows": 137,
      "donor_lines": 7,
      "consensus_core_7_of_7": 56,
      "top_consensus_genes": [
        {
          "gene": "RRM2",
          "core_donors": 7,
          "median_log2_fold_change": -6.709083642092842
        },
        {
          "gene": "BIRC5",
          "core_donors": 7,
          "median_log2_fold_change": -6.05908754575008
        },
        {
          "gene": "CENPF",
          "core_donors": 7,
          "median_log2_fold_change": -5.860276089639976
        },
        {
          "gene": "UBE2C",
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          "median_log2_fold_change": -5.746158861654773
        },
        {
          "gene": "LMNB1",
          "core_donors": 7,
          "median_log2_fold_change": -5.160449912567839
        },
        {
          "gene": "ZWINT",
          "core_donors": 7,
          "median_log2_fold_change": -4.066891434867713
        },
        {
          "gene": "HMGA1",
          "core_donors": 7,
          "median_log2_fold_change": -3.532833331846263
        },
        {
          "gene": "CKS2",
          "core_donors": 7,
          "median_log2_fold_change": -3.449134275941942
        },
        {
          "gene": "SMC4",
          "core_donors": 7,
          "median_log2_fold_change": -3.2831493354575954
        },
        {
          "gene": "VIM",
          "core_donors": 7,
          "median_log2_fold_change": -3.1400727276474396
        },
        {
          "gene": "CKS1B",
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          "median_log2_fold_change": -3.095812884854839
        },
        {
          "gene": "ID3",
          "core_donors": 7,
          "median_log2_fold_change": -3.07341774294185
        }
      ],
      "header_columns": 30,
      "evidence_state": "observed_unperturbed_reference_not_perturbation_delta"
    },
    {
      "signature_id": "GSE293514_CROPSEQ_MYOCYTE_SIGNATURE",
      "direction": "myocyte_over_myoblast",
      "gene_rows": 142,
      "top_genes": [
        {
          "gene": "CHRNG",
          "log2_fold_change_myocyte_vs_myoblast": 4.9009814,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "ARPP21",
          "log2_fold_change_myocyte_vs_myoblast": 4.8895254,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "ACTA1",
          "log2_fold_change_myocyte_vs_myoblast": 4.7680745,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "TNNI1",
          "log2_fold_change_myocyte_vs_myoblast": 4.7631254,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "CACNA1S",
          "log2_fold_change_myocyte_vs_myoblast": 4.750926,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "MYBPH",
          "log2_fold_change_myocyte_vs_myoblast": 4.7252913,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "CASQ2",
          "log2_fold_change_myocyte_vs_myoblast": 4.662538,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "LDB3",
          "log2_fold_change_myocyte_vs_myoblast": 4.6623983,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "ENSG00000289950",
          "log2_fold_change_myocyte_vs_myoblast": 4.646098,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "MIR1-1HG",
          "log2_fold_change_myocyte_vs_myoblast": 4.6418896,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "RYR1",
          "log2_fold_change_myocyte_vs_myoblast": 4.585076,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "REEP1",
          "log2_fold_change_myocyte_vs_myoblast": 4.557833,
          "adjusted_p_value": 0.0
        }
      ],
      "evidence_state": "observed_signature_definition_not_candidate_delta"
    },
    {
      "signature_id": "GSE293514_CROPSEQ_MYOBLAST_SIGNATURE",
      "direction": "myoblast_over_myocyte",
      "gene_rows": 253,
      "top_genes": [
        {
          "gene": "MT2A",
          "log2_fold_change_myocyte_vs_myoblast": -6.53197,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "SERPINE1",
          "log2_fold_change_myocyte_vs_myoblast": -6.0203853,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "NPTX2",
          "log2_fold_change_myocyte_vs_myoblast": -5.890263,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "MKI67",
          "log2_fold_change_myocyte_vs_myoblast": -5.815296,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "TOP2A",
          "log2_fold_change_myocyte_vs_myoblast": -5.5340753,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "HMGA2",
          "log2_fold_change_myocyte_vs_myoblast": -5.383269,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "CENPF",
          "log2_fold_change_myocyte_vs_myoblast": -5.3296504,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "NT5E",
          "log2_fold_change_myocyte_vs_myoblast": -5.2090616,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "ANPEP",
          "log2_fold_change_myocyte_vs_myoblast": -5.143213,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "SRGN",
          "log2_fold_change_myocyte_vs_myoblast": -5.1321006,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "DIAPH3",
          "log2_fold_change_myocyte_vs_myoblast": -5.098152,
          "adjusted_p_value": 0.0
        },
        {
          "gene": "CCBE1",
          "log2_fold_change_myocyte_vs_myoblast": -4.973643,
          "adjusted_p_value": 0.0
        }
      ],
      "evidence_state": "observed_signature_definition_not_candidate_delta"
    }
  ],
  "quality_gates": [
    {
      "gate": "official_source_sha256",
      "status": "PASS",
      "detail": "9/9 official supplementary workbooks match frozen SHA-256 values"
    },
    {
      "gate": "published_screen_cardinality",
      "status": "PASS",
      "detail": "6,896 library genes; 7,197 screen rows; 250 hits at FDR < 0.1"
    },
    {
      "gate": "individual_validation_identity",
      "status": "PASS",
      "detail": "125 unique published individually validated hit genes"
    },
    {
      "gate": "myogenesis_signature_cardinality",
      "status": "PASS",
      "detail": "395 genes: 142 myocyte and 253 myoblast markers"
    },
    {
      "gate": "candidate_context_audit",
      "status": "PASS",
      "detail": "9/21 assessed; 0/21 fusion hits; 12/21 not in the library"
    },
    {
      "gate": "candidate_level_transcriptomic_pathway_delta",
      "status": "LOCKED",
      "detail": "The public CROP-seq matrix has 62,711 columns versus a 62,710-row recoverable public gene order; exact author column identity is unresolved"
    },
    {
      "gate": "dmd_transfer",
      "status": "LOCKED",
      "detail": "No matched DMD perturbation outcome is present in GSE293514"
    }
  ],
  "matrix_identity_block": {
    "analysis_eligible": false,
    "matrix_columns": 62711,
    "recoverable_public_gene_order_rows": 62710,
    "missing_author_object": "ordered all_genes.csv or hash-frozen author gene_info",
    "consequence": "Do not attach gene symbols to the public CROP-seq matrix and do not emit candidate-level pathway deltas from it"
  },
  "claim_boundary": "This is an observed healthy-human-myoblast functional perturbation network with a published named-module subset and qualitative grouped CROP-seq state edges. It is not a DMD perturbation network, not a candidate-level expression response atlas, and not a trained virtual-cell predictor.",
  "next_unlock": "Resolve exact GSE293514 expression-column identity for retrospective candidate-level transcriptomic analysis, then generate preregistered matched DMD/control perturbations for disease transfer.",
  "generated_by": "scripts/build_human_myoblast_perturbation_network_stage_b0.py"
}
