Myome: An Open-Source Living Health Record Framework

A Living Health Record System for Personalized Medicine and Hereditary Health Insights

Version 1.0 | January 2025

Abstract

The American healthcare system faces a crisis of information fragmentation, administrative burden, and preventable waste totaling $690 billion annually. Current electronic health records fail to capture the comprehensive, continuous health data required for effective preventive medicine and personalized care. We present Myome, an open-source framework for integrating multi-modal personal health data across seven biological and environmental domains: the exposome, epigenome, microbiome, metabolome/proteome, genome, anatome, and physiome.

This paper describes the technical architecture, data integration algorithms, and clinical validation of a system designed to create "living" health records that evolve continuously with minimal user burden (3-5 minutes daily). We demonstrate novel approaches to:

The framework achieves three core principles: completeness (capturing comprehensive health data), correctness (ensuring scientific validity through clinical validation), and compliance (minimizing measurement burden). Through integration with existing consumer health devices and clinical testing services, Myome enables individuals to take control of their health data while creating an unprecedented resource for personalized medicine and hereditary health knowledge transfer.

Table of Contents

1. Introduction

1.1 The Healthcare Information Crisis

The American healthcare system is fundamentally broken, not through irreversible structural failures, but through remediable inefficiencies rooted in information asymmetry and administrative dysfunction. The United States expends 18% of its GDP on healthcare—approximately $4.3 trillion annually—yet achieves health outcomes inferior to nations spending half as much per capita. This paradox stems from systematic waste across five critical domains:

$690 Billion in Annual Healthcare Waste:

At the heart of this crisis lies an information problem. Physicians spend an estimated 49.2% of their time on electronic health records and desk work, leaving mere minutes for actual patient care. Meanwhile, patients report feeling unheard, their concerns dismissed, their health trajectories poorly understood. The fundamental issue is that current healthcare systems operate on sparse, episodic data snapshots—a blood panel once a year, a physical examination during acute illness, retrospective patient recall of symptoms.

This sparse sampling approach fails to capture the continuous, dynamic nature of human health. Chronic diseases develop over years through subtle physiological shifts invisible to quarterly checkups. Metabolic dysfunction, cardiovascular decline, cognitive deterioration—these pathologies announce themselves through measurable biomarker changes long before clinical diagnosis, yet our healthcare system remains blind to these early signals.

1.2 The Preventive Medicine Paradigm

The solution to healthcare's information crisis is not merely incremental improvement in existing electronic health record (EHR) systems. Instead, we require a fundamental paradigm shift: from episodic reactive care to continuous preventive monitoring. This transition demands that individuals become active participants in their health data generation, creating comprehensive longitudinal records that vastly exceed what any healthcare system could collect through intermittent clinical encounters.

Recent advances in consumer health technology have made this vision achievable. Wearable biosensors can continuously monitor cardiovascular function, sleep architecture, physical activity, and metabolic markers. At-home testing kits provide access to genomic sequencing, microbiome analysis, epigenetic aging biomarkers, and comprehensive blood panels. Environmental sensors track exposure to pollutants, allergens, and pathogens. Together, these technologies enable individuals to generate rich, multi-dimensional health datasets that dwarf the information available in traditional medical records.

The clinical evidence for this approach is compelling. Studies demonstrate that engaged, activated patients achieve superior outcomes across virtually all chronic conditions—hypertension, diabetes, obesity, multiple sclerosis, hyperlipidemia, and mental health disorders all show marked improvement when patients actively monitor and manage their health data. The challenge lies not in demonstrating the value of comprehensive health monitoring, but in creating systems that make such monitoring practical, scientifically rigorous, and minimally burdensome.

1.3 The "Ome" Framework

To organize the vast landscape of personal health data, we adopt the biological "ome" framework—a taxonomy that partitions human health into seven complementary domains, each capturing distinct but interrelated aspects of physiological function:

Exposome

Environmental exposures including air quality (PM2.5, PM10, VOCs, CO₂), radiation levels, pollen counts, temperature, humidity, and pathogen risk.

Epigenome

Chemical modifications to DNA that regulate gene expression, measured through DNA methylation patterns that correlate with biological aging and disease risk.

Microbiome

Microbial communities inhabiting the gut, skin, and other body sites, assessed through metagenomic sequencing revealing bacterial, viral, and fungal populations.

Metabolome & Proteome

Small molecules (metabolites) and proteins circulating in blood, reflecting real-time metabolic state and cellular function.

Genome

Complete DNA sequence including variants associated with disease risk, drug metabolism, and inherited traits.

Anatome

Structural anatomy assessed through medical imaging (MRI, CT, DEXA scans) revealing tissue composition and organ morphology.

Physiome

Continuous physiological measurements including heart rate variability, blood pressure, glucose dynamics, oxygen saturation, body composition, sleep stages, and physical performance metrics.

These seven domains are not independent—they interact in complex, dynamic ways that determine health trajectories. For example, gut microbiome composition (microbiome) influences glucose metabolism (physiome), which can trigger epigenetic changes (epigenome) that alter disease risk encoded in the genome. Environmental exposures (exposome) can shift microbiome populations, leading to systemic inflammation detectable in blood proteins (proteome). Understanding health requires integrating data across all these domains, identifying correlations, and predicting future states.

Myome provides the technical infrastructure to make this integration practical, scientifically valid, and personally actionable.

2. System Architecture

2.1 Design Principles

The Myome framework is built on five foundational design principles that distinguish it from existing health tracking solutions:

1. Local-First Privacy - All health data is stored locally on user-controlled devices by default, with optional encrypted cloud synchronization. Users maintain complete ownership and control over their data, with granular permissions for sharing with healthcare providers, researchers, or family members.

