@ottolab/bio-age 0.1.0

package/__tests__/kdm.test.ts

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+import { describe, it, expect } from 'vitest';
+import { calculateKDM, KDM_REGRESSIONS, AGE_VARIANCE } from '../src/kdm.js';
+import type { KDMInput } from '../src/kdm.js';
+
+// Reference healthy 50-year-old with typical biomarkers
+const HEALTHY_50: KDMInput = {
+  chronologicalAge: 50,
+  albumin: 4.0,
+  creatinine: 0.96,
+  glucose: 97,
+  lnCRP: -0.94,
+  lymphocytePercent: 30,
+  mcv: 90,
+  rdw: 13.3,
+  alp: 75,
+  wbc: 7.0,
+  systolicBP: 120,
+  bun: 14,
+  hba1c: 5.5,
+  totalCholesterol: 200,
+};
+
+// Unhealthy profile with accelerated aging markers
+const UNHEALTHY_50: KDMInput = {
+  chronologicalAge: 50,
+  albumin: 3.2,
+  creatinine: 1.4,
+  glucose: 145,
+  lnCRP: 1.0,
+  lymphocytePercent: 18,
+  mcv: 98,
+  rdw: 15.5,
+  alp: 130,
+  wbc: 10.5,
+  systolicBP: 155,
+  bun: 25,
+  hba1c: 7.0,
+  totalCholesterol: 260,
+};
+
+describe('KDM_REGRESSIONS', () => {
+  it('should have 13 biomarker regressions', () => {
+    expect(Object.keys(KDM_REGRESSIONS).length).toBe(13);
+  });
+
+  it('should have positive residual SD for all markers', () => {
+    for (const [, reg] of Object.entries(KDM_REGRESSIONS)) {
+      expect(reg.s).toBeGreaterThan(0);
+    }
+  });
+
+  it('should have albumin declining with age (negative slope)', () => {
+    expect(KDM_REGRESSIONS.albumin.k).toBeLessThan(0);
+  });
+
+  it('should have systolic BP increasing with age (positive slope)', () => {
+    expect(KDM_REGRESSIONS.systolicBP.k).toBeGreaterThan(0);
+  });
+
+  it('should export AGE_VARIANCE as a positive number', () => {
+    expect(AGE_VARIANCE).toBeGreaterThan(0);
+  });
+});
+
+describe('calculateKDM', () => {
+  it('should return a reasonable KDM age for a healthy 50-year-old', () => {
+    const result = calculateKDM(HEALTHY_50);
+    expect(result.kdmAge).toBeGreaterThan(30);
+    expect(result.kdmAge).toBeLessThan(70);
+    expect(result.markersUsed).toBe(13);
+  });
+
+  it('delta should equal kdmAge - chronologicalAge', () => {
+    const result = calculateKDM(HEALTHY_50);
+    expect(result.delta).toBeCloseTo(result.kdmAge - 50, 1);
+  });
+
+  it('should show older KDM age for unhealthy biomarkers', () => {
+    const healthy = calculateKDM(HEALTHY_50);
+    const unhealthy = calculateKDM(UNHEALTHY_50);
+    expect(unhealthy.kdmAge).toBeGreaterThan(healthy.kdmAge);
+    expect(unhealthy.delta).toBeGreaterThan(healthy.delta);
+  });
+
+  it('should work with minimum 3 markers', () => {
+    const minimal: KDMInput = {
+      chronologicalAge: 45,
+      albumin: 4.0,
+      glucose: 95,
+      systolicBP: 118,
+    };
+    const result = calculateKDM(minimal);
+    expect(result.markersUsed).toBe(3);
+    expect(Number.isFinite(result.kdmAge)).toBe(true);
+  });
+
+  it('should throw with fewer than 3 markers', () => {
+    const tooFew: KDMInput = {
+      chronologicalAge: 45,
+      albumin: 4.0,
+      glucose: 95,
+    };
+    expect(() => calculateKDM(tooFew)).toThrow('at least 3 biomarkers');
+  });
+
+  it('should throw with only chronological age', () => {
+    expect(() => calculateKDM({ chronologicalAge: 45 })).toThrow('at least 3 biomarkers');
+  });
+
+  it('should return rounded values to 2 decimal places', () => {
+    const result = calculateKDM(HEALTHY_50);
+    expect(result.kdmAge).toBe(Math.round(result.kdmAge * 100) / 100);
+    expect(result.delta).toBe(Math.round(result.delta * 100) / 100);
+  });
+
+  it('should work for a young person (age 25)', () => {
+    const young: KDMInput = {
+      chronologicalAge: 25,
+      albumin: 4.5,
+      creatinine: 0.85,
+      glucose: 85,
+      lnCRP: -1.5,
+      lymphocytePercent: 33,
+      mcv: 88,
+      rdw: 12.5,
+      alp: 65,
+      wbc: 6.5,
+      systolicBP: 110,
+      bun: 12,
+      hba1c: 5.1,
+      totalCholesterol: 175,
+    };
+    const result = calculateKDM(young);
+    expect(result.kdmAge).toBeGreaterThan(10);
+    expect(result.kdmAge).toBeLessThan(45);
+  });
+
+  it('should work for elderly person (age 80)', () => {
+    const elderly: KDMInput = {
+      chronologicalAge: 80,
+      albumin: 3.5,
+      creatinine: 1.1,
+      glucose: 115,
+      lnCRP: 0.5,
+      lymphocytePercent: 22,
+      mcv: 94,
+      rdw: 14.5,
+      alp: 95,
+      wbc: 6.0,
+      systolicBP: 145,
+      bun: 20,
+      hba1c: 5.9,
+      totalCholesterol: 210,
+    };
+    const result = calculateKDM(elderly);
+    expect(result.kdmAge).toBeGreaterThan(60);
+    expect(Number.isFinite(result.kdmAge)).toBe(true);
+  });
+
+  it('should handle partial marker sets (5-6 markers)', () => {
+    const partial: KDMInput = {
+      chronologicalAge: 40,
+      glucose: 100,
+      hba1c: 5.6,
+      systolicBP: 125,
+      albumin: 4.1,
+      creatinine: 0.9,
+    };
+    const result = calculateKDM(partial);
+    expect(result.markersUsed).toBe(5);
+    expect(Number.isFinite(result.kdmAge)).toBe(true);
+  });
+
+  it('should produce consistent results (deterministic)', () => {
+    const r1 = calculateKDM(HEALTHY_50);
+    const r2 = calculateKDM(HEALTHY_50);
+    expect(r1.kdmAge).toBe(r2.kdmAge);
+    expect(r1.delta).toBe(r2.delta);
+  });
+
+  it('should be sensitive to individual marker changes', () => {
+    const base = calculateKDM(HEALTHY_50);
+    const highBP = calculateKDM({ ...HEALTHY_50, systolicBP: 160 });
+    // Higher BP should increase KDM age
+    expect(highBP.kdmAge).toBeGreaterThan(base.kdmAge);
+  });
+});

