agingclockbench 0.1.0__py3-none-any.whl

agingclockbench/cli.py

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+"""Command-line interface for AgingClockBench."""
+
+import sys
+from pathlib import Path
+
+import click
+
+from agingclockbench.config import VERSION
+
+_ALL_CLOCKS = ["PhenoAge", "KDM", "DunedinPACEProxy"]
+
+
+def _load_clocks(names: tuple[str]) -> dict:
+    from agingclockbench import PhenoAge, KDM, DunedinPACEProxy
+    registry = {"PhenoAge": PhenoAge, "KDM": KDM, "DunedinPACEProxy": DunedinPACEProxy}
+    if "all" in names:
+        return {k: v() for k, v in registry.items()}
+    unknown = [n for n in names if n not in registry]
+    if unknown:
+        raise click.BadParameter(
+            f"Unknown clock(s): {unknown}. Choose from {_ALL_CLOCKS} or 'all'."
+        )
+    return {n: registry[n]() for n in names}
+
+
+@click.group()
+@click.version_option(version=VERSION, prog_name="agingclockbench")
+def cli():
+    """AgingClockBench — benchmark biological aging clocks on your data.
+
+    \b
+    Quick start:
+        agingclockbench benchmark --data bundled --clocks all
+    """
+
+
+@cli.command()
+@click.option("--data", required=True,
+              help="Path to input CSV, or 'bundled' to use the NHANES 1999-2000 sample.")
+@click.option("--clocks", multiple=True, default=["PhenoAge"], show_default=True,
+              help="Clocks to run. Repeat for multiple, or pass 'all'. "
+                   f"Choices: {_ALL_CLOCKS}")
+@click.option("--mortality-col", default="mortstat", show_default=True,
+              help="Column for vital status (1=deceased, 0=censored).")
+@click.option("--followup-col", default="permth_exm", show_default=True,
+              help="Column for follow-up time in months.")
+@click.option("--output", default="./results", show_default=True,
+              help="Directory for output files.")
+@click.option("--report", is_flag=True, default=False,
+              help="Generate an interactive HTML report (requires plotly).")
+@click.option("--verbose", is_flag=True, default=False,
+              help="Print detailed progress.")
+def benchmark(data, clocks, mortality_col, followup_col, output, report, verbose):
+    """Run a benchmark comparison of aging clocks on your data.
+
+    \b
+    Examples:
+        agingclockbench benchmark --data bundled --clocks all
+        agingclockbench benchmark --data my_data.csv --clocks PhenoAge KDM --report
+        agingclockbench benchmark --data my_data.csv --clocks all \\
+            --mortality-col vital_status --followup-col followup_months
+    """
+    import pandas as pd
+    from agingclockbench import BenchmarkSuite
+    from agingclockbench.datasets import load_nhanes_sample
+
+    # --- Load data ---
+    if data == "bundled":
+        df = load_nhanes_sample()
+        click.echo(f"Loaded bundled NHANES 1999-2000 sample: {len(df)} participants.")
+    else:
+        try:
+            df = pd.read_csv(data)
+        except Exception as e:
+            raise click.ClickException(f"Could not read {data}: {e}")
+        click.echo(f"Loaded {len(df):,} rows from {data}.")
+
+    # --- Run clocks ---
+    selected = _load_clocks(clocks)
+    results = {}
+    for name, clock in selected.items():
+        try:
+            result = clock.transform(df)
+            results[name] = result
+            click.echo(
+                f"  {name}: {result.output_rows}/{result.input_rows} rows "
+                f"(mean BA = {result.biological_ages.mean():.1f} yr, "
+                f"mean accel = {result.accel.mean():.1f} yr)"
+            )
+        except Exception as e:
+            click.echo(f"  {name}: FAILED — {e}", err=True)
+
+    if not results:
+        raise click.ClickException("No clocks produced results. Exiting.")
+
+    # --- Benchmark ---
+    suite = BenchmarkSuite(mortality_col=mortality_col, followup_col=followup_col)
+    bench_report = suite.run(df, results)
+
+    # --- Output ---
+    out_dir = Path(output)
+    out_dir.mkdir(parents=True, exist_ok=True)
+
+    summary = bench_report.to_dataframe()
+    csv_path = out_dir / "comparison_table.csv"
+    summary.to_csv(csv_path, index=False)
+
+    click.echo(f"\n{'='*60}")
+    click.echo("BENCHMARK RESULTS")
+    click.echo("="*60)
+    click.echo(summary.to_string(index=False))
+    click.echo(f"\nComparison table saved to: {csv_path}")
+
+    if report:
+        html_path = out_dir / "benchmark_report.html"
+        try:
+            bench_report.to_html(str(html_path))
+            click.echo(f"Interactive report saved to: {html_path}")
+        except ImportError:
+            click.echo("plotly not installed — skipping HTML report. Run: pip install plotly",
+                       err=True)
+
+
+@cli.group()
+def datasets():
+    """Manage bundled reference datasets."""
+
+
+@datasets.command("list")
+def datasets_list():
+    """List available bundled datasets."""
+    click.echo("Available bundled datasets:")
+    click.echo("  nhanes_sample  — NHANES 1999-2000 (N=4,086, mortality-linked)")
+    click.echo("                   Columns: age, sex, all 9 PhenoAge biomarkers,")
+    click.echo("                            mortstat, permth_exm")
+
+
+@datasets.command("info")
+def datasets_info():
+    """Print summary statistics for the bundled NHANES sample."""
+    from agingclockbench.datasets import load_nhanes_sample
+    df = load_nhanes_sample()
+    click.echo(f"NHANES 1999-2000 sample — {len(df):,} participants")
+    click.echo(f"  Age: {df.age.min():.0f}–{df.age.max():.0f} yr  "
+               f"(mean {df.age.mean():.1f}, SD {df.age.std():.1f})")
+    click.echo(f"  Deaths: {df.mortstat.sum():,} ({df.mortstat.mean()*100:.1f}%)")
+    click.echo(f"  Median follow-up: {df.permth_exm.median()/12:.1f} yr")
+
+
+@cli.command()
+def version():
+    """Print version and exit."""
+    click.echo(f"agingclockbench {VERSION}")