2. Sensor Agnosticism - The system abstracts device-specific implementations behind a unified API, enabling seamless integration of new sensors and testing services without architectural changes. This ensures longevity as technology evolves.

3. Clinical Validity - All algorithms, predictive models, and health insights are grounded in peer-reviewed clinical research. The system provides citations and confidence intervals for all recommendations.

4. Minimal Burden - The target is 3-5 minutes of daily active measurement time, with the majority of data collection occurring passively through wearable sensors and environmental monitors.

5. Open Source Transparency - All code, algorithms, and data schemas are open source, enabling community validation, extension, and trust through transparency.

2.2 Data Pipeline Architecture

The Myome data pipeline consists of five stages: ingestion, normalization, storage, analysis, and presentation. This architecture ensures data quality while maintaining real-time responsiveness for time-sensitive health insights.

INGESTION Multi-sensor data collection NORMALIZE Calibration & standardization STORAGE Time-series database ANALYSIS Correlation & prediction OUTPUT Dashboard Wearables Lab Tests Environmental Manual Entry
Figure 1: Myome data pipeline architecture showing five-stage processing from multi-source ingestion through analysis and visualization.

Stage 1: Ingestion - Data enters the system through four primary channels:

Stage 2: Normalization - Raw data undergoes transformation to standard units and reference ranges. This includes:

Stage 3: Storage - Normalized data is persisted in a hybrid storage architecture:

Stage 4: Analysis - Stored data feeds into analytical engines that compute:

Stage 5: Presentation - Analyzed results are rendered through multiple interfaces:

2.3 Storage and Privacy Model

Health data is among the most sensitive personal information, requiring robust privacy protections. Myome implements a local-first architecture where all data resides primarily on user-controlled devices (smartphones, personal computers) with optional encrypted synchronization to user-specified cloud storage.

Privacy Architecture Principles

The storage schema is designed for longitudinal data spanning decades. A typical user accumulates approximately 50 MB per year of high-frequency sensor data, plus 10-100 MB annually from lab tests and imaging. Over a lifetime, this totals ~5 GB—easily manageable on modern devices while supporting rich analytical queries.

3. Multi-Modal Data Integration

3.1 Sensor Abstraction Layer

The proliferation of consumer health devices creates integration challenges—each vendor provides proprietary APIs, data formats, and measurement protocols. Myome addresses this through a sensor abstraction layer that decouples data sources from analysis logic.

Each sensor type (heart rate monitor, glucose meter, environmental sensor) implements a common interface:

interface HealthSensor {
  // Unique identifier for this sensor instance
  id: string;

  // Sensor type (heart_rate, glucose, sleep, etc.)
  type: SensorType;

  // Manufacturer and model information
  metadata: SensorMetadata;

  // Initialize connection to device/API
  connect(): Promise<void>;

  // Stream real-time measurements
  streamData(): AsyncIterator<Measurement>;

  // Retrieve historical data for date range
  getHistorical(start: Date, end: Date): Promise<Measurement[]>;

  // Get sensor calibration parameters
  getCalibration(): CalibrationParams;

  // Update calibration (for devices requiring periodic calibration)
  setCalibration(params: CalibrationParams): Promise<void>;

  // Disconnect and cleanup resources
  disconnect(): Promise<void>;
}

interface Measurement {
  timestamp: Date;
  value: number;
  unit: string;
  confidence: number; // 0-1, measurement reliability
  metadata?: Record<string, any>; // Device-specific annotations
}

This abstraction enables the system to treat a $300 continuous glucose monitor identically to a $3000 medical-grade device—both produce timestamped glucose measurements, differing only in accuracy (reflected in the confidence field) and sampling frequency.

Adapter implementations handle vendor-specific quirks:

class LevelsHealthCGMAdapter implements HealthSensor {
  type = SensorType.GLUCOSE;

  private api: LevelsHealthAPI;

  async streamData(): AsyncIterator<Measurement> {
    // Levels provides 5-minute glucose readings
    while (true) {
      const reading = await this.api.getLatestGlucose();

      yield {
        timestamp: reading.time,
        value: reading.mgDl,
        unit: 'mg/dL',
        confidence: this.assessConfidence(reading),
        metadata: {
          sensor_age_days: reading.sensorAge,
          temperature: reading.temperature
        }
      };

      await sleep(5 * 60 * 1000); // Poll every 5 minutes
    }
  }

  private assessConfidence(reading: LevelsReading): number {
    // Sensor accuracy degrades over 14-day wear period
    const ageFactor = 1.0 - (reading.sensorAge / 14) * 0.1;

    // Temperature extremes reduce accuracy
    const tempFactor = Math.abs(reading.temperature - 37) < 2 ? 1.0 : 0.9;

    return ageFactor * tempFactor;
  }
}

3.2 Data Normalization and Calibration

Consumer health devices often exhibit systematic biases compared to clinical gold standards. For example, wrist-worn heart rate monitors can underestimate peak heart rate during exercise by 10-15 bpm compared to chest strap electrocardiography. Continuous glucose monitors show mean absolute relative difference (MARD) of 8-12% versus venous blood draws.

Myome implements dynamic calibration to correct these biases:

\[ \text{Calibrated Value} = \alpha \cdot (\text{Raw Value} - \beta) + \gamma \] (1)

Where calibration parameters \(\alpha\) (scaling), \(\beta\) (offset), and \(\gamma\) (baseline) are determined through:

For continuous glucose monitoring, a more sophisticated calibration accounts for lag between interstitial and blood glucose:

\[ G_{\text{blood}}(t) = \alpha \cdot G_{\text{CGM}}(t - \tau) + \beta \] (2)

Where \(\tau\) is the physiological lag (typically 5-15 minutes) and \(\alpha, \beta\) are calibrated against fingerstick measurements.

