{
  "schema": "dia-health-one.nnc2215-hill-fit.v1",
  "run": {
    "run_id": "DHO-NNC2215-HILL-20261018T053849Z",
    "created_at_utc": "2026-10-18T05:38:49.173072+00:00",
    "script": "research/fit_nnc2215_hill_response.py",
    "script_sha256": "4b1b358ad31d353401dafa2d1b60ca2a860154f9e87a21401a98ce95732a1097",
    "input": "research/data/source-data.csv",
    "input_sha256": "b7d5bddb7c6e5d2e1b3f016e98f3f18c073681654d23b9a314d6a91c4d13ba4f",
    "engine": "SciPy least_squares and deterministic cluster bootstrap",
    "software": {
      "python": "3.12.15",
      "numpy": "2.5.4",
      "scipy": "1.18.1",
      "matplotlib": "3.11.2"
    },
    "bootstrap_seed": 2215,
    "bootstrap_requested": 2000,
    "bootstrap_converged": 2000,
    "bootstrap_failed": 0
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  "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",
    "sheet": "Figure 3d",
    "assay": "hIR-A affinity relative to human insulin; 1.5% HSA",
    "analyte": "NNC2215",
    "experiments": [
      1,
      2,
      3
    ],
    "glucose_mmol_L": [
      0.0,
      3.0,
      5.0,
      10.0,
      20.0
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    "rows": [
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        "experiment": 1,
        "glucose_mmol_L": 0.0,
        "relative_affinity_percent": 0.7985418265541059,
        "source_sheet": "Figure 3d",
        "source_cell": "B5"
      },
      {
        "experiment": 1,
        "glucose_mmol_L": 3.0,
        "relative_affinity_percent": 3.094715268628312,
        "source_sheet": "Figure 3d",
        "source_cell": "C5"
      },
      {
        "experiment": 1,
        "glucose_mmol_L": 5.0,
        "relative_affinity_percent": 4.555531869537412,
        "source_sheet": "Figure 3d",
        "source_cell": "D5"
      },
      {
        "experiment": 1,
        "glucose_mmol_L": 10.0,
        "relative_affinity_percent": 7.712298682284041,
        "source_sheet": "Figure 3d",
        "source_cell": "E5"
      },
      {
        "experiment": 1,
        "glucose_mmol_L": 20.0,
        "relative_affinity_percent": 10.15632401705353,
        "source_sheet": "Figure 3d",
        "source_cell": "F5"
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        "experiment": 2,
        "glucose_mmol_L": 0.0,
        "relative_affinity_percent": 0.868466898954704,
        "source_sheet": "Figure 3d",
        "source_cell": "B10"
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        "experiment": 2,
        "glucose_mmol_L": 3.0,
        "relative_affinity_percent": 3.262691760240392,
        "source_sheet": "Figure 3d",
        "source_cell": "C10"
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        "experiment": 2,
        "glucose_mmol_L": 5.0,
        "relative_affinity_percent": 4.421816479400749,
        "source_sheet": "Figure 3d",
        "source_cell": "D10"
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        "experiment": 2,
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        "relative_affinity_percent": 6.136528685548294,
        "source_sheet": "Figure 3d",
        "source_cell": "E10"
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        "experiment": 2,
        "glucose_mmol_L": 20.0,
        "relative_affinity_percent": 9.261083743842367,
        "source_sheet": "Figure 3d",
        "source_cell": "F10"
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        "experiment": 3,
        "glucose_mmol_L": 0.0,
        "relative_affinity_percent": 0.5909916454776607,
        "source_sheet": "Figure 3d",
        "source_cell": "B15"
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        "experiment": 3,
        "glucose_mmol_L": 3.0,
        "relative_affinity_percent": 2.473867595818815,
        "source_sheet": "Figure 3d",
        "source_cell": "C15"
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        "experiment": 3,
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        "relative_affinity_percent": 3.7750906892382106,
        "source_sheet": "Figure 3d",
        "source_cell": "D15"
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        "experiment": 3,
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        "source_sheet": "Figure 3d",
        "source_cell": "E15"
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        "source_sheet": "Figure 3d",
        "source_cell": "F15"
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    "values_are_source_workbook_values": true,
    "digitized_from_figure": false
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    "upper_response": "T_i is fitted separately for each independent experiment.",
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      "apparent Hill coefficient n"
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      "EC50_mmol_L": [
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        1000.0
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        10.0
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        "fitted_mean": 9.206527079586147,
        "bootstrap_median_mean": 9.20652708195819,
        "bootstrap_lower_2_5_percent": 8.265338421495454,
        "bootstrap_upper_97_5_percent": 10.16353257153257
      },
      {
        "glucose_mmol_L": 20.0,
        "fitted_mean": 9.225048433799957,
        "bootstrap_median_mean": 9.22504843974326,
        "bootstrap_lower_2_5_percent": 8.282719418975985,
        "bootstrap_upper_97_5_percent": 10.177927918325992
      }
    ]
  },
  "interpretation": {
    "status": "exploratory; EC50 weakly identified",
    "summary": "The fitted midpoint varies widely when the three independent experiments are resampled. Some fits hit the 1000 mmol/L EC50 optimization ceiling, so the upper bootstrap tail is censored and no reliable midpoint interval is identified.",
    "limits": [
      "Only three independent experiment clusters and five glucose concentrations are available.",
      "The observed data do not establish a high-glucose response plateau; EC50 and upper response are therefore strongly correlated.",
      "Bootstrap percentile ranges are fragile with three clusters and are not formal inferential confidence intervals.",
      "The apparent Hill coefficient is a descriptive steepness parameter, not a binding-site count or proof of cooperativity.",
      "No 6 mmol/L activation threshold is inferred; the secondary product-design target remains separate.",
      "This fit describes published receptor-affinity data; it is not a molecular simulation, clinical model, or dosing recommendation."
    ]
  }
}