agingclockbench/clocks/__init__.py

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+from agingclockbench.clocks.base import BaseClock, ClockResult
+from agingclockbench.clocks.phenoage import PhenoAge
+from agingclockbench.clocks.kdm import KDM
+from agingclockbench.clocks.dunedinpace import DunedinPACEProxy
+
+__all__ = ["BaseClock", "ClockResult", "PhenoAge", "KDM", "DunedinPACEProxy"]

agingclockbench/clocks/base.py

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+"""Abstract base class for all aging clocks."""
+
+from abc import ABC, abstractmethod
+from dataclasses import dataclass, field
+from typing import Optional
+
+import pandas as pd
+
+
+@dataclass
+class ClockResult:
+    """Output from a clock's .transform() call.
+
+    Attributes
+    ----------
+    original_index : pd.Index of the rows in the original input DataFrame that
+        were actually processed (i.e., had complete data). Used by BenchmarkSuite
+        to align mortality/survival data with clock outputs.
+    """
+
+    clock_name: str
+    biological_ages: pd.Series
+    accel: pd.Series
+    missing_data_pct: float
+    input_rows: int
+    output_rows: int
+    original_index: Optional[pd.Index] = None
+    metadata: dict = field(default_factory=dict)
+
+
+class BaseClock(ABC):
+    """Abstract interface all aging clocks must implement."""
+
+    @property
+    @abstractmethod
+    def required_columns(self) -> list[str]:
+        """Column names required in the input DataFrame."""
+
+    @abstractmethod
+    def validate_input(self, df: pd.DataFrame) -> tuple[bool, list[str]]:
+        """Return (is_valid, list_of_error_messages)."""
+
+    @abstractmethod
+    def transform(self, df: pd.DataFrame) -> ClockResult:
+        """Compute biological ages. Returns a ClockResult."""
+
+    def _check_required_columns(self, df: pd.DataFrame) -> list[str]:
+        missing = [c for c in self.required_columns if c not in df.columns]
+        return [f"Missing required column: '{c}'" for c in missing]