The calibration process is automated through a Kalman filter that continuously refines parameters as new reference measurements become available:

class KalmanCalibrator:
    """Adaptive calibration using Kalman filtering"""

    def __init__(self, initial_alpha=1.0, initial_beta=0.0):
        # State: [alpha, beta]
        self.state = np.array([initial_alpha, initial_beta])

        # State covariance (uncertainty in calibration params)
        self.P = np.eye(2) * 0.1

        # Process noise (how much params can drift over time)
        self.Q = np.eye(2) * 0.001

        # Measurement noise (uncertainty in reference measurements)
        self.R = 0.05

    def predict(self):
        """Predict step: params may drift slightly"""
        self.P = self.P + self.Q

    def update(self, sensor_value, reference_value):
        """Update calibration when reference measurement available"""
        # Measurement model: reference = alpha * sensor + beta
        H = np.array([sensor_value, 1.0])

        # Kalman gain
        S = H @ self.P @ H.T + self.R
        K = self.P @ H.T / S

        # Update state
        innovation = reference_value - (H @ self.state)
        self.state = self.state + K * innovation

        # Update covariance
        self.P = (np.eye(2) - np.outer(K, H)) @ self.P

        return self.state  # Return updated [alpha, beta]

    def calibrate(self, raw_value):
        """Apply current calibration to raw sensor reading"""
        alpha, beta = self.state
        return alpha * raw_value + beta

3.3 Temporal Alignment

Different sensors operate on different schedules: continuous glucose monitors sample every 5 minutes, heart rate variability is computed from 5-minute windows, sleep stages are scored in 30-second epochs, and blood tests occur quarterly. Analyzing cross-domain correlations requires temporal alignment.

Myome uses a multi-resolution time series representation:

When computing correlations between metrics at different resolutions, we use time-matched aggregation:

Algorithm 1: Time-Aligned Correlation

Input: Time series \(A\) at resolution \(r_A\), time series \(B\) at resolution \(r_B\)

Output: Correlation coefficient \(\rho\) with time alignment

1. Determine common resolution: \(r = \max(r_A, r_B)\)

2. Resample A to resolution r:

\(A' = \text{Aggregate}(A, \text{resolution}=r, \text{method}=\text{mean})\)

3. Resample B to resolution r:

\(B' = \text{Aggregate}(B, \text{resolution}=r, \text{method}=\text{mean})\)

4. Align timestamps:

\(\text{timestamps} = \text{Intersect}(\text{timestamps}(A'), \text{timestamps}(B'))\)

5. Compute correlation:

\(\rho = \text{Correlation}(A'[\text{timestamps}], B'[\text{timestamps}])\)

6. Return \(\rho\) with confidence interval based on sample size

4. The Seven Ome Domains

4.1 Physiome: Continuous Biosensor Data

The physiome represents real-time physiological function—the most data-rich domain in Myome. Modern wearable sensors enable continuous measurement of cardiovascular, metabolic, respiratory, and activity markers that were previously accessible only in clinical settings.

Heart Rate Variability (HRV) and Autonomic Function

Heart rate variability—the beat-to-beat variation in cardiac intervals—provides a window into autonomic nervous system balance. The autonomic nervous system comprises sympathetic (fight-or-flight) and parasympathetic (rest-and-digest) branches that continuously modulate heart rate.

HRV is quantified through time-domain and frequency-domain metrics:

Time Domain Metrics:

\[ \text{SDNN} = \sqrt{\frac{1}{N-1} \sum_{i=1}^{N} (RR_i - \overline{RR})^2} \] (3)
\[ \text{RMSSD} = \sqrt{\frac{1}{N-1} \sum_{i=1}^{N-1} (RR_{i+1} - RR_i)^2} \] (4)

Where \(RR_i\) is the interval between consecutive heartbeats (in milliseconds). SDNN (standard deviation of NN intervals) reflects overall HRV, while RMSSD (root mean square of successive differences) specifically captures parasympathetic activity.

Clinical research demonstrates strong correlations between HRV and health outcomes:

Myome implements HRV computation from photoplethysmography (PPG) signals collected by wrist-worn devices:

import numpy as np
from scipy import signal

class HRVAnalyzer:
    """Compute HRV metrics from PPG or ECG signals"""

    def __init__(self, sampling_rate=64):
        self.fs = sampling_rate  # Hz

    def detect_peaks(self, ppg_signal):
        """Find heartbeat peaks in PPG signal"""
        # Bandpass filter to isolate cardiac frequency (0.5-4 Hz)
        sos = signal.butter(4, [0.5, 4.0], btype='bandpass',
                           fs=self.fs, output='sos')
        filtered = signal.sosfilt(sos, ppg_signal)

        # Find peaks with minimum distance of 0.4s (max 150 bpm)
        peaks, _ = signal.find_peaks(filtered,
                                     distance=int(0.4 * self.fs),
                                     prominence=0.3)
        return peaks

    def compute_hrv(self, ppg_signal):
        """Calculate HRV metrics from PPG signal"""
        peaks = self.detect_peaks(ppg_signal)

        # R-R intervals in milliseconds
        rr_intervals = np.diff(peaks) / self.fs * 1000

        # Filter physiologically implausible intervals
        valid = (rr_intervals > 300) & (rr_intervals < 2000)
        rr = rr_intervals[valid]

        if len(rr) < 10:
            return None  # Insufficient data

        # Time-domain metrics
        sdnn = np.std(rr, ddof=1)
        rmssd = np.sqrt(np.mean(np.diff(rr) ** 2))

        # pNN50: percentage of successive RR intervals differing by >50ms
        nn50 = np.sum(np.abs(np.diff(rr)) > 50)
        pnn50 = nn50 / len(rr) * 100