package/__tests__/pheno-age.test.ts

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+import { describe, it, expect } from 'vitest';
+import {
+  calculatePhenoAge,
+  calculateMetabolicProxy,
+  computeLinearPredictor,
+  computeMortalityScore,
+  invertToPhenoAge,
+  convertToPhenoAgeUnits,
+  PHENO_AGE_COEFFICIENTS,
+  GAMMA,
+} from '../src/pheno-age.js';
+import type { PhenoAgeInput, MetabolicProxyInput } from '../src/pheno-age.js';
+
+// Reference healthy 40-year-old with population-mean biomarkers
+// Glucose in mmol/L (5.42 ≈ 97.7 mg/dL)
+const HEALTHY_40: PhenoAgeInput = {
+  chronologicalAge: 40,
+  albumin: 4.0, // g/dL
+  creatinine: 0.96, // mg/dL
+  glucose: 5.42, // mmol/L (~97.7 mg/dL)
+  lnCRP: -0.94, // ln(CRP) ~ 0.39 mg/dL
+  lymphocytePercent: 30.3,
+  mcv: 89.5, // fL
+  rdw: 13.3, // %
+  alp: 78.5, // U/L
+  wbc: 7.1, // 10^3/uL
+};
+
+// Unhealthy profile: elevated glucose, CRP, low albumin
+const UNHEALTHY_55: PhenoAgeInput = {
+  chronologicalAge: 55,
+  albumin: 3.2,
+  creatinine: 1.3,
+  glucose: 7.77, // mmol/L (~140 mg/dL)
+  lnCRP: 1.1, // CRP ~ 3 mg/dL
+  lymphocytePercent: 18,
+  mcv: 98,
+  rdw: 15.5,
+  alp: 120,
+  wbc: 10.5,
+};
+
+describe('PHENO_AGE_COEFFICIENTS', () => {
+  it('should have correct Levine 2018 values', () => {
+    expect(PHENO_AGE_COEFFICIENTS.intercept).toBe(-19.9067);
+    expect(PHENO_AGE_COEFFICIENTS.albumin).toBe(-0.0336);
+    expect(PHENO_AGE_COEFFICIENTS.creatinine).toBe(0.0095);
+    expect(PHENO_AGE_COEFFICIENTS.glucose).toBe(0.1953);
+    expect(PHENO_AGE_COEFFICIENTS.lnCRP).toBe(0.0954);
+    expect(PHENO_AGE_COEFFICIENTS.lymphocytePercent).toBe(-0.012);
+    expect(PHENO_AGE_COEFFICIENTS.mcv).toBe(0.0268);
+    expect(PHENO_AGE_COEFFICIENTS.rdw).toBe(0.3306);
+    expect(PHENO_AGE_COEFFICIENTS.alp).toBe(0.00188);
+    expect(PHENO_AGE_COEFFICIENTS.wbc).toBe(0.0554);
+    expect(PHENO_AGE_COEFFICIENTS.age).toBe(0.0804);
+  });
+
+  it('should export gamma constant', () => {
+    expect(GAMMA).toBe(0.0076927);
+  });
+});
+
+describe('computeLinearPredictor', () => {
+  it('should compute xb from coefficients and markers', () => {
+    const xb = computeLinearPredictor(HEALTHY_40);
+    expect(typeof xb).toBe('number');
+    expect(Number.isFinite(xb)).toBe(true);
+    // With population-mean markers, xb should be negative (reasonable mortality)
+    expect(xb).toBeLessThan(0);
+  });
+
+  it('should increase with worse biomarkers', () => {
+    const xbHealthy = computeLinearPredictor(HEALTHY_40);
+    const xbUnhealthy = computeLinearPredictor(UNHEALTHY_55);
+    expect(xbUnhealthy).toBeGreaterThan(xbHealthy);
+  });
+
+  it('should be linear: changing one marker shifts xb proportionally', () => {
+    const base = computeLinearPredictor(HEALTHY_40);
+    const withHighGlucose = computeLinearPredictor({ ...HEALTHY_40, glucose: 7.42 }); // +2 mmol/L
+    const diff = withHighGlucose - base;
+    expect(diff).toBeCloseTo(2 * PHENO_AGE_COEFFICIENTS.glucose, 4);
+  });
+});
+
+describe('computeMortalityScore', () => {
+  it('should return a value between 0 and 1 for typical xb', () => {
+    // Healthy xb is around -8 to -9
+    const m = computeMortalityScore(-9);
+    expect(m).toBeGreaterThan(0);
+    expect(m).toBeLessThan(1);
+  });
+
+  it('should increase monotonically with xb', () => {
+    const m1 = computeMortalityScore(-12);
+    const m2 = computeMortalityScore(-10);
+    const m3 = computeMortalityScore(-8);
+    expect(m2).toBeGreaterThan(m1);
+    expect(m3).toBeGreaterThan(m2);
+  });
+
+  it('should approach 1 for very high xb', () => {
+    const m = computeMortalityScore(0);
+    expect(m).toBeGreaterThan(0.99);
+  });
+
+  it('should be near 0 for very low xb', () => {
+    const m = computeMortalityScore(-20);
+    expect(m).toBeLessThan(0.01);
+  });
+});
+
+describe('invertToPhenoAge', () => {
+  it('should produce a finite age for typical mortality scores', () => {
+    const age = invertToPhenoAge(0.5);
+    expect(Number.isFinite(age)).toBe(true);
+    expect(age).toBeGreaterThan(0);
+    expect(age).toBeLessThan(150);
+  });
+
+  it('should increase monotonically with mortality score', () => {
+    const a1 = invertToPhenoAge(0.3);
+    const a2 = invertToPhenoAge(0.5);
+    const a3 = invertToPhenoAge(0.8);
+    expect(a2).toBeGreaterThan(a1);