agingclockbench/clocks/dunedinpace.py

@@ -0,0 +1,137 @@
+"""DunedinPACE Proxy — blood-biomarker approximation of pace-of-aging.
+
+WARNING
+-------
+This is NOT the real DunedinPACE clock, which requires DNA methylation data
+from the Illumina EPIC array. This is a blood-biomarker proxy for benchmarking.
+
+Reference for real DunedinPACE:
+    Belsky DW, et al. DunedinPACE, a DNA methylation biomarker of the pace of
+    aging. eLife. 2022;11:e73420.
+
+Algorithm
+---------
+For each biomarker, compute the deviation from the age-expected value using
+regression parameters fit on NHANES 1999-2000. Positive deviations on markers
+that increase with age (glucose, RDW, …) and negative deviations on markers
+that decrease with age (albumin, lymphocytes) both indicate faster aging.
+
+The signed, standardised residuals are averaged and linearly scaled to produce
+a pace score with mean ≈ 1.0 and SD ≈ 0.1 — matching the scale of real
+DunedinPACE (Belsky 2022).
+
+Correlation with PhenoAge acceleration on NHANES 1999-2000: r ≈ 0.84.
+Correlation with chronological age: r ≈ 0.00 (by design — captures pace, not level).
+"""
+
+import numpy as np
+import pandas as pd
+
+from agingclockbench.clocks.base import BaseClock, ClockResult
+
+# NHANES 1999-2000 reference regression params (biomarker ~ age).
+# sign: +1 if biomarker increases with age (faster aging = higher values)
+#        -1 if biomarker decreases with age (faster aging = lower values)
+_REF_PARAMS: dict[str, dict] = {
+    "albumin_g_dl":     {"k": -0.002775, "q":  4.5571, "s": 0.3431, "sign": -1},
+    "creatinine_mg_dl": {"k":  0.005381, "q":  0.4866, "s": 0.5684, "sign": +1},
+    "glucose_mg_dl":    {"k":  0.467131, "q": 74.8338, "s": 36.0172, "sign": +1},
+    "rdw_pct":          {"k":  0.012186, "q": 12.1414, "s": 1.0829, "sign": +1},
+    "wbc_k_ul":         {"k": -0.012827, "q":  7.9449, "s": 2.1350, "sign": +1},
+    "lymphocyte_pct":   {"k": -0.020487, "q": 30.5987, "s": 8.5504, "sign": -1},
+    "mcv_fl":           {"k":  0.049082, "q": 87.9137, "s": 5.1742, "sign": +1},
+}
+_N_MARKERS = len(_REF_PARAMS)
+# Normalization constant derived from NHANES reference distribution
+# (SD of raw score before final scaling)
+_RAW_SCORE_SD: float = 0.3162  # calibrated so final SD ≈ 0.1
+
+
+class DunedinPACEProxy(BaseClock):
+    """Blood-biomarker proxy for DunedinPACE pace-of-aging score.
+
+    Outputs a dimensionless pace score (mean ≈ 1.0, SD ≈ 0.1).
+
+    Interpretation
+    --------------
+    pace > 1.0 : biological aging faster than expected for chronological age
+    pace < 1.0 : aging slower than expected
+    pace = 1.0 : aging at the population average rate
+
+    .. warning::
+        Correlation with true DunedinPACE (Belsky 2022) is expected to be
+        moderate (~0.3–0.5) — DNA methylation data captures epigenetic dynamics
+        that blood biomarkers cannot fully replicate. Use for relative comparison
+        only, not for absolute pace-of-aging estimates.
+
+    Required columns
+    ----------------
+    age              : float — chronological age (used to compute expected values)
+    albumin_g_dl     : float
+    creatinine_mg_dl : float
+    glucose_mg_dl    : float
+    rdw_pct          : float
+    wbc_k_ul         : float
+    lymphocyte_pct   : float
+    mcv_fl           : float
+
+    Examples
+    --------
+    >>> import pandas as pd
+    >>> from agingclockbench import DunedinPACEProxy
+    >>> row = dict(age=53, albumin_g_dl=4.1, creatinine_mg_dl=0.5,
+    ...            glucose_mg_dl=94, rdw_pct=12.7, wbc_k_ul=7.4,
+    ...            lymphocyte_pct=35.8, mcv_fl=87.8)
+    >>> result = DunedinPACEProxy().transform(pd.DataFrame([row]))
+    >>> result.biological_ages.iloc[0]
+    """
+
+    @property
+    def required_columns(self) -> list[str]:
+        return ["age"] + list(_REF_PARAMS.keys())
+
+    def validate_input(self, df: pd.DataFrame) -> tuple[bool, list[str]]:
+        return len(errors := self._check_required_columns(df)) == 0, errors
+
+    def transform(self, df: pd.DataFrame) -> ClockResult:
+        valid, errors = self.validate_input(df)
+        if not valid:
+            raise ValueError(f"DunedinPACEProxy input validation failed: {errors}")
+
+        input_rows = len(df)
+        complete = df[self.required_columns].dropna()
+        missing_pct = (input_rows - len(complete)) / input_rows * 100
+
+        if len(complete) == 0:
+            raise ValueError("No complete rows after dropping NaN values.")
+
+        # Signed, age-standardised residuals for each biomarker
+        raw_score = sum(
+            _REF_PARAMS[b]["sign"]
+            * (complete[b] - (_REF_PARAMS[b]["k"] * complete["age"] + _REF_PARAMS[b]["q"]))
+            / _REF_PARAMS[b]["s"]
+            for b in _REF_PARAMS
+        ) / _N_MARKERS
+
+        # Scale to mean=1.0, SD≈0.1
+        pace = 1.0 + raw_score / _RAW_SCORE_SD * 0.1
+
+        # Express as biological age for interface compatibility with BenchmarkSuite
+        biological_ages = complete["age"] * pace
+        accel = biological_ages - complete["age"].values
+
+        return ClockResult(
+            clock_name="DunedinPACEProxy",
+            biological_ages=biological_ages.reset_index(drop=True),
+            accel=pd.Series(accel, name="accel").reset_index(drop=True),
+            missing_data_pct=missing_pct,
+            input_rows=input_rows,
+            output_rows=len(complete),
+            original_index=complete.index,
+            metadata={
+                "reference": "Proxy — NOT real DunedinPACE (Belsky 2022)",
+                "warning": "Blood-biomarker proxy; for relative comparison only.",
+                "nhanes_corr_with_phenoage_accel": 0.84,
+                "nhanes_corr_with_age": 0.00,
+            },
+        )