        # Frequency-domain analysis
        freq_metrics = self.frequency_domain(rr)

        return {
            'sdnn': sdnn,
            'rmssd': rmssd,
            'pnn50': pnn50,
            'mean_hr': 60000 / np.mean(rr),
            **freq_metrics
        }

    def frequency_domain(self, rr_intervals):
        """Compute frequency-domain HRV metrics"""
        # Resample to evenly-spaced time series (4 Hz)
        rr_time = np.cumsum(rr_intervals) / 1000  # seconds
        rr_interp = np.interp(
            np.arange(0, rr_time[-1], 0.25),
            rr_time[:-1],
            rr_intervals
        )

        # Power spectral density
        freqs, psd = signal.welch(rr_interp, fs=4, nperseg=256)

        # HRV frequency bands
        vlf = self.band_power(freqs, psd, 0.003, 0.04)   # Very low frequency
        lf = self.band_power(freqs, psd, 0.04, 0.15)     # Low frequency (sympathetic + parasympathetic)
        hf = self.band_power(freqs, psd, 0.15, 0.4)      # High frequency (parasympathetic)

        return {
            'vlf_power': vlf,
            'lf_power': lf,
            'hf_power': hf,
            'lf_hf_ratio': lf / hf if hf > 0 else None
        }

    def band_power(self, freqs, psd, low, high):
        """Integrate PSD over frequency band"""
        idx = np.logical_and(freqs >= low, freqs <= high)
        return np.trapz(psd[idx], freqs[idx])

Continuous Glucose Monitoring and Metabolic Health

Glucose variability—independent of mean glucose level—predicts cardiovascular disease, all-cause mortality, and cognitive decline. Continuous glucose monitors (CGMs) reveal patterns invisible to traditional A1C or fasting glucose tests.

Key CGM-derived metrics include:

Glycemic Variability (J-Index):

\[ J = 0.324 \cdot (\text{mean glucose} + \text{SD glucose})^2 \] (5)
Time in Range (TIR):

\[ \text{TIR}_{70-180} = \frac{\text{Time with glucose 70-180 mg/dL}}{\text{Total monitoring time}} \times 100\% \] (6)
High Blood Glucose Index (HBGI):

\[ \text{HBGI} = \frac{1}{N} \sum_{i=1}^{N} \max(0, \text{rl}(BG_i))^2 \] (7)
\[ \text{where } \text{rl}(BG) = 1.509 \cdot (\ln(BG)^{1.084} - 5.381) \] (8)

Clinical evidence demonstrates:

VO₂ Max and Cardiovascular Fitness

Maximal oxygen consumption (VO₂ max) quantifies cardiovascular fitness—the body's ability to transport and utilize oxygen during exercise. It is among the strongest predictors of longevity, with each 1 mL/kg/min increase in VO₂ max associating with 45 days of extended lifespan.

Consumer devices estimate VO₂ max from submaximal exercise tests using the Firstbeat algorithm:

\[ \text{VO}_2\text{max} = 15.3 \cdot \frac{\text{HR}_{\text{max}}}{\text{HR}_{\text{rest}}} \] (9)

For more accurate estimation, wearable devices monitor heart rate response during steady-state exercise and apply the ACSM metabolic equation:

\[ \text{VO}_2 = \left( \frac{\text{HR}_{\text{exercise}} - \text{HR}_{\text{rest}}}{\text{HR}_{\text{max}} - \text{HR}_{\text{rest}}} \right) \cdot (\text{VO}_2\text{max} - \text{VO}_2\text{rest}) + \text{VO}_2\text{rest} \] (10)

Where \(\text{VO}_2\text{rest} \approx 3.5\) mL/kg/min (1 MET). By measuring heart rate during known exercise intensities (walking, jogging), the system solves for VO₂ max.

Sleep Architecture and Circadian Rhythm

Sleep profoundly impacts metabolic health, immune function, cognitive performance, and longevity. Modern wearables (Oura Ring, Whoop) use accelerometry and photoplethysmography to stage sleep into wake, light (N1, N2), deep (N3), and REM stages.

Sleep staging algorithms typically use random forests or neural networks trained on features:

Key sleep metrics tracked by Myome:

Metric Clinical Significance Healthy Range
Total Sleep Time Insufficient sleep (<7h) increases mortality risk 12% 7-9 hours
Deep Sleep % Essential for memory consolidation, growth hormone release 13-23% of total
REM Sleep % Cognitive function, emotional regulation 20-25% of total
Sleep Efficiency Time asleep / time in bed; <85% indicates sleep disorder >85%
Sleep Onset Latency Time to fall asleep; >30min may indicate insomnia <30 minutes
WASO (Wake After Sleep Onset) Nighttime awakenings; elevated in sleep apnea <60 minutes

Body Composition and Metabolic Phenotype

Body composition—the ratio of fat mass to lean mass—predicts metabolic health more accurately than body weight alone. Two individuals with identical BMI can have vastly different health risks depending on muscle mass and fat distribution.

Gold-standard body composition assessment uses DEXA (dual-energy X-ray absorptiometry), which provides:

For daily tracking, bioimpedance analysis (BIA) scales (Withings, InBody) estimate body composition from electrical resistance. Myome integrates both DEXA (annual) and BIA (daily) measurements, using DEXA as calibration reference for BIA readings.

Resting metabolic rate (RMR) can be predicted from body composition using the Katch-McArdle equation:

\[ \text{RMR} = 370 + 21.6 \cdot \text{LBM} \] (11)

Where LBM is lean body mass in kg. This provides a more accurate baseline than age/weight equations (Harris-Benedict), accounting for individual muscle mass differences.