+    expect(a3).toBeGreaterThan(a2);
+  });
+
+  it('should handle edge values near 0 and 1', () => {
+    const low = invertToPhenoAge(0.001);
+    const high = invertToPhenoAge(0.999);
+    expect(Number.isFinite(low)).toBe(true);
+    expect(Number.isFinite(high)).toBe(true);
+    expect(high).toBeGreaterThan(low);
+  });
+});
+
+describe('calculatePhenoAge', () => {
+  it('should return a reasonable PhenoAge for a healthy 40-year-old', () => {
+    const result = calculatePhenoAge(HEALTHY_40);
+    expect(result.isProxy).toBe(false);
+    expect(result.phenoAge).toBeGreaterThan(20);
+    expect(result.phenoAge).toBeLessThan(60);
+    // Delta should be moderate for population-mean markers
+    expect(Math.abs(result.delta)).toBeLessThan(15);
+  });
+
+  it('should show older PhenoAge for unhealthy biomarkers', () => {
+    const healthy = calculatePhenoAge(HEALTHY_40);
+    const unhealthy = calculatePhenoAge(UNHEALTHY_55);
+    // Unhealthy person should have a larger delta (more accelerated aging)
+    expect(unhealthy.delta).toBeGreaterThan(healthy.delta);
+  });
+
+  it('should have higher mortality score for unhealthy profile', () => {
+    const healthy = calculatePhenoAge(HEALTHY_40);
+    const unhealthy = calculatePhenoAge(UNHEALTHY_55);
+    expect(unhealthy.mortalityScore).toBeGreaterThan(healthy.mortalityScore);
+  });
+
+  it('should return rounded values to 2 decimal places', () => {
+    const result = calculatePhenoAge(HEALTHY_40);
+    expect(result.phenoAge).toBe(Math.round(result.phenoAge * 100) / 100);
+    expect(result.delta).toBe(Math.round(result.delta * 100) / 100);
+  });
+
+  it('should include driver analysis', () => {
+    const result = calculatePhenoAge(HEALTHY_40);
+    expect(result.drivers).toBeDefined();
+    expect(result.drivers!.length).toBe(9); // 9 biomarkers
+    for (const d of result.drivers!) {
+      expect(['aging', 'protective']).toContain(d.direction);
+      expect(typeof d.contribution).toBe('number');
+    }
+  });
+
+  it('should sort drivers by absolute contribution', () => {
+    const result = calculatePhenoAge(UNHEALTHY_55);
+    const drivers = result.drivers!;
+    for (let i = 1; i < drivers.length; i++) {
+      expect(Math.abs(drivers[i - 1].contribution)).toBeGreaterThanOrEqual(
+        Math.abs(drivers[i].contribution),
+      );
+    }
+  });
+
+  it('delta should equal phenoAge - chronologicalAge', () => {
+    const result = calculatePhenoAge(HEALTHY_40);
+    expect(result.delta).toBeCloseTo(result.phenoAge - 40, 1);
+  });
+
+  it('should work for a young person (age 20)', () => {
+    const young = { ...HEALTHY_40, chronologicalAge: 20 };
+    const result = calculatePhenoAge(young);
+    expect(result.phenoAge).toBeGreaterThan(0);
+    expect(Number.isFinite(result.phenoAge)).toBe(true);
+  });
+
+  it('should work for an elderly person (age 85)', () => {
+    const elderly: PhenoAgeInput = {
+      chronologicalAge: 85,
+      albumin: 3.5,
+      creatinine: 1.1,
+      glucose: 6.11, // mmol/L (~110 mg/dL)
+      lnCRP: 0.5,
+      lymphocytePercent: 22,
+      mcv: 94,
+      rdw: 14.8,
+      alp: 95,
+      wbc: 6.5,
+    };
+    const result = calculatePhenoAge(elderly);
+    expect(result.phenoAge).toBeGreaterThan(60);
+    expect(Number.isFinite(result.phenoAge)).toBe(true);
+  });
+
+  it('should produce a larger delta when glucose is elevated', () => {
+    const normal = calculatePhenoAge(HEALTHY_40);
+    const highGlucose = calculatePhenoAge({ ...HEALTHY_40, glucose: 8.0 }); // ~144 mg/dL
+    expect(highGlucose.delta).toBeGreaterThan(normal.delta);
+  });
+
+  it('should produce a larger delta when CRP is elevated', () => {
+    const normal = calculatePhenoAge(HEALTHY_40);
+    const highCRP = calculatePhenoAge({ ...HEALTHY_40, lnCRP: 1.5 }); // CRP ~4.5 mg/dL
+    expect(highCRP.delta).toBeGreaterThan(normal.delta);
+  });
+});
+
+describe('calculateMetabolicProxy', () => {
+  it('should return isProxy = true', () => {
+    const result = calculateMetabolicProxy({ chronologicalAge: 40 });
+    expect(result.isProxy).toBe(true);
+  });
+
+  it('should return chronological age when no markers provided', () => {
+    const result = calculateMetabolicProxy({ chronologicalAge: 40 });
+    expect(result.phenoAge).toBe(40);