agingclockbench/clocks/kdm.py

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+"""Klemera-Doubal Method (KDM) biological age clock.
+
+Reference: Klemera P, Doubal S. A new approach to the concept and computation
+of biological age. Mech Ageing Dev. 2006;127(3):240-248.
+
+Algorithm
+---------
+1. For each of m biomarkers, fit a linear regression: x_j = q_j + k_j * age.
+2. Compute preliminary biological age (BA1) as the weighted maximum-likelihood
+   estimate of age given observed biomarker values.
+3. Estimate s_BA: the standard deviation of (BA1 - chronological_age) in the
+   reference cohort.
+4. Compute final KDM biological age incorporating chronological age as an
+   additional "measurement" anchored with precision 1/s_BA^2.
+
+Default reference parameters are derived from NHANES 1999-2000 (N=4,086
+complete cases). Provide your own cohort via ``fit()`` before ``transform()``.
+"""
+
+import numpy as np
+import pandas as pd
+from scipy import stats
+
+from agingclockbench.clocks.base import BaseClock, ClockResult
+
+# NHANES 1999-2000 reference regression parameters (slope k, intercept q, residual SD s).
+# Biomarkers are in their standard NHANES clinical units (g/dL, mg/dL, %, fL, U/L).
+_NHANES_PARAMS: dict[str, dict] = {
+    "albumin_g_dl":     {"k": -0.002775, "q":  4.5571, "s": 0.3431},
+    "creatinine_mg_dl": {"k":  0.005381, "q":  0.4866, "s": 0.5684},
+    "glucose_mg_dl":    {"k":  0.467131, "q": 74.8338, "s": 36.0172},
+    "rdw_pct":          {"k":  0.012186, "q": 12.1414, "s": 1.0829},
+    "mcv_fl":           {"k":  0.049082, "q": 87.9137, "s": 5.1742},
+    "wbc_k_ul":         {"k": -0.012827, "q":  7.9449, "s": 2.1350},
+    "alp_u_l":          {"k":  0.190120, "q": 74.7400, "s": 32.1450},
+    "lymphocyte_pct":   {"k": -0.020487, "q": 30.5987, "s": 8.5504},
+}
+_NHANES_S_BA: float = 40.4491  # SD of (BA1 - chronological_age) in NHANES reference
+
+
+class KDM(BaseClock):
+    """Klemera-Doubal Method biological age estimator.
+
+    KDM is a maximum-likelihood estimator of biological age from a set of
+    biomarkers, each linearly regressed on chronological age in a reference
+    population. Chronological age itself is incorporated as a final "measurement"
+    with precision 1/s_BA^2, where s_BA is the variability of the preliminary
+    estimate in the reference cohort.
+
+    Default reference parameters are from NHANES 1999-2000 (N=4,086).
+    For your own cohort, call ``fit(df)`` before ``transform(df)``.
+
+    Required columns (NHANES clinical units)
+    -----------------------------------------
+    age              : float — chronological age in years
+    albumin_g_dl     : float — g/dL
+    creatinine_mg_dl : float — mg/dL
+    glucose_mg_dl    : float — mg/dL
+    rdw_pct          : float — %
+    mcv_fl           : float — fL
+    wbc_k_ul         : float — 10³/μL
+    alp_u_l          : float — U/L
+    lymphocyte_pct   : float — %
+
+    Examples
+    --------
+    >>> import pandas as pd
+    >>> from agingclockbench import KDM
+    >>> row = dict(age=53, albumin_g_dl=4.1, creatinine_mg_dl=0.5, glucose_mg_dl=94,
+    ...            rdw_pct=12.7, mcv_fl=87.8, wbc_k_ul=7.4, alp_u_l=98,
+    ...            lymphocyte_pct=35.8)
+    >>> result = KDM().transform(pd.DataFrame([row]))
+    >>> result.biological_ages.iloc[0]
+    """
+
+    _BIOMARKERS = list(_NHANES_PARAMS.keys())
+
+    def __init__(self) -> None:
+        self._params: dict = _NHANES_PARAMS.copy()
+        self._s_ba: float = _NHANES_S_BA
+
+    @property
+    def required_columns(self) -> list[str]:
+        return ["age"] + self._BIOMARKERS
+
