{
  "source": "Original study supplementary workbook MOESM15, sheet 3e, compared against a targeted secondary CPM analysis of 24 directly mapped raw-count columns",
  "n_independent_donor_lines": 6,
  "technical_replicates_per_group": 2,
  "dose_ng_ml": 2000,
  "induction_days": 3,
  "shared_genes": 18,
  "genes": {
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      "our_exploratory_CPM_plus_half_fold_change": 0.6570254135795662,
      "our_donor_lines_increased": 0,
      "our_donor_lines_decreased": 6,
      "authors_supplementary_DESeq2": {
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        "foldChange": 0.5562243538227577,
        "pvalue": 1.5526347194717e-05,
        "adjusted_pvalue": 6.19990803420674e-05,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "IL1B": {
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      "our_exploratory_CPM_plus_half_fold_change": 1.0084941670725178,
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      "authors_supplementary_DESeq2": {
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        "adjusted_pvalue": 0.84514187500588,
        "is_spliced": false,
        "status": "Background"
      }
    },
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      "our_exploratory_CPM_plus_half_fold_change": 0.36905644275831806,
      "our_donor_lines_increased": 0,
      "our_donor_lines_decreased": 6,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": -1.56350005981471,
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        "pvalue": 5.78097655386696e-07,
        "adjusted_pvalue": 3.03667239469958e-06,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "CXCL8": {
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      "our_exploratory_CPM_plus_half_fold_change": 2.61316979365296,
      "our_donor_lines_increased": 6,
      "our_donor_lines_decreased": 0,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": 2.31665947252748,
        "foldChange": 4.981773647274364,
        "pvalue": 2.16981853515928e-06,
        "adjusted_pvalue": 1.02010332100354e-05,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "CDKN1A": {
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      "our_exploratory_CPM_plus_half_fold_change": 2.205344587737591,
      "our_donor_lines_increased": 6,
      "our_donor_lines_decreased": 0,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": 0.853646506959842,
        "foldChange": 1.8070626278816002,
        "pvalue": 8.43387924793123e-05,
        "adjusted_pvalue": 0.000292297630509196,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "IL6": {
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      "our_exploratory_CPM_plus_half_fold_change": 0.7660297527510057,
      "our_donor_lines_increased": 2,
      "our_donor_lines_decreased": 4,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": -0.649869276255577,
        "foldChange": 0.637338060751628,
        "pvalue": 0.0819401714914954,
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        "is_spliced": false,
        "status": "Background"
      }
    },
    "SERPINE1": {
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      "our_exploratory_CPM_plus_half_fold_change": 0.5502874840817332,
      "our_donor_lines_increased": 0,
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      "authors_supplementary_DESeq2": {
        "log2FoldChange": -1.10124979874926,
        "foldChange": 0.46611253010548465,
        "pvalue": 8.30745348826696e-05,
        "adjusted_pvalue": 0.000288258627062757,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "MYC": {
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      "our_exploratory_CPM_plus_half_fold_change": 0.8370141119676439,
      "our_donor_lines_increased": 0,
      "our_donor_lines_decreased": 6,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": -0.628388090728647,
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        "is_spliced": false,
        "status": "Background"
      }
    },
    "CDKN2A": {
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      "our_donor_lines_increased": 0,
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      "authors_supplementary_DESeq2": {
        "log2FoldChange": -2.07183231903796,
        "foldChange": 0.23785721304612517,
        "pvalue": 1.66469331091107e-07,
        "adjusted_pvalue": 9.68669632250772e-07,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "MKI67": {
      "our_exploratory_mean_log2_CPM_difference": -0.39859880235243345,
      "our_exploratory_CPM_plus_half_fold_change": 0.7585947002129855,
      "our_donor_lines_increased": 2,
      "our_donor_lines_decreased": 4,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": -0.568834919943044,
        "foldChange": 0.6741610021769846,
        "pvalue": 0.196572168239973,
        "adjusted_pvalue": 0.280415553152455,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "CCND1": {
      "our_exploratory_mean_log2_CPM_difference": 0.03195117115915055,
      "our_exploratory_CPM_plus_half_fold_change": 1.0223939265156803,
      "our_donor_lines_increased": 3,