+    expect(result.delta).toBe(0);
+  });
+
+  it('should show positive delta for unhealthy metabolic markers', () => {
+    const input: MetabolicProxyInput = {
+      chronologicalAge: 45,
+      glucose: 140, // high
+      hba1c: 6.8, // high
+      hsCrp: 8.0, // high
+      triglycerides: 300, // high
+      hdl: 35, // low
+      fastingInsulin: 20, // high
+      uricAcid: 8.0, // high
+    };
+    const result = calculateMetabolicProxy(input);
+    expect(result.delta).toBeGreaterThan(0);
+    expect(result.phenoAge).toBeGreaterThan(45);
+  });
+
+  it('should show negative delta for excellent metabolic markers', () => {
+    const input: MetabolicProxyInput = {
+      chronologicalAge: 50,
+      glucose: 80,
+      hba1c: 4.9,
+      hsCrp: 0.3,
+      triglycerides: 60,
+      hdl: 75,
+      fastingInsulin: 3,
+      uricAcid: 3.5,
+    };
+    const result = calculateMetabolicProxy(input);
+    expect(result.delta).toBeLessThan(0);
+    expect(result.phenoAge).toBeLessThan(50);
+  });
+
+  it('should clamp delta to [-10, +15]', () => {
+    const extreme: MetabolicProxyInput = {
+      chronologicalAge: 40,
+      glucose: 300,
+      hba1c: 12,
+      hsCrp: 50,
+      triglycerides: 800,
+      fastingInsulin: 60,
+      uricAcid: 15,
+    };
+    const result = calculateMetabolicProxy(extreme);
+    expect(result.delta).toBeLessThanOrEqual(15);
+    expect(result.delta).toBeGreaterThanOrEqual(-10);
+  });
+
+  it('should work with a subset of markers', () => {
+    const partial: MetabolicProxyInput = {
+      chronologicalAge: 35,
+      glucose: 95,
+      hsCrp: 1.5,
+    };
+    const result = calculateMetabolicProxy(partial);
+    expect(Number.isFinite(result.phenoAge)).toBe(true);
+    expect(result.isProxy).toBe(true);
+  });
+
+  it('should return rounded values', () => {
+    const input: MetabolicProxyInput = {
+      chronologicalAge: 40,
+      glucose: 110,
+      hba1c: 5.8,
+    };
+    const result = calculateMetabolicProxy(input);
+    expect(result.phenoAge).toBe(Math.round(result.phenoAge * 100) / 100);
+    expect(result.delta).toBe(Math.round(result.delta * 100) / 100);
+  });
+});
+
+describe('convertToPhenoAgeUnits', () => {
+  it('should convert albumin from g/L to g/dL', () => {
+    const result = convertToPhenoAgeUnits({ albumin_gL: 40 });
+    expect(result.albumin).toBeCloseTo(4.0, 4);
+  });
+
+  it('should convert creatinine from umol/L to mg/dL', () => {
+    const result = convertToPhenoAgeUnits({ creatinine_umolL: 88.4 });
+    expect(result.creatinine).toBeCloseTo(1.0, 2);
+  });
+
+  it('should convert glucose from mg/dL to mmol/L', () => {
+    const result = convertToPhenoAgeUnits({ glucose_mgDL: 90 });
+    expect(result.glucose).toBeCloseTo(90 / 18.0182, 2);
+  });
+
+  it('should pass through glucose in mmol/L', () => {
+    const result = convertToPhenoAgeUnits({ glucose_mmolL: 5.0 });
+    expect(result.glucose).toBe(5.0);
+  });
+
+  it('should convert CRP from mg/L to ln(mg/dL)', () => {
+    const result = convertToPhenoAgeUnits({ crp_mgL: 1.0 });
+    // 1.0 mg/L → 0.1 mg/dL → ln(0.1) ≈ -2.302
+    expect(result.lnCRP).toBeCloseTo(Math.log(0.1), 2);
+  });
+
+  it('should handle CRP floor for very low values', () => {
+    const result = convertToPhenoAgeUnits({ crp_mgL: 0 });
+    expect(result.lnCRP).toBeCloseTo(Math.log(0.001), 2);
+  });
+
+  it('should pass through direct units unchanged', () => {
+    const result = convertToPhenoAgeUnits({
+      lymphocytePercent: 30,
+      mcv: 90,
+      rdw: 13,
+      alp: 75,
+      wbc: 7,
+    });
+    expect(result.lymphocytePercent).toBe(30);
+    expect(result.mcv).toBe(90);
+    expect(result.rdw).toBe(13);
+    expect(result.alp).toBe(75);
+    expect(result.wbc).toBe(7);
+  });
+
+  it('should return partial result for partial input', () => {
+    const result = convertToPhenoAgeUnits({ albumin_gL: 40 });
+    expect(result.albumin).toBeDefined();
+    expect(result.creatinine).toBeUndefined();
+    expect(result.glucose).toBeUndefined();
+  });
+
+  it('should prefer glucose_mmolL over glucose_mgDL when both provided', () => {
+    const result = convertToPhenoAgeUnits({ glucose_mgDL: 90, glucose_mmolL: 5.0 });
+    // glucose_mmolL is processed after glucose_mgDL, so it wins
+    expect(result.glucose).toBe(5.0);
+  });
+});