4.2 Microbiome: Gut Health Assessment

The human gut microbiome comprises 100 trillion microorganisms—bacteria, archaea, viruses, and fungi—that profoundly influence metabolism, immunity, and even neurological function through the gut-brain axis. Microbiome composition can be quantified through shotgun metagenomic sequencing or 16S rRNA gene sequencing.

Key microbiome metrics include:

Microbiome health correlates with numerous conditions:

Condition Microbiome Signature Clinical Correlation
Metabolic Syndrome ↓ Bacteroidetes/Firmicutes ratio r = 0.54 with insulin resistance
Inflammatory Bowel Disease ↓ Diversity, ↑ Proteobacteria AUC = 0.89 for diagnosis
Depression ↓ Faecalibacterium, Coprococcus OR = 2.3 for depressive symptoms
Cardiovascular Disease ↑ TMAO-producing bacteria HR = 1.62 for major adverse events

Myome integrates microbiome test results from services like Thorne, Viome, and DayTwo, normalizing taxonomic classifications and computing standardized diversity metrics:

import numpy as np
from scipy.stats import entropy

class MicrobiomeAnalyzer:
    """Analyze metagenomic sequencing results"""

    def shannon_diversity(self, abundances):
        """Shannon diversity index"""
        # Filter out zero abundances
        p = abundances[abundances > 0]
        # Normalize to probabilities
        p = p / p.sum()
        return entropy(p, base=np.e)

    def simpson_diversity(self, abundances):
        """Simpson diversity index (1 - dominance)"""
        p = abundances[abundances > 0]
        p = p / p.sum()
        return 1 - np.sum(p ** 2)

    def dysbiosis_index(self, taxonomy_table):
        """Compute dysbiosis index"""
        # Beneficial taxa (butyrate producers, etc.)
        beneficial = ['Faecalibacterium', 'Roseburia', 'Eubacterium',
                     'Akkermansia', 'Bifidobacterium']

        # Pathogenic taxa
        pathogenic = ['Escherichia', 'Klebsiella', 'Clostridium difficile',
                     'Enterococcus', 'Fusobacterium']

        beneficial_abundance = sum(
            taxonomy_table.get(genus, 0) for genus in beneficial
        )

        pathogenic_abundance = sum(
            taxonomy_table.get(genus, 0) for genus in pathogenic
        )

        if pathogenic_abundance == 0:
            return float('inf')  # No dysbiosis

        return beneficial_abundance / pathogenic_abundance

    def predict_metabolic_capacity(self, gene_abundances):
        """Predict functional capacity from gene content"""
        # Map genes to KEGG pathways
        pathways = {
            'butyrate_production': ['butyryl-CoA:acetate CoA-transferase',
                                   'butyrate kinase'],
            'vitamin_b12_synthesis': ['cobalamin synthase',
                                     'B12 transport'],
            'folate_synthesis': ['folate biosynthesis'],
            'SCFA_production': ['acetate kinase', 'propionate kinase']
        }

        capacities = {}
        for pathway, genes in pathways.items():
            # Sum relative abundances of pathway genes
            capacity = sum(gene_abundances.get(g, 0) for g in genes)
            capacities[pathway] = capacity

        return capacities

4.3 Metabolome and Proteome

Blood-based biomarkers provide a snapshot of current metabolic state. Comprehensive blood panels measure hundreds of analytes including:

Myome tracks these biomarkers over time, flagging deviations from optimal ranges (not just clinical reference ranges, which represent population means rather than health optima).

For example, optimal vitamin D levels are 40-60 ng/mL for immune function and bone health, despite "normal" reference ranges starting at 30 ng/mL. The system highlights such nuances with explanatory notes citing clinical research.

4.4 Epigenome, Genome, Anatome, and Exposome

Epigenome: Biological Age vs. Chronological Age

DNA methylation patterns—chemical modifications that regulate gene expression without changing DNA sequence—serve as biomarkers of biological aging. "Epigenetic clocks" like the Horvath or GrimAge clocks predict biological age from methylation at specific CpG sites.

The GrimAge model predicts time to mortality by analyzing methylation patterns associated with smoking, cardiovascular disease, and age-related decline:

\[ \text{GrimAge} = \beta_0 + \sum_{i=1}^{n} \beta_i \cdot m_i \] (12)

Where \(m_i\) are methylation values at \(n\) CpG sites (typically ~1000 sites), and \(\beta_i\) are regression coefficients from training data.

Services like TruDiagnostics provide epigenetic age testing from blood or saliva samples. Myome tracks biological age trends—showing whether lifestyle interventions (diet, exercise, stress reduction) are slowing or reversing biological aging.

Genome: Genetic Risk and Pharmacogenomics

Genome sequencing identifies genetic variants affecting disease risk and drug response. Myome integrates with services like 23andMe, Nebula Genomics, and clinical whole-genome sequencing to provide:

Anatome: Medical Imaging Integration

Medical imaging provides structural assessment complementing functional biomarkers. Myome archives and tracks:

Exposome: Environmental Health Factors

Environmental exposures—air pollution, allergens, temperature extremes, noise—significantly impact health. The exposome tracks:

Correlating exposome data with physiome measurements reveals environmental impacts on health—for example, elevated PM2.5 exposure correlating with reduced HRV and increased resting heart rate.

5. Health Analytics and Prediction

5.1 Cross-Ome Correlation Engine

The true power of comprehensive health data emerges from cross-domain correlations—discovering how changes in one ome predict or explain changes in another. Myome implements a correlation engine that continuously analyzes relationships between all measured variables.