      "our_donor_lines_decreased": 3,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": -0.479082633773967,
        "foldChange": 0.7174336734143589,
        "pvalue": 0.0324726092224052,
        "adjusted_pvalue": 0.0601218650906548,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "KRAS": {
      "our_exploratory_mean_log2_CPM_difference": -0.17676301529882732,
      "our_exploratory_CPM_plus_half_fold_change": 0.884685746546036,
      "our_donor_lines_increased": 1,
      "our_donor_lines_decreased": 5,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": -0.403490476710922,
        "foldChange": 0.7560269265441676,
        "pvalue": 7.97645236701517e-05,
        "adjusted_pvalue": 0.000277557698117139,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "NFKBIA": {
      "our_exploratory_mean_log2_CPM_difference": 0.3637989850837096,
      "our_exploratory_CPM_plus_half_fold_change": 1.2868099398202553,
      "our_donor_lines_increased": 5,
      "our_donor_lines_decreased": 1,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": 0.013427653970733,
        "foldChange": 1.0093507884753057,
        "pvalue": 0.910207957810081,
        "adjusted_pvalue": 0.938614235690636,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "MAPK3": {
      "our_exploratory_mean_log2_CPM_difference": -0.1558599808514908,
      "our_exploratory_CPM_plus_half_fold_change": 0.8975971617253995,
      "our_donor_lines_increased": 1,
      "our_donor_lines_decreased": 5,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": -0.38360977601213,
        "foldChange": 0.7665172816978587,
        "pvalue": 0.00119068979414499,
        "adjusted_pvalue": 0.00320226095432492,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "TP53": {
      "our_exploratory_mean_log2_CPM_difference": 0.44409233294422457,
      "our_exploratory_CPM_plus_half_fold_change": 1.3604579193619029,
      "our_donor_lines_increased": 5,
      "our_donor_lines_decreased": 1,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": 0.211434086579336,
        "foldChange": 1.1578385418629824,
        "pvalue": 0.061635357986422,
        "adjusted_pvalue": 0.10449343249326,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "COL1A1": {
      "our_exploratory_mean_log2_CPM_difference": -0.975051675429083,
      "our_exploratory_CPM_plus_half_fold_change": 0.5087216239889725,
      "our_donor_lines_increased": 0,
      "our_donor_lines_decreased": 6,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": -1.24556235261066,
        "foldChange": 0.42174347331420275,
        "pvalue": 0.0330519816804749,
        "adjusted_pvalue": 0.0610431975807234,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "SRSF1": {
      "our_exploratory_mean_log2_CPM_difference": -3.8022806630424006,
      "our_exploratory_CPM_plus_half_fold_change": 0.07168024292608366,
      "our_donor_lines_increased": 0,
      "our_donor_lines_decreased": 6,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": -3.81422269575867,
        "foldChange": 0.07108935247597803,
        "pvalue": 1.40315102893881e-59,
        "adjusted_pvalue": 5.45545120051408e-56,
        "is_spliced": false,
        "status": "Background"
      }
    },
    "MAPK1": {
      "our_exploratory_mean_log2_CPM_difference": 0.024932755492553877,
      "our_exploratory_CPM_plus_half_fold_change": 1.0174322681327692,
      "our_donor_lines_increased": 2,
      "our_donor_lines_decreased": 4,
      "authors_supplementary_DESeq2": {
        "log2FoldChange": -0.233596203907522,
        "foldChange": 0.8505121767111593,
        "pvalue": 0.00198298040618948,
        "adjusted_pvalue": 0.00508619757180739,
        "is_spliced": false,
        "status": "Background"
      }
    }
  },
  "interpretation": "This is a methodological cross-check within the same originating study dataset, not independent biological replication. The authors supplementary DESeq2 output strongly corroborates direction and statistical signal for CXCL8 and CDKN1A up, and CDKN2A, SERPINE1, IL1R1, MYC, COL3A1 down. COL1A1 is directionally down but does not pass the reported adjusted-p-value 0.05 threshold (padj ~0.061).",
  "limitations": [
    "Secondary reanalysis of the originating study, not independent biological replication.",
    "Only six donor-derived fibroblast lines, one Dox dose and one 3-day induction schedule are analyzed.",
    "Technical replicates are not treated as independent biological replicates.",
    "Exploratory sign tests have low power at n=6; no p-value is presented as confirmatory evidence.",
    "Selected marker panel only; no full differential-expression, splice-isoform, protein activity, tumor-incidence, organ-toxicity or clinical analysis.",
    "Bulk RNA expression cannot establish human benefit or safety.",
    "No therapeutic use, gene therapy, or self-experimentation is supported.",
    "The authors DESeq2 table is not independent data; it is the originating study analysis.",
    "The small independent secondary donor-level sign test and the paper DESeq2 model have different statistical assumptions and are not interchangeable."
  ]
}