{
  "schema": "dia-health-one.reproduction.v2",
  "run": {
    "id": "DHO-NNC2215-FIG3D-20261018T111522Z",
    "created_at_utc": "2026-10-18T11:15:22.463441+00:00",
    "engine": "Python standard library",
    "engine_version": "3.14.4",
    "analysis": "source-data reanalysis; means, sample SD, paired experiment fold changes",
    "input_sha256": "b7d5bddb7c6e5d2e1b3f016e98f3f18c073681654d23b9a314d6a91c4d13ba4f",
    "script_sha256": "ead0d4abfae1edd6a23e1b76c48f1a628aaa141e878f7bfed00732547af4eda5",
    "environment": {
      "platform": "macOS-26.3-arm64-arm-64bit-Mach-O",
      "architecture": "arm64",
      "dependencies": "Python standard library only",
      "accelerator": "CPU",
      "gpu_simulation": false
    },
    "clinical_use": false
  },
  "source": {
    "doi": "10.1038/s41586-024-08042-3",
    "article": "https://www.nature.com/articles/s41586-024-08042-3",
    "source_data": "https://media.springernature.com/original/springer-static/esm/art%3A10.1038%2Fs41586-024-08042-3/MediaObjects/41586_2024_8042_MOESM5_ESM.xlsx",
    "source_data_sha256": "09a9b6aa4103f9d61af7df03886d59f16d6b09f69f2fe768260548061c7dc81d",
    "accessed_utc_date": "2026-10-17",
    "sheet": "Figure 3d",
    "assay": "hIR-A affinity relative to human insulin; 1.5% HSA",
    "replicates": "Three independent experiments; source workbook values, not digitised chart estimates"
  },
  "inputs": [
    {
      "experiment": 1,
      "analyte": "NNC2215",
      "glucose_mmol_L": 0.0,
      "relative_affinity_percent": 0.7985418265541059,
      "source_sheet": "Figure 3d",
      "source_cell": "B5"
    },
    {
      "experiment": 1,
      "analyte": "NNC2215",
      "glucose_mmol_L": 3.0,
      "relative_affinity_percent": 3.094715268628312,
      "source_sheet": "Figure 3d",
      "source_cell": "C5"
    },
    {
      "experiment": 1,
      "analyte": "NNC2215",
      "glucose_mmol_L": 5.0,
      "relative_affinity_percent": 4.555531869537412,
      "source_sheet": "Figure 3d",
      "source_cell": "D5"
    },
    {
      "experiment": 1,
      "analyte": "NNC2215",
      "glucose_mmol_L": 10.0,
      "relative_affinity_percent": 7.712298682284041,
      "source_sheet": "Figure 3d",
      "source_cell": "E5"
    },
    {
      "experiment": 1,
      "analyte": "NNC2215",
      "glucose_mmol_L": 20.0,
      "relative_affinity_percent": 10.15632401705353,
      "source_sheet": "Figure 3d",
      "source_cell": "F5"
    },
    {
      "experiment": 1,
      "analyte": "Insulin degludec",
      "glucose_mmol_L": 0.0,
      "relative_affinity_percent": 0.3567632436139208,
      "source_sheet": "Figure 3d",
      "source_cell": "B6"
    },
    {
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      "glucose_mmol_L": 3.0,
      "relative_affinity_percent": 0.307669917042643,
      "source_sheet": "Figure 3d",
      "source_cell": "C6"
    },
    {
      "experiment": 1,
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      "glucose_mmol_L": 5.0,
      "relative_affinity_percent": 0.3477624084621644,
      "source_sheet": "Figure 3d",
      "source_cell": "D6"
    },
    {
      "experiment": 1,
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      "glucose_mmol_L": 10.0,
      "relative_affinity_percent": 0.3480918552783744,
      "source_sheet": "Figure 3d",
      "source_cell": "E6"
    },
    {
      "experiment": 1,
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      "relative_affinity_percent": 0.37567899071315924,
      "source_sheet": "Figure 3d",
      "source_cell": "F6"
    },
    {
      "experiment": 2,
      "analyte": "NNC2215",
      "glucose_mmol_L": 0.0,
      "relative_affinity_percent": 0.868466898954704,
      "source_sheet": "Figure 3d",
      "source_cell": "B10"
    },
    {
      "experiment": 2,
      "analyte": "NNC2215",
      "glucose_mmol_L": 3.0,
      "relative_affinity_percent": 3.262691760240392,
      "source_sheet": "Figure 3d",