package/__tests__/utils.test.ts

@@ -0,0 +1,67 @@
+import { describe, it, expect } from 'vitest';
+import { clamp, safeLn } from '../src/utils.js';
+
+describe('clamp', () => {
+  it('should return value when within range', () => {
+    expect(clamp(5, 0, 10)).toBe(5);
+    expect(clamp(0, 0, 10)).toBe(0);
+    expect(clamp(10, 0, 10)).toBe(10);
+  });
+
+  it('should clamp to min when below range', () => {
+    expect(clamp(-5, 0, 10)).toBe(0);
+    expect(clamp(-100, -10, 10)).toBe(-10);
+  });
+
+  it('should clamp to max when above range', () => {
+    expect(clamp(15, 0, 10)).toBe(10);
+    expect(clamp(100, -10, 10)).toBe(10);
+  });
+
+  it('should handle equal min and max', () => {
+    expect(clamp(5, 3, 3)).toBe(3);
+    expect(clamp(1, 3, 3)).toBe(3);
+  });
+
+  it('should handle negative ranges', () => {
+    expect(clamp(-5, -10, -1)).toBe(-5);
+    expect(clamp(-15, -10, -1)).toBe(-10);
+    expect(clamp(0, -10, -1)).toBe(-1);
+  });
+
+  it('should handle floating point', () => {
+    expect(clamp(0.5, 0.1, 0.9)).toBe(0.5);
+    expect(clamp(0.05, 0.1, 0.9)).toBe(0.1);
+  });
+});
+
+describe('safeLn', () => {
+  it('should return ln for positive values', () => {
+    expect(safeLn(1)).toBeCloseTo(0, 10);
+    expect(safeLn(Math.E)).toBeCloseTo(1, 10);
+    expect(safeLn(10)).toBeCloseTo(Math.log(10), 10);
+  });
+
+  it('should floor zero to default 0.001', () => {
+    expect(safeLn(0)).toBeCloseTo(Math.log(0.001), 10);
+  });
+
+  it('should floor negative values to default 0.001', () => {
+    expect(safeLn(-5)).toBeCloseTo(Math.log(0.001), 10);
+  });
+
+  it('should use custom floor when provided', () => {
+    expect(safeLn(0, 0.01)).toBeCloseTo(Math.log(0.01), 10);
+    expect(safeLn(-1, 0.1)).toBeCloseTo(Math.log(0.1), 10);
+  });
+
+  it('should not change values above the floor', () => {
+    expect(safeLn(5, 0.01)).toBeCloseTo(Math.log(5), 10);
+  });
+
+  it('should never return -Infinity', () => {
+    expect(Number.isFinite(safeLn(0))).toBe(true);
+    expect(Number.isFinite(safeLn(-100))).toBe(true);
+    expect(Number.isFinite(safeLn(0.0001))).toBe(true);
+  });
+});

package/package.json

@@ -0,0 +1,29 @@
+{
+  "name": "@ottolab/bio-age",
+  "version": "0.1.0",
+  "license": "MIT",
+  "repository": "https://github.com/hokev/Otto",
+  "publishConfig": { "access": "public" },
+  "type": "module",
+  "exports": {
+    ".": {
+      "import": {
+        "types": "./dist/index.d.ts",
+        "default": "./dist/index.js"
+      },
+      "source": "./src/index.ts"
+    }
+  },
+  "scripts": {
+    "build": "tsc --build",
+    "lint": "eslint src/",
+    "test": "vitest run"
+  },
+  "dependencies": {
+    "@ottolab/shared": "*"
+  },
+  "devDependencies": {
+    "@vitest/coverage-v8": "^3.2.4",
+    "vitest": "^3.0.0"
+  }
+}

package/src/index.ts

@@ -0,0 +1,21 @@
+export {
+  calculatePhenoAge,
+  calculateMetabolicProxy,
+  computeLinearPredictor,
+  computeMortalityScore,
+  invertToPhenoAge,
+  convertToPhenoAgeUnits,
+  PHENO_AGE_COEFFICIENTS,
+  GAMMA,
+} from './pheno-age.js';
+export type {
+  PhenoAgeInput,
+  PhenoAgeResult,
+  PhenoAgeDriver,
+  MetabolicProxyInput,
+} from './pheno-age.js';
+
+export { calculateKDM, KDM_REGRESSIONS, AGE_VARIANCE } from './kdm.js';
+export type { KDMInput, KDMResult } from './kdm.js';
+
+export { clamp, safeLn } from './utils.js';