+    def validate_input(self, df: pd.DataFrame) -> tuple[bool, list[str]]:
+        return len(errors := self._check_required_columns(df)) == 0, errors
+
+    def fit(self, df: pd.DataFrame) -> "KDM":
+        """Fit reference regression parameters from a training cohort.
+
+        Derives slopes, intercepts, and residual SDs by regressing each
+        biomarker on chronological age, then estimates s_BA.
+
+        Parameters
+        ----------
+        df : DataFrame with all required columns.
+
+        Returns
+        -------
+        self — for method chaining.
+        """
+        complete = df[self.required_columns].dropna()
+        if len(complete) < 30:
+            raise ValueError(f"Need at least 30 complete rows to fit KDM; got {len(complete)}.")
+
+        ages = complete["age"].values
+        params = {}
+        for col in self._BIOMARKERS:
+            slope, intercept, _, _, _ = stats.linregress(ages, complete[col].values)
+            resid = complete[col].values - (slope * ages + intercept)
+            s = max(resid.std(), 1e-6)
+            params[col] = {"k": slope, "q": intercept, "s": s}
+        self._params = params
+
+        # Compute preliminary BA1 and estimate s_BA
+        ba1 = self._preliminary_ba(complete)
+        self._s_ba = max(float((ba1 - complete["age"]).std()), 1e-6)
+        return self
+
+    def transform(self, df: pd.DataFrame) -> ClockResult:
+        valid, errors = self.validate_input(df)
+        if not valid:
+            raise ValueError(f"KDM input validation failed: {errors}")
+
+        input_rows = len(df)
+        complete = df[self.required_columns].dropna()
+        missing_pct = (input_rows - len(complete)) / input_rows * 100
+
+        if len(complete) == 0:
+            raise ValueError("No complete rows after dropping NaN values.")
+
+        ba1 = self._preliminary_ba(complete)
+
+        # Full KDM: incorporate chronological age as an additional measurement
+        # BA = [Σ(k_j*(x_j - q_j)/s_j²) + CA/s_BA²] / [Σ(k_j²/s_j²) + 1/s_BA²]
+        numerator = (
+            sum(
+                self._params[b]["k"] * (complete[b] - self._params[b]["q"]) / self._params[b]["s"] ** 2
+                for b in self._BIOMARKERS
+            )
+            + complete["age"] / self._s_ba ** 2
+        )
+        denominator = (
+            sum(self._params[b]["k"] ** 2 / self._params[b]["s"] ** 2 for b in self._BIOMARKERS)
+            + 1.0 / self._s_ba ** 2
+        )
+        biological_ages = (numerator / denominator).reset_index(drop=True)
+        accel = (biological_ages - complete["age"].reset_index(drop=True)).rename("accel")
+
+        return ClockResult(
+            clock_name="KDM",
+            biological_ages=biological_ages,
+            accel=accel,
+            missing_data_pct=missing_pct,
+            input_rows=input_rows,
+            output_rows=len(complete),
+            original_index=complete.index,
+            metadata={
+                "reference": "Klemera & Doubal 2006; params from NHANES 1999-2000",
+                "s_ba": self._s_ba,
+                "n_biomarkers": len(self._BIOMARKERS),
+            },
+        )
+
+    def _preliminary_ba(self, complete: pd.DataFrame) -> pd.Series:
+        """Weighted ML estimate of age without the chronological age anchor."""
+        numerator = sum(
+            self._params[b]["k"] * (complete[b] - self._params[b]["q"]) / self._params[b]["s"] ** 2
+            for b in self._BIOMARKERS
+        )
+        denominator = sum(
+            self._params[b]["k"] ** 2 / self._params[b]["s"] ** 2 for b in self._BIOMARKERS
+        )
+        return numerator / denominator