      "source_cell": "C10"
    },
    {
      "experiment": 2,
      "analyte": "NNC2215",
      "glucose_mmol_L": 5.0,
      "relative_affinity_percent": 4.421816479400749,
      "source_sheet": "Figure 3d",
      "source_cell": "D10"
    },
    {
      "experiment": 2,
      "analyte": "NNC2215",
      "glucose_mmol_L": 10.0,
      "relative_affinity_percent": 6.136528685548294,
      "source_sheet": "Figure 3d",
      "source_cell": "E10"
    },
    {
      "experiment": 2,
      "analyte": "NNC2215",
      "glucose_mmol_L": 20.0,
      "relative_affinity_percent": 9.261083743842367,
      "source_sheet": "Figure 3d",
      "source_cell": "F10"
    },
    {
      "experiment": 2,
      "analyte": "Insulin degludec",
      "glucose_mmol_L": 0.0,
      "relative_affinity_percent": 0.3533581428318271,
      "source_sheet": "Figure 3d",
      "source_cell": "B11"
    },
    {
      "experiment": 2,
      "analyte": "Insulin degludec",
      "glucose_mmol_L": 3.0,
      "relative_affinity_percent": 0.36565047855370436,
      "source_sheet": "Figure 3d",
      "source_cell": "C11"
    },
    {
      "experiment": 2,
      "analyte": "Insulin degludec",
      "glucose_mmol_L": 5.0,
      "relative_affinity_percent": 0.33846980827808637,
      "source_sheet": "Figure 3d",
      "source_cell": "D11"
    },
    {
      "experiment": 2,
      "analyte": "Insulin degludec",
      "glucose_mmol_L": 10.0,
      "relative_affinity_percent": 0.37257495590828926,
      "source_sheet": "Figure 3d",
      "source_cell": "E11"
    },
    {
      "experiment": 2,
      "analyte": "Insulin degludec",
      "glucose_mmol_L": 20.0,
      "relative_affinity_percent": 0.32376578645235365,
      "source_sheet": "Figure 3d",
      "source_cell": "F11"
    },
    {
      "experiment": 3,
      "analyte": "NNC2215",
      "glucose_mmol_L": 0.0,
      "relative_affinity_percent": 0.5909916454776607,
      "source_sheet": "Figure 3d",
      "source_cell": "B15"
    },
    {
      "experiment": 3,
      "analyte": "NNC2215",
      "glucose_mmol_L": 3.0,
      "relative_affinity_percent": 2.473867595818815,
      "source_sheet": "Figure 3d",
      "source_cell": "C15"
    },
    {
      "experiment": 3,
      "analyte": "NNC2215",
      "glucose_mmol_L": 5.0,
      "relative_affinity_percent": 3.7750906892382106,
      "source_sheet": "Figure 3d",
      "source_cell": "D15"
    },
    {
      "experiment": 3,
      "analyte": "NNC2215",
      "glucose_mmol_L": 10.0,
      "relative_affinity_percent": 5.771195097037794,
      "source_sheet": "Figure 3d",
      "source_cell": "E15"
    },
    {
      "experiment": 3,
      "analyte": "NNC2215",
      "glucose_mmol_L": 20.0,
      "relative_affinity_percent": 8.293838862559243,
      "source_sheet": "Figure 3d",
      "source_cell": "F15"
    },
    {
      "experiment": 3,
      "analyte": "Insulin degludec",
      "glucose_mmol_L": 0.0,
      "relative_affinity_percent": 0.3744533947065592,
      "source_sheet": "Figure 3d",
      "source_cell": "B16"
    },
    {
      "experiment": 3,
      "analyte": "Insulin degludec",
      "glucose_mmol_L": 3.0,
      "relative_affinity_percent": 0.3655083655083655,
      "source_sheet": "Figure 3d",
      "source_cell": "C16"
    },
    {
      "experiment": 3,
      "analyte": "Insulin degludec",
      "glucose_mmol_L": 5.0,
      "relative_affinity_percent": 0.3860994311155083,
      "source_sheet": "Figure 3d",
      "source_cell": "D16"
    },
    {
      "experiment": 3,
      "analyte": "Insulin degludec",
      "glucose_mmol_L": 10.0,
      "relative_affinity_percent": 0.4037636969985708,
      "source_sheet": "Figure 3d",
      "source_cell": "E16"
    },
    {
      "experiment": 3,
      "analyte": "Insulin degludec",
      "glucose_mmol_L": 20.0,
      "relative_affinity_percent": 0.40202159430277973,
      "source_sheet": "Figure 3d",
      "source_cell": "F16"