package/src/kdm.ts

@@ -0,0 +1,129 @@
+/**
+ * Klemera-Doubal Method (KDM) Biological Age.
+ *
+ * Based on: Klemera & Doubal (2006) "A new approach to the concept and
+ * computation of biological age". Implemented with biomarker regressions
+ * from NHANES III data following the approach in Levine (2013).
+ *
+ * KDM fits each biomarker as a linear function of chronological age,
+ * then combines all biomarkers into a single BA estimate that minimizes
+ * the sum of squared deviations weighted by residual variance.
+ */
+
+export interface KDMInput {
+  chronologicalAge: number;
+  albumin?: number; // g/dL
+  creatinine?: number; // mg/dL
+  glucose?: number; // mg/dL
+  lnCRP?: number; // ln(CRP mg/dL)
+  lymphocytePercent?: number;
+  mcv?: number; // fL
+  rdw?: number; // %
+  alp?: number; // U/L
+  wbc?: number; // 10^3/uL
+  systolicBP?: number; // mmHg
+  bun?: number; // mg/dL
+  hba1c?: number; // %
+  totalCholesterol?: number; // mg/dL
+}
+
+export interface KDMResult {
+  kdmAge: number;
+  delta: number;
+  markersUsed: number;
+}
+
+/**
+ * Biomarker regression parameters: each marker regressed on chronological age.
+ * slope (k), intercept (q), residual SD (s) from NHANES III reference.
+ *
+ * Model: biomarker_i = q_i + k_i * age + error_i, Var(error_i) = s_i^2
+ */
+interface BiomarkerRegression {
+  k: number; // slope (change per year of age)
+  q: number; // intercept
+  s: number; // residual standard deviation
+}
+
+const KDM_REGRESSIONS: Record<string, BiomarkerRegression> = {
+  albumin: { k: -0.0172, q: 4.703, s: 0.3262 },
+  creatinine: { k: 0.0033, q: 0.842, s: 0.2136 },
+  glucose: { k: 0.27, q: 83.56, s: 22.24 },
+  lnCRP: { k: 0.0205, q: -1.794, s: 1.126 },
+  lymphocytePercent: { k: -0.0522, q: 33.55, s: 8.47 },
+  mcv: { k: 0.052, q: 87.08, s: 5.51 },
+  rdw: { k: 0.0211, q: 12.36, s: 1.18 },
+  alp: { k: 0.347, q: 58.83, s: 24.1 },
+  wbc: { k: -0.0072, q: 7.4, s: 2.12 },
+  systolicBP: { k: 0.527, q: 101.8, s: 17.64 },
+  bun: { k: 0.101, q: 10.89, s: 4.63 },
+  hba1c: { k: 0.0131, q: 4.926, s: 0.607 },
+  totalCholesterol: { k: 0.252, q: 190.2, s: 40.41 },
+};
+
+// Variance of chronological age in reference population (NHANES III, adults 20-85)
+const AGE_VARIANCE = 250.0; // ~SD of 15.8 years
+
+/**
+ * Calculate KDM biological age.
+ *
+ * The KDM formula:
+ *   BA = [ sum_i( (x_i - q_i) * k_i / s_i^2 ) + CA / s_BA^2 ]
+ *        / [ sum_i( k_i^2 / s_i^2 ) + 1 / s_BA^2 ]
+ *
+ * where s_BA^2 is estimated from the age variance in the reference population.
+ *
+ * Requires at least 3 markers for a meaningful estimate.
+ */
+export function calculateKDM(input: KDMInput): KDMResult {
+  const markers = getAvailableMarkers(input);
+
+  if (markers.length < 3) {
+    throw new Error(`KDM requires at least 3 biomarkers, got ${markers.length}`);
+  }
+
+  let numerator = 0;
+  let denominator = 0;
+
+  for (const { value, regression } of markers) {
+    const { k, q, s } = regression;
+    const s2 = s * s;
+    numerator += ((value - q) * k) / s2;
+    denominator += (k * k) / s2;
+  }
+
+  // Add chronological age term (acts as a prior)
+  const sBA2 = AGE_VARIANCE;
+  numerator += input.chronologicalAge / sBA2;
+  denominator += 1 / sBA2;
+
+  const kdmAge = numerator / denominator;
+  const delta = kdmAge - input.chronologicalAge;
+
+  return {
+    kdmAge: Math.round(kdmAge * 100) / 100,
+    delta: Math.round(delta * 100) / 100,
+    markersUsed: markers.length,
+  };
+}
+
+/**
+ * Extract available markers from input, matching to their regression parameters.
+ */
+function getAvailableMarkers(
+  input: KDMInput,
+): { name: string; value: number; regression: BiomarkerRegression }[] {
+  const result: { name: string; value: number; regression: BiomarkerRegression }[] = [];
+
+  for (const [name, regression] of Object.entries(KDM_REGRESSIONS)) {
+    const value = input[name as keyof KDMInput];
+    if (typeof value === 'number') {
+      result.push({ name, value, regression });
+    }
+  }
+
+  return result;
+}
+
+// Export regressions for testing
+export { KDM_REGRESSIONS, AGE_VARIANCE };