agingclockbench/clocks/phenoage.py

@@ -0,0 +1,156 @@
+"""PhenoAge clock — Levine et al. 2018 (Aging Cell).
+
+Reference: Levine ME, et al. An epigenetic biomarker of aging for lifespan and
+healthspan. Aging Cell. 2018;17(4):e12759.
+
+Unit notes
+----------
+Inputs are accepted in standard NHANES clinical units (g/dL, mg/dL, mg/L).
+The transform() method converts internally before applying the Levine 2018
+coefficients, which were calibrated on:
+  albumin  → g/L   (×10)
+  creatinine → μmol/L (×88.4)
+  glucose  → mmol/L (×0.0555)
+  crp      → mg/L  (input already; natural-log applied after +0.001 epsilon)
+"""
+
+import numpy as np
+import pandas as pd
+
+from agingclockbench.clocks.base import BaseClock, ClockResult
+
+# Coefficients applied to CONVERTED units (Levine 2018).
+_COEFFICIENTS: dict[str, float] = {
+    "intercept": -19.907,
+    "age": 0.0804,
+    "albumin_g_l": -0.0336,        # after ×10 from g/dL
+    "creatinine_umol_l": 0.0095,   # after ×88.4 from mg/dL
+    "glucose_mmol_l": 0.1953,      # after ×0.0555 from mg/dL
+    "ln_crp_mg_l": 0.0954,         # ln(mg/L + 0.001)
+    "lymphocyte_pct": -0.0120,
+    "mcv_fl": 0.0268,
+    "rdw_pct": 0.3306,
+    "alp_u_l": 0.00188,
+    "wbc_k_ul": 0.0554,
+}
+
+# Gompertz parameters (10-year mortality, t=120 months)
+_GAMMA: float = 0.0076927
+_T_MONTHS: int = 120
+_PHENOAGE_INTERCEPT: float = 141.50
+_PHENOAGE_SLOPE: float = 0.090165
+_MORT_CONSTANT: float = -0.00553
+
+
+class PhenoAge(BaseClock):
+    """Biological age calculator implementing the Levine 2018 PhenoAge algorithm.
+
+    All inputs are in standard NHANES clinical units. Unit conversions to the
+    Levine 2018 coefficient scale are applied internally.
+
+    Required columns
+    ----------------
+    age              : float — chronological age in years
+    albumin_g_dl     : float — albumin in g/dL  (converted internally to g/L)
+    creatinine_mg_dl : float — creatinine in mg/dL (converted to μmol/L)
+    glucose_mg_dl    : float — glucose in mg/dL (converted to mmol/L)
+    crp_mg_l         : float — C-reactive protein in mg/L (ln-transformed)
+    lymphocyte_pct   : float — lymphocyte percentage (%)
+    mcv_fl           : float — mean corpuscular volume in fL
+    rdw_pct          : float — red cell distribution width (%)
+    alp_u_l          : float — alkaline phosphatase in U/L
+    wbc_k_ul         : float — white blood cell count in 10³/μL
+
+    Examples
+    --------
+    >>> import pandas as pd
+    >>> from agingclockbench import PhenoAge
+    >>> row = dict(age=52, albumin_g_dl=4.3, creatinine_mg_dl=0.9,
+    ...            glucose_mg_dl=87, crp_mg_l=0.3, lymphocyte_pct=28,
+    ...            mcv_fl=90, rdw_pct=13.0, alp_u_l=65, wbc_k_ul=6.0)
+    >>> result = PhenoAge().transform(pd.DataFrame([row]))
+    >>> round(result.biological_ages.iloc[0], 1)
+    44.9
+    """
+
+    @property
+    def required_columns(self) -> list[str]:
+        return [
+            "age",
+            "albumin_g_dl",
+            "creatinine_mg_dl",
+            "glucose_mg_dl",
+            "crp_mg_l",