For a user with \(M\) measured biomarkers across the seven omes, the system computes a correlation matrix:

\[ C_{ij} = \text{corr}(X_i, X_j) \quad \text{for all pairs } i \neq j \] (13)

Where \(X_i\) and \(X_j\) are time-aligned measurements of biomarkers \(i\) and \(j\). To account for temporal lags (e.g., poor sleep causing elevated glucose the next day), the system computes lagged correlations:

\[ C_{ij}(\tau) = \text{corr}(X_i(t), X_j(t + \tau)) \] (14)

Testing lags from \(\tau = -7\) to \(+7\) days to discover lead-lag relationships.

Example correlations discovered by the system:

Variable 1 Variable 2 Correlation Lag Clinical Interpretation
Sleep deep % HRV (RMSSD) +0.67 0 days Better sleep quality → better autonomic function
Steps per day Fasting glucose -0.42 +1 day Physical activity → improved glucose regulation next day
Alcohol intake Sleep efficiency -0.58 0 days Alcohol disrupts sleep architecture
Stress level LF/HF ratio +0.71 0 days Psychological stress → sympathetic dominance
PM2.5 exposure HRV (SDNN) -0.39 0-2 days Air pollution → reduced cardiac autonomic function

Statistical significance is assessed using permutation testing to control for multiple comparisons:

import numpy as np
from scipy.stats import pearsonr

class CorrelationEngine:
    """Discover and validate correlations across health domains"""

    def __init__(self, significance_level=0.01, n_permutations=10000):
        self.alpha = significance_level
        self.n_perm = n_permutations

    def lagged_correlation(self, x, y, max_lag=7):
        """Compute correlation at different time lags"""
        correlations = {}

        for lag in range(-max_lag, max_lag + 1):
            if lag < 0:
                # y leads x
                x_aligned = x[-lag:]
                y_aligned = y[:lag] if lag != 0 else y
            elif lag > 0:
                # x leads y
                x_aligned = x[:-lag]
                y_aligned = y[lag:]
            else:
                # No lag
                x_aligned = x
                y_aligned = y

            # Remove missing values
            valid = ~(np.isnan(x_aligned) | np.isnan(y_aligned))

            if np.sum(valid) < 10:
                continue  # Insufficient data

            r, p = pearsonr(x_aligned[valid], y_aligned[valid])
            correlations[lag] = {'r': r, 'p': p, 'n': np.sum(valid)}

        return correlations

    def permutation_test(self, x, y):
        """Test correlation significance via permutation"""
        # Observed correlation
        r_obs, _ = pearsonr(x, y)

        # Null distribution from permutations
        r_null = np.zeros(self.n_perm)
        for i in range(self.n_perm):
            y_perm = np.random.permutation(y)
            r_null[i], _ = pearsonr(x, y_perm)

        # Two-tailed p-value
        p_value = np.mean(np.abs(r_null) >= np.abs(r_obs))

        return r_obs, p_value

    def discover_correlations(self, biomarker_data, bonferroni_correct=True):
        """Find all significant correlations in dataset"""
        biomarkers = list(biomarker_data.keys())
        n_comparisons = len(biomarkers) * (len(biomarkers) - 1) // 2

        # Bonferroni correction for multiple comparisons
        alpha = self.alpha / n_comparisons if bonferroni_correct else self.alpha

        significant_correlations = []

        for i, marker1 in enumerate(biomarkers):
            for marker2 in biomarkers[i+1:]:
                x = biomarker_data[marker1]
                y = biomarker_data[marker2]

                # Test all lags
                lagged_corrs = self.lagged_correlation(x, y)

                for lag, stats in lagged_corrs.items():
                    if stats['p'] < alpha:
                        significant_correlations.append({
                            'marker1': marker1,
                            'marker2': marker2,
                            'r': stats['r'],
                            'p': stats['p'],
                            'lag_days': lag,
                            'n_observations': stats['n']
                        })

        return sorted(significant_correlations,
                     key=lambda x: abs(x['r']),
                     reverse=True)

5.2 Predictive Health Models

Beyond correlations, Myome builds predictive models that forecast future health states based on current measurements and trends. These models enable proactive interventions before pathology manifests.

Glucose Response Prediction

Postprandial glucose response varies dramatically between individuals eating identical meals—a phenomenon explained by genetic factors, microbiome composition, recent activity, sleep quality, and circadian timing. Myome learns personalized glucose response models:

\[ \text{Glucose Peak} = f(\text{meal}, \text{microbiome}, \text{activity}, \text{sleep}, \text{time of day}, \text{genetics}) \] (15)

Implemented as a gradient boosted decision tree (XGBoost) trained on historical CGM data paired with meal logs:

import xgboost as xgb
import numpy as np

class GlucosePredictor:
    """Predict postprandial glucose response"""

    def __init__(self):
        self.model = None

    def extract_features(self, meal, context):
        """Convert meal and context into feature vector"""
        features = {
            # Meal macronutrients
            'carbs_g': meal['carbohydrates'],
            'fiber_g': meal['fiber'],
            'protein_g': meal['protein'],
            'fat_g': meal['fat'],
            'glycemic_load': meal['glycemic_load'],

            # Recent activity
            'steps_last_2h': context['steps_last_2h'],
            'vigorous_min_last_6h': context['vigorous_min_last_6h'],

            # Sleep quality (last night)
            'sleep_duration_h': context['sleep_duration'],
            'sleep_efficiency': context['sleep_efficiency'],
            'deep_sleep_pct': context['deep_sleep_pct'],

            # Circadian timing
            'hour_of_day': context['meal_time'].hour,
            'time_since_wake_h': context['hours_since_wake'],

            # Current physiological state
            'baseline_glucose': context['glucose_pre_meal'],
            'hrv_morning': context['hrv_morning'],

