@ottolab/bio-age 0.1.0 → 0.1.1

package/dist/index.d.ts

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+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';
+//# sourceMappingURL=index.d.ts.map

package/dist/index.d.ts.map

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package/dist/index.js

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+export { calculatePhenoAge, calculateMetabolicProxy, computeLinearPredictor, computeMortalityScore, invertToPhenoAge, convertToPhenoAgeUnits, PHENO_AGE_COEFFICIENTS, GAMMA, } from './pheno-age.js';
+export { calculateKDM, KDM_REGRESSIONS, AGE_VARIANCE } from './kdm.js';
+export { clamp, safeLn } from './utils.js';
+//# sourceMappingURL=index.js.map

package/dist/index.js.map

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package/dist/kdm.d.ts

@@ -0,0 +1,59 @@
+/**
+ * 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;
+    creatinine?: number;
+    glucose?: number;
+    lnCRP?: number;
+    lymphocytePercent?: number;
+    mcv?: number;
+    rdw?: number;
+    alp?: number;
+    wbc?: number;
+    systolicBP?: number;
+    bun?: number;
+    hba1c?: number;
+    totalCholesterol?: number;
+}
+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;
+    q: number;
+    s: number;
+}
+declare const KDM_REGRESSIONS: Record<string, BiomarkerRegression>;
+declare const AGE_VARIANCE = 250;
+/**
+ * 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 declare function calculateKDM(input: KDMInput): KDMResult;
+export { KDM_REGRESSIONS, AGE_VARIANCE };
+//# sourceMappingURL=kdm.d.ts.map

package/dist/kdm.d.ts.map

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package/dist/kdm.js

@@ -0,0 +1,80 @@
+/**
+ * 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.
+ */
+const KDM_REGRESSIONS = {
+    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) {
+    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) {
+    const result = [];
+    for (const [name, regression] of Object.entries(KDM_REGRESSIONS)) {
+        const value = input[name];
+        if (typeof value === 'number') {
+            result.push({ name, value, regression });
+        }
+    }
+    return result;
+}
+// Export regressions for testing
+export { KDM_REGRESSIONS, AGE_VARIANCE };
+//# sourceMappingURL=kdm.js.map

package/dist/kdm.js.map

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package/dist/pheno-age.d.ts

@@ -0,0 +1,116 @@
+/**
+ * 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;
+    creatinine: number;
+    glucose: number;
+    lnCRP: number;
+    lymphocytePercent: number;
+    mcv: number;
+    rdw: number;
+    alp: number;
+    wbc: number;
+}
+export interface PhenoAgeResult {
+    phenoAge: number;
+    delta: number;
+    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;
+    hba1c?: number;
+    hsCrp?: number;
+    triglycerides?: number;
+    hdl?: number;
+    ldlC?: number;
+    fastingInsulin?: number;
+    uricAcid?: number;
+}
+export declare const PHENO_AGE_COEFFICIENTS: {
+    readonly intercept: -19.9067;
+    readonly albumin: -0.0336;
+    readonly creatinine: 0.0095;
+    readonly glucose: 0.1953;
+    readonly lnCRP: 0.0954;
+    readonly lymphocytePercent: -0.012;
+    readonly mcv: 0.0268;
+    readonly rdw: 0.3306;
+    readonly alp: 0.00188;
+    readonly wbc: 0.0554;
+    readonly age: 0.0804;
+};
+export declare const GAMMA = 0.0076927;
+/**
+ * Compute the linear predictor (xb) from PhenoAge model.
+ */
+export declare function computeLinearPredictor(input: PhenoAgeInput): number;
+/**
+ * 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 declare function computeMortalityScore(xb: number): number;
+/**
+ * Invert mortality score back to PhenoAge.
+ *
+ * PhenoAge = intercept + ln(lambda * ln(1 - M)) / slope
+ */
+export declare function invertToPhenoAge(mortalityScore: number): number;
+/**
+ * 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 declare function calculatePhenoAge(input: PhenoAgeInput): PhenoAgeResult;
+/**
+ * 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 declare function calculateMetabolicProxy(input: MetabolicProxyInput): PhenoAgeResult;
+/**
+ * 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 declare 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'>>;
+//# sourceMappingURL=pheno-age.d.ts.map