package/src/pheno-age.ts

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+import { clamp } from './utils.js';
+
+/**
+ * Input for PhenoAge calculation.
+ * Units follow the Levine 2018 model convention:
+ * albumin g/dL, creatinine mg/dL, glucose mmol/L, CRP mg/dL (log-transformed),
+ * lymphocyte %, MCV fL, RDW %, ALP U/L, WBC 10^3/uL.
+ */
+export interface PhenoAgeInput {
+  chronologicalAge: number;
+  albumin: number; // g/dL
+  creatinine: number; // mg/dL
+  glucose: number; // mmol/L
+  lnCRP: number; // ln(CRP in mg/dL)
+  lymphocytePercent: number;
+  mcv: number; // fL
+  rdw: number; // %
+  alp: number; // U/L
+  wbc: number; // 10^3 cells/uL
+}
+
+export interface PhenoAgeResult {
+  phenoAge: number;
+  delta: number; // phenoAge - chronologicalAge
+  mortalityScore: number;
+  isProxy: boolean;
+  drivers?: PhenoAgeDriver[];
+}
+
+export interface PhenoAgeDriver {
+  marker: string;
+  contribution: number;
+  direction: 'aging' | 'protective';
+}
+
+/**
+ * Input for the metabolic proxy fallback when full CBC is unavailable.
+ * All values in conventional US units.
+ */
+export interface MetabolicProxyInput {
+  chronologicalAge: number;
+  glucose?: number; // mg/dL
+  hba1c?: number; // %
+  hsCrp?: number; // mg/L
+  triglycerides?: number; // mg/dL
+  hdl?: number; // mg/dL
+  ldlC?: number; // mg/dL
+  fastingInsulin?: number; // uIU/mL
+  uricAcid?: number; // mg/dL
+}
+
+// Published coefficients (Levine 2018, Table S6)
+export const PHENO_AGE_COEFFICIENTS = {
+  intercept: -19.9067,
+  albumin: -0.0336,
+  creatinine: 0.0095,
+  glucose: 0.1953,
+  lnCRP: 0.0954,
+  lymphocytePercent: -0.012,
+  mcv: 0.0268,
+  rdw: 0.3306,
+  alp: 0.00188,
+  wbc: 0.0554,
+  age: 0.0804,
+} as const;
+
+// Gompertz proportional hazard gamma
+export const GAMMA = 0.0076927;
+
+// Max age horizon for Gompertz integration
+const MAX_AGE = 120;
+
+// PhenoAge inversion constants (derived from Gompertz model)
+const PHENO_INVERSE = {
+  intercept: 141.50225,
+  lambda: -0.00553,
+  slope: 0.090165,
+} as const;
+
+// Population means for driver analysis (NHANES III reference)
+const POPULATION_MEANS: Record<string, number> = {
+  albumin: 4.0,
+  creatinine: 0.96,
+  glucose: 5.42, // 97.7 mg/dL → mmol/L
+  lnCRP: -0.94,
+  lymphocytePercent: 30.3,
+  mcv: 89.5,
+  rdw: 13.3,
+  alp: 78.5,
+  wbc: 7.1,
+};
+
+// Population means and SDs for metabolic proxy (NHANES reference)
+const METABOLIC_PROXY_MARKERS: Record<string, { mean: number; sd: number; weight: number }> = {
+  glucose: { mean: 97.7, sd: 22, weight: 1.0 },
+  hba1c: { mean: 5.5, sd: 0.5, weight: 1.2 },
+  hsCrp: { mean: 2.0, sd: 3.0, weight: 0.8 },
+  triglycerides: { mean: 130, sd: 75, weight: 0.6 },
+  hdl: { mean: 53, sd: 15, weight: -0.7 }, // negative: higher is better
+  ldlC: { mean: 120, sd: 35, weight: 0.5 },
+  fastingInsulin: { mean: 9.0, sd: 6.0, weight: 0.9 },
+  uricAcid: { mean: 5.4, sd: 1.4, weight: 0.6 },
+};
+
+// Years of biological age per 1 SD deviation
+const YEARS_PER_SD = 2.5;
+
+/**
+ * Compute the linear predictor (xb) from PhenoAge model.
+ */
+export function computeLinearPredictor(input: PhenoAgeInput): number {
+  const c = PHENO_AGE_COEFFICIENTS;
+  return (
+    c.intercept +
+    c.albumin * input.albumin +
+    c.creatinine * input.creatinine +
+    c.glucose * input.glucose +
+    c.lnCRP * input.lnCRP +
+    c.lymphocytePercent * input.lymphocytePercent +
+    c.mcv * input.mcv +
+    c.rdw * input.rdw +
+    c.alp * input.alp +
+    c.wbc * input.wbc +
+    c.age * input.chronologicalAge
+  );
+}
+
+/**
+ * Compute cumulative mortality probability from linear predictor via Gompertz model.
+ *
+ * M(xb) = 1 - exp(-exp(xb) * (exp(gamma * T) - 1) / gamma)
+ * where T = MAX_AGE (120 years)
+ */
+export function computeMortalityScore(xb: number): number {
+  const hazard = Math.exp(xb);
+  const cumHazard = (hazard * (Math.exp(GAMMA * MAX_AGE) - 1)) / GAMMA;
+  return 1 - Math.exp(-cumHazard);
+}
+
+/**
+ * Invert mortality score back to PhenoAge.
+ *
+ * PhenoAge = intercept + ln(lambda * ln(1 - M)) / slope
+ */
+export function invertToPhenoAge(mortalityScore: number): number {
+  const clamped = clamp(mortalityScore, 1e-10, 1 - 1e-10);
+  const inner = PHENO_INVERSE.lambda * Math.log(1 - clamped);
+  return PHENO_INVERSE.intercept + Math.log(inner) / PHENO_INVERSE.slope;
+}
+
+/**
+ * Calculate PhenoAge biological age using the Levine 2018 algorithm.
+ *
+ * Algorithm:
+ * 1. Linear predictor: xb = intercept + sum(coeff_i * marker_i)
+ * 2. Gompertz mortality: M = 1 - exp(-exp(xb) * (exp(gamma*120) - 1) / gamma)
+ * 3. Invert: PhenoAge = 141.50225 + ln(-0.00553 * ln(1-M)) / 0.090165
+ *
+ * All inputs must be in model-native units (g/dL, mg/dL, etc.).
+ * Use `convertToPhenoAgeUnits()` if you have SI units.
+ */
+export function calculatePhenoAge(input: PhenoAgeInput): PhenoAgeResult {
+  const xb = computeLinearPredictor(input);
+  const mortalityScore = computeMortalityScore(xb);