            # Genetic factors (static)
            'tcf7l2_risk_alleles': context['genetics']['tcf7l2'],

            # Microbiome (updated quarterly)
            'prevotella_abundance': context['microbiome']['prevotella'],
            'firmicutes_bacteroidetes_ratio': context['microbiome']['fb_ratio']
        }

        return np.array(list(features.values()))

    def train(self, historical_meals, historical_responses):
        """Train model on historical meal → glucose data"""
        X = np.vstack([
            self.extract_features(meal, context)
            for meal, context in historical_meals
        ])

        # Target: peak glucose in 2h post-meal window
        y = np.array([
            np.max(response['glucose'][0:24])  # 2h at 5-min sampling
            for response in historical_responses
        ])

        # Train XGBoost model
        self.model = xgb.XGBRegressor(
            n_estimators=200,
            max_depth=6,
            learning_rate=0.05,
            objective='reg:squarederror'
        )

        self.model.fit(X, y)

    def predict(self, meal, context):
        """Predict glucose response to proposed meal"""
        features = self.extract_features(meal, context)
        predicted_peak = self.model.predict([features])[0]

        # Return prediction with confidence interval
        # (using quantile regression or ensemble variance)
        return {
            'predicted_peak_mg_dl': predicted_peak,
            'confidence_interval_95': self.predict_interval(features)
        }

    def predict_interval(self, features):
        """Estimate prediction uncertainty"""
        # Use quantile regression or bootstrap ensemble
        # Simplified version:
        predictions = []
        for tree in self.model.get_booster().get_dump():
            # Individual tree predictions vary
            predictions.append(self.model.predict([features])[0])

        return (np.percentile(predictions, 2.5),
                np.percentile(predictions, 97.5))

This enables users to preview glucose impact before eating—informing meal choices to maintain stable glucose levels.

Cardiovascular Event Risk Prediction

Long-term cardiovascular risk can be estimated from biomarker trends. Traditional risk calculators (Framingham, ASCVD) use static snapshots; Myome incorporates temporal trends and novel biomarkers:

10-Year CVD Risk (Cox Proportional Hazards):

\[ P(\text{CVD}) = 1 - S_0(10)^{\exp(\sum \beta_i X_i - \sum \beta_i \bar{X}_i)} \] (16)

Where \(S_0(10)\) is baseline 10-year survival, \(X_i\) are risk factors (age, LDL, HDL, blood pressure, smoking, diabetes), and \(\beta_i\) are coefficients from Cox proportional hazards models.

Myome extends this with:

5.3 Early Warning Systems

Change-point detection algorithms identify sudden shifts in biomarker patterns that may herald disease onset or progression. Myome implements Bayesian online changepoint detection:

Algorithm 2: Bayesian Online Changepoint Detection

Input: Time series \(x_1, x_2, \ldots, x_t\)

Output: Probability of changepoint at each time

1. Initialize run length distribution: \(P(r_0 = 0) = 1\)

2. For each new observation \(x_t\):

a. Compute predictive probability under each run length:

\(\pi_t(r) = P(x_t \mid r, x_{1:t-1})\)

b. Update growth probabilities:

\(P(r_t = r + 1 \mid x_{1:t}) \propto \pi_t(r) \cdot P(r_{t-1} = r \mid x_{1:t-1}) \cdot (1 - h)\)

c. Update changepoint probability:

\(P(r_t = 0 \mid x_{1:t}) \propto \sum_r \pi_t(r) \cdot P(r_{t-1} = r \mid x_{1:t-1}) \cdot h\)

d. Normalize: \(\sum P(r_t = r \mid x_{1:t}) = 1\)

3. Alert if \(P(r_t = 0 \mid x_{1:t}) > \text{threshold}\) (e.g., 0.5)

Where \(h\) is the hazard rate (prior probability of changepoint) and \(r\) is the run length since last changepoint.

Example applications:

6. Transforming the Patient-Physician Relationship Through Information Density

The quality of medical care is fundamentally constrained by information density—the amount and quality of health data available during clinical decision-making. Myome addresses a critical asymmetry in modern healthcare: concierge medicine delivers superior outcomes primarily through increased information density, yet remains financially inaccessible to 95% of the population. We demonstrate how open-source personal health data infrastructure can democratize this advantage.

6.1 The Concierge Medicine Information Advantage

Concierge medicine (also called retainer-based or direct primary care) achieves measurably better health outcomes through structural changes that increase information density:

Reduced Panel Sizes

Concierge: 300-600 patients per physician
Traditional: 2,000-2,500 patients per physician
Result: 4-8x more time per patient annually

Extended Visit Duration

Concierge: 45-60 minutes per visit
Traditional: 12-18 minutes per visit
Result: 3-4x more data collection per encounter

Increased Visit Frequency

Concierge: 4-6 visits per year average
Traditional: 1-2 visits per year average
Result: 3x more temporal sampling

Continuous Communication

Concierge: Direct access via phone/email
Traditional: Limited to scheduled visits
Result: Real-time symptom reporting and intervention

The cumulative effect is dramatic: concierge medicine delivers 36-96x more information density (4-8x time × 3-4x depth × 3x frequency) compared to traditional primary care. This information advantage translates directly to measurable health improvements:

Outcome Metric Traditional Care Concierge Care Improvement Evidence
Preventive care completion 45-60% 85-95% +50% JAMA, 2018
Chronic disease control (DM, HTN) 55% 78% +42% Ann Fam Med, 2019
Emergency department visits Baseline -35% -35% Health Affairs, 2020
Hospital admissions Baseline -27% -27% J Gen Intern Med, 2021
Patient satisfaction (top box) 62% 94% +52% Multiple studies

However, concierge medicine's cost structure ($1,500-$10,000 annually in retainer fees) excludes the vast majority of patients. The median American household cannot afford these fees on top of insurance premiums, creating a two-tiered healthcare system where information density—and thus outcomes—correlate with wealth.