    }
  ],
  "series": {
    "NNC2215": [
      {
        "glucose_mmol_L": 0,
        "values": [
          0.7985418265541059,
          0.868466898954704,
          0.5909916454776607
        ],
        "n": 3,
        "mean": 0.7526667903288236,
        "sd": 0.14431395734488256
      },
      {
        "glucose_mmol_L": 3,
        "values": [
          3.094715268628312,
          3.262691760240392,
          2.473867595818815
        ],
        "n": 3,
        "mean": 2.943758208229173,
        "sd": 0.4155140384597274
      },
      {
        "glucose_mmol_L": 5,
        "values": [
          4.555531869537412,
          4.421816479400749,
          3.7750906892382106
        ],
        "n": 3,
        "mean": 4.250813012725457,
        "sd": 0.4173772252865846
      },
      {
        "glucose_mmol_L": 10,
        "values": [
          7.712298682284041,
          6.136528685548294,
          5.771195097037794
        ],
        "n": 3,
        "mean": 6.540007488290043,
        "sd": 1.031536301038599
      },
      {
        "glucose_mmol_L": 20,
        "values": [
          10.15632401705353,
          9.261083743842367,
          8.293838862559243
        ],
        "n": 3,
        "mean": 9.23708220781838,
        "sd": 0.9314745262091364
      }
    ],
    "Insulin_degludec": [
      {
        "glucose_mmol_L": 0,
        "values": [
          0.3567632436139208,
          0.3533581428318271,
          0.3744533947065592
        ],
        "n": 3,
        "mean": 0.36152492705076905,
        "sd": 0.011325088731624274
      },
      {
        "glucose_mmol_L": 3,
        "values": [
          0.307669917042643,
          0.36565047855370436,
          0.3655083655083655
        ],
        "n": 3,
        "mean": 0.34627625370157095,
        "sd": 0.03343414380085539
      },
      {
        "glucose_mmol_L": 5,
        "values": [
          0.3477624084621644,
          0.33846980827808637,
          0.3860994311155083
        ],
        "n": 3,
        "mean": 0.35744388261858634,
        "sd": 0.025247642450135152
      },
      {
        "glucose_mmol_L": 10,
        "values": [
          0.3480918552783744,
          0.37257495590828926,
          0.4037636969985708
        ],
        "n": 3,
        "mean": 0.37481016939507816,
        "sd": 0.027903147217263724
      },
      {
        "glucose_mmol_L": 20,
        "values": [
          0.37567899071315924,
          0.32376578645235365,
          0.40202159430277973
        ],
        "n": 3,
        "mean": 0.36715545715609754,
        "sd": 0.039818096812937576
      }
    ]
  },
  "fold_changes": [
    {
      "from_glucose_mmol_L": 3,
      "to_glucose_mmol_L": 20,
      "replicate_ratios": [
        3.281828257355377,
        2.8384795207132956,
        3.352579934583807
      ],
      "mean_within_experiment_ratio": 3.1576292375508266,
      "sd_within_experiment_ratio": 0.27864647185235664,
      "ratio_of_group_means": 3.1378535716678226,
      "published_reported_fold": 3.2,
      "matches_published_rounding": true
    },
    {
      "from_glucose_mmol_L": 0,
      "to_glucose_mmol_L": 20,
      "replicate_ratios": [
        12.718587404344786,
        10.663715283782382,
        14.033766680163243
      ],
      "mean_within_experiment_ratio": 12.47202312276347,
      "sd_within_experiment_ratio": 1.6985014166246462,
      "ratio_of_group_means": 12.272472130440221,
      "published_reported_fold": 12.5,
      "matches_published_rounding": true
    }
  ],
  "interpretation": {
    "hill_fit": "A separate exploratory shared-slope Hill fit is recorded in data/hill-fit-summary.json. Its experiment-bootstrap EC50 upper tail is censored at the 1000 mmol/L fit ceiling; no reliable midpoint or 6 mmol/L threshold is inferred.",
    "scope": "Reanalysis of published in-vitro data only. No molecular dynamics, binding free-energy, or patient-response model was run."
  }
}