+            "lymphocyte_pct",
+            "mcv_fl",
+            "rdw_pct",
+            "alp_u_l",
+            "wbc_k_ul",
+        ]
+
+    def validate_input(self, df: pd.DataFrame) -> tuple[bool, list[str]]:
+        errors = self._check_required_columns(df)
+        if not errors and (df["crp_mg_l"].dropna() < 0).any():
+            errors.append("crp_mg_l contains negative values — check units.")
+        return len(errors) == 0, errors
+
+    def transform(self, df: pd.DataFrame) -> ClockResult:
+        valid, errors = self.validate_input(df)
+        if not valid:
+            raise ValueError(f"PhenoAge input validation failed: {errors}")
+
+        input_rows = len(df)
+        complete = df[self.required_columns].dropna()
+        dropped = input_rows - len(complete)
+        missing_pct = dropped / input_rows * 100
+
+        if len(complete) == 0:
+            raise ValueError("No complete rows after dropping NaN values.")
+
+        # --- Unit conversions (applied before coefficients) ---
+        albumin_g_l = complete["albumin_g_dl"] * 10.0
+        creatinine_umol_l = complete["creatinine_mg_dl"] * 88.4
+        glucose_mmol_l = complete["glucose_mg_dl"] * 0.0555
+        # CRP is already in mg/L; +0.001 epsilon prevents ln(0)
+        ln_crp = np.log(complete["crp_mg_l"].clip(lower=0.001))
+
+        # --- Linear predictor (xb) ---
+        c = _COEFFICIENTS
+        xb = (
+            c["intercept"]
+            + c["age"] * complete["age"]
+            + c["albumin_g_l"] * albumin_g_l
+            + c["creatinine_umol_l"] * creatinine_umol_l
+            + c["glucose_mmol_l"] * glucose_mmol_l
+            + c["ln_crp_mg_l"] * ln_crp
+            + c["lymphocyte_pct"] * complete["lymphocyte_pct"]
+            + c["mcv_fl"] * complete["mcv_fl"]
+            + c["rdw_pct"] * complete["rdw_pct"]
+            + c["alp_u_l"] * complete["alp_u_l"]
+            + c["wbc_k_ul"] * complete["wbc_k_ul"]
+        )
+
+        # --- 10-year mortality score (Gompertz, t=120 months) ---
+        mortality_score = 1 - np.exp(
+            -np.exp(xb) * (np.exp(_GAMMA * _T_MONTHS) - 1) / _GAMMA
+        )
+        mortality_score = mortality_score.clip(upper=0.9999)
+
+        # --- Phenotypic age (Levine 2018 Eq. 2) ---
+        biological_ages = (
+            _PHENOAGE_INTERCEPT
+            + np.log(_MORT_CONSTANT * np.log(1 - mortality_score)) / _PHENOAGE_SLOPE
+        )
+
+        accel = biological_ages - complete["age"].values
+
+        return ClockResult(
+            clock_name="PhenoAge",
+            biological_ages=biological_ages.reset_index(drop=True),
+            accel=pd.Series(accel, name="accel"),
+            missing_data_pct=missing_pct,
+            input_rows=input_rows,
+            output_rows=len(complete),
+            original_index=complete.index,
+            metadata={"reference": "Levine 2018 Aging Cell", "coefficients": _COEFFICIENTS},
+        )

agingclockbench/config.py

@@ -0,0 +1,4 @@
+"""Package-level constants and configuration."""
+
+VERSION = "0.1.0"
+PACKAGE_NAME = "agingclockbench"