package/dist/pheno-age.d.ts.map

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package/dist/pheno-age.js

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+import { clamp } from './utils.js';
+// 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,
+};
+// 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,
+};
+// Population means for driver analysis (NHANES III reference)
+const POPULATION_MEANS = {
+    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 = {
+    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) {
+    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) {
+    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) {
+    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) {
+    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) {
+    let weightedZSum = 0;
+    let totalWeight = 0;
+    for (const [key, config] of Object.entries(METABOLIC_PROXY_MARKERS)) {
+        const value = input[key];
+        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) {
+    const c = PHENO_AGE_COEFFICIENTS;
+    const markerCoeffs = [
+        ['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 = 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) {
+    const result = {};
+    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;
+}
+//# sourceMappingURL=pheno-age.js.map

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package/dist/utils.d.ts

@@ -0,0 +1,9 @@
+/**
+ * Clamp a value to a [min, max] range.
+ */
+export declare function clamp(value: number, min: number, max: number): number;
+/**
+ * Natural log with safety floor to avoid -Infinity.
+ */
+export declare function safeLn(value: number, floor?: number): number;
+//# sourceMappingURL=utils.d.ts.map

package/dist/utils.d.ts.map

@@ -0,0 +1 @@
+{"version":3,"file":"utils.d.ts","sourceRoot":"","sources":["../src/utils.ts"],"names":[],"mappings":"AAAA;;GAEG;AACH,wBAAgB,KAAK,CAAC,KAAK,EAAE,MAAM,EAAE,GAAG,EAAE,MAAM,EAAE,GAAG,EAAE,MAAM,GAAG,MAAM,CAErE;AAED;;GAEG;AACH,wBAAgB,MAAM,CAAC,KAAK,EAAE,MAAM,EAAE,KAAK,SAAQ,GAAG,MAAM,CAE3D"}

package/dist/utils.js

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

package/dist/utils.js.map

@@ -0,0 +1 @@
+{"version":3,"file":"utils.js","sourceRoot":"","sources":["../src/utils.ts"],"names":[],"mappings":"AAAA;;GAEG;AACH,MAAM,UAAU,KAAK,CAAC,KAAa,EAAE,GAAW,EAAE,GAAW;IAC3D,OAAO,IAAI,CAAC,GAAG,CAAC,IAAI,CAAC,GAAG,CAAC,KAAK,EAAE,GAAG,CAAC,EAAE,GAAG,CAAC,CAAC;AAC7C,CAAC;AAED;;GAEG;AACH,MAAM,UAAU,MAAM,CAAC,KAAa,EAAE,KAAK,GAAG,KAAK;IACjD,OAAO,IAAI,CAAC,GAAG,CAAC,IAAI,CAAC,GAAG,CAAC,KAAK,EAAE,KAAK,CAAC,CAAC,CAAC;AAC1C,CAAC"}

package/package.json

@@ -1,10 +1,15 @@
 {
   "name": "@ottolab/bio-age",
-  "version": "0.1.0",
+  "version": "0.1.1",
   "license": "MIT",
   "repository": "https://github.com/hokev/Otto",
-  "publishConfig": { "access": "public" },
+  "publishConfig": {
+    "access": "public"
+  },
   "type": "module",
+  "files": [
+    "dist"
+  ],
   "exports": {
     ".": {
       "import": {
@@ -16,6 +21,7 @@
   },
   "scripts": {
     "build": "tsc --build",
+    "prepublishOnly": "npm run build",
     "lint": "eslint src/",
     "test": "vitest run"
   },