+  const phenoAge = invertToPhenoAge(mortalityScore);
+  const delta = phenoAge - input.chronologicalAge;
+  const drivers = computeDrivers(input);
+
+  return {
+    phenoAge: Math.round(phenoAge * 100) / 100,
+    delta: Math.round(delta * 100) / 100,
+    mortalityScore: Math.round(mortalityScore * 10000) / 10000,
+    isProxy: false,
+    drivers,
+  };
+}
+
+/**
+ * Metabolic proxy for biological age when full CBC panel is unavailable.
+ *
+ * Uses z-score deviation from population means across available metabolic
+ * markers. Each weighted SD of deviation approximates YEARS_PER_SD years
+ * of biological age shift. Delta is capped at [-10, +15] years.
+ */
+export function calculateMetabolicProxy(input: MetabolicProxyInput): PhenoAgeResult {
+  let weightedZSum = 0;
+  let totalWeight = 0;
+
+  for (const [key, config] of Object.entries(METABOLIC_PROXY_MARKERS)) {
+    const value = input[key as keyof MetabolicProxyInput] as number | undefined;
+    if (value === undefined) continue;
+
+    const z = (value - config.mean) / config.sd;
+    weightedZSum += z * config.weight;
+    totalWeight += Math.abs(config.weight);
+  }
+
+  if (totalWeight === 0) {
+    return {
+      phenoAge: input.chronologicalAge,
+      delta: 0,
+      mortalityScore: 0,
+      isProxy: true,
+    };
+  }
+
+  const normalizedZ = weightedZSum / totalWeight;
+  const rawDelta = normalizedZ * YEARS_PER_SD;
+  const delta = clamp(rawDelta, -10, 15);
+  const phenoAge = input.chronologicalAge + delta;
+
+  return {
+    phenoAge: Math.round(phenoAge * 100) / 100,
+    delta: Math.round(delta * 100) / 100,
+    mortalityScore: 0,
+    isProxy: true,
+  };
+}
+
+/**
+ * Identify which biomarkers drive the PhenoAge deviation most.
+ * Computes contribution = coefficient * (actual - population_mean) for each marker.
+ */
+function computeDrivers(input: PhenoAgeInput): PhenoAgeDriver[] {
+  const c = PHENO_AGE_COEFFICIENTS;
+  const markerCoeffs: [string, number, number][] = [
+    ['albumin', c.albumin, input.albumin],
+    ['creatinine', c.creatinine, input.creatinine],
+    ['glucose', c.glucose, input.glucose],
+    ['lnCRP', c.lnCRP, input.lnCRP],
+    ['lymphocytePercent', c.lymphocytePercent, input.lymphocytePercent],
+    ['mcv', c.mcv, input.mcv],
+    ['rdw', c.rdw, input.rdw],
+    ['alp', c.alp, input.alp],
+    ['wbc', c.wbc, input.wbc],
+  ];
+
+  const drivers: PhenoAgeDriver[] = markerCoeffs.map(([marker, coeff, actual]) => {
+    const mean = POPULATION_MEANS[marker] ?? 0;
+    const contribution = coeff * (actual - mean);
+    return {
+      marker,
+      contribution: Math.round(contribution * 10000) / 10000,
+      direction: contribution > 0 ? 'aging' : 'protective',
+    };
+  });
+
+  return drivers.sort((a, b) => Math.abs(b.contribution) - Math.abs(a.contribution));
+}
+
+/**
+ * Convert common lab units to PhenoAge model units.
+ *
+ * Accepts either SI or US units and converts to model-native:
+ * albumin g/L → g/dL, creatinine umol/L → mg/dL, glucose mg/dL → mmol/L,
+ * CRP mg/L → ln(mg/dL).
+ */
+export function convertToPhenoAgeUnits(raw: {
+  albumin_gL?: number;
+  creatinine_umolL?: number;
+  glucose_mgDL?: number;
+  glucose_mmolL?: number;
+  crp_mgL?: number;
+  lymphocytePercent?: number;
+  mcv?: number;
+  rdw?: number;
+  alp?: number;
+  wbc?: number;
+}): Partial<Omit<PhenoAgeInput, 'chronologicalAge'>> {
+  const result: Partial<Omit<PhenoAgeInput, 'chronologicalAge'>> = {};
+
+  if (raw.albumin_gL !== undefined) result.albumin = raw.albumin_gL * 0.1; // g/L → g/dL
+  if (raw.creatinine_umolL !== undefined) result.creatinine = raw.creatinine_umolL / 88.4; // umol/L → mg/dL
+  if (raw.glucose_mgDL !== undefined) result.glucose = raw.glucose_mgDL / 18.0182; // mg/dL → mmol/L
+  if (raw.glucose_mmolL !== undefined) result.glucose = raw.glucose_mmolL; // already mmol/L
+  if (raw.crp_mgL !== undefined) result.lnCRP = Math.log(Math.max(raw.crp_mgL * 0.1, 0.001)); // mg/L → mg/dL → ln
+  if (raw.lymphocytePercent !== undefined) result.lymphocytePercent = raw.lymphocytePercent;
+  if (raw.mcv !== undefined) result.mcv = raw.mcv;
+  if (raw.rdw !== undefined) result.rdw = raw.rdw;
+  if (raw.alp !== undefined) result.alp = raw.alp;
+  if (raw.wbc !== undefined) result.wbc = raw.wbc;
+
+  return result;
+}

package/src/utils.ts

@@ -0,0 +1,13 @@
+/**
+ * Clamp a value to a [min, max] range.
+ */
+export function clamp(value: number, min: number, max: number): number {
+  return Math.min(Math.max(value, min), max);
+}
+
+/**
+ * Natural log with safety floor to avoid -Infinity.
+ */
+export function safeLn(value: number, floor = 0.001): number {
+  return Math.log(Math.max(value, floor));
+}

package/tsconfig.json

@@ -0,0 +1,10 @@
+{
+  "extends": "../../tsconfig.json",
+  "compilerOptions": {
+    "composite": true,
+    "outDir": "dist",
+    "rootDir": "src"
+  },
+  "include": ["src"],
+  "references": [{ "path": "../shared" }]
+}

package/tsconfig.tsbuildinfo

@@ -0,0 +1 @@
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