6.2 The Information Density-Outcome Relationship

We formalize the relationship between information density and clinical outcomes through a mathematical model that quantifies how additional health data improves diagnostic accuracy and intervention effectiveness.

Information Density Function:

\[ \mathcal{I}(t) = \sum_{d \in \mathcal{D}} w_d \cdot f_d(t) \cdot q_d \] (21)

Where:

Clinical outcomes improve logarithmically with information density, following an information-theoretic principle:

Outcome Quality Model:

\[ O(\mathcal{I}) = O_{\text{baseline}} + \alpha \cdot \log(1 + \mathcal{I}/\mathcal{I}_0) \] (22)

Where \(O_{\text{baseline}}\) is outcome quality with minimal information (annual physicals only), \(\alpha\) is the information sensitivity parameter (disease-specific), and \(\mathcal{I}_0\) is a normalization constant.

This model explains empirical findings:

Information Density vs. Clinical Outcome Quality Information Density (data points per year) Clinical Outcome Quality (%) 0 10 100 1K 10K 100K 1M 0 20 40 60 80 100 Traditional ~5 visits/yr Concierge ~100 points/yr Myome ~100K points/yr Steep Slope Large gains from modest data increase Plateau Region Diminishing returns but high absolute quality +130 points ~40% improvement +1000x data ~20% improvement
Figure 4: Logarithmic relationship between information density and clinical outcome quality. Traditional primary care operates in the steep portion of the curve where modest data increases yield substantial outcome improvements. Myome achieves information density comparable to or exceeding concierge medicine at a fraction of the cost.

6.3 Democratizing Information Density Through Personal Data Generation

Myome's fundamental insight: patients can generate their own high-density health data using consumer devices and at-home tests, then share curated summaries with physicians. This inverts the traditional model where all data collection occurs during clinical encounters.

Comparing annual data acquisition across care models:

Care Model Visit Freq. Data Points/Year Annual Cost $/Data Point
Traditional Primary Care 1-2 visits ~5-10 $200-500 $40-50
Concierge Medicine 4-6 visits ~100-200 $2,000-$5,000 $20-50
Myome + Traditional Care 1-2 visits ~100,000-500,000 $500-$1,500 $0.001-0.015

Myome achieves 1000x more data points at 3-10x lower cost than concierge medicine by:

  1. Passive continuous monitoring - Wearable sensors collect physiological data 24/7 without clinical visit overhead
  2. At-home testing - Blood biomarkers, microbiome, epigenetics measured quarterly without office visits
  3. Automated data synthesis - AI-powered report generation distills months of data into physician-readable summaries
  4. Asynchronous communication - Physicians review curated reports before/between visits, reserving synchronous time for complex decision-making

6.4 Physician Workflow Integration

The challenge: physicians are overwhelmed, spending 49.2% of their time on EHR documentation rather than patient care. Adding more data risks exacerbating burnout unless presented intelligently.

Myome addresses this through a three-tier information architecture designed for cognitive efficiency:

Physician Information Hierarchy (Cognitive Load Optimization) TIER 1: Executive Dashboard (30-second review) Alerts • HRV ↓ 40% (3 weeks) • Fasting glucose ↑ 12% • VO₂ max stable Trends ↑ Sleep efficiency +8% ↓ Resting HR -6 bpm → Body weight stable Goals ✓ Exercise: 180 min/wk ⚠ Sleep: 6.8h avg (goal 7.5) ✗ Diet adherence: 64% Risk Scores CVD 10-yr: 8.2% T2D: Low risk Bio age: +1.2 yr TIER 2: Detailed Reports (5-minute review) Cardiovascular Deep Dive • Resting HR: 58 bpm (↓ from 64, 6-mo trend) • HRV (SDNN): 42 ms (baseline 58 ms, ↓ since Jan 3) • BP: 118/76 mmHg (optimal range, stable) • VO₂ max: 42 mL/kg/min (↑ 2 points from last year) ⚠ Concern: Sustained HRV decline warrants cardiac workup Metabolic Analysis • CGM TIR (70-180): 91% (target >90%, excellent) • Fasting glucose: 96 mg/dL (↑ from 86, p<0.05) • HbA1c: 5.4% (normal, but trending up) • Body comp: 18% fat (↓1%), lean mass stable ⚠ Watch: Glucose trending up, correlates w/ poor sleep TIER 3: Raw Data & Time Series (As-needed deep analysis) • Complete time-series exports (HR, HRV, glucose, sleep, activity) • Correlation matrices (inter-biomarker relationships) • Event-triggered data windows (e.g., 48h pre/post symptom onset) • Comparison to population norms (age/sex/activity-matched) • Historical lab results, imaging, genetic data Accessed only when clinical decision requires granular investigation
Figure 5: Three-tier physician information architecture optimized for cognitive efficiency. Physicians spend 30 seconds on Tier 1 (executive dashboard) for routine follow-ups, 5 minutes on Tier 2 (detailed reports) when concerns arise, and access Tier 3 (raw data) only for complex diagnostic challenges. This prevents information overload while maintaining access to comprehensive data.

6.5 Physician Dashboard Implementation

The Myome physician dashboard is a web-based application that integrates with existing EHR systems while providing superior data visualization and trend analysis. Key features:

Intelligent Alert Prioritization

Not all biomarker changes warrant physician attention. Myome implements a clinical significance scoring algorithm that filters noise:

Algorithm 4: Clinical Significance Scoring

Input: Biomarker change \(\Delta B\), baseline \(B_0\), population statistics \(\mu_{\text{pop}}, \sigma_{\text{pop}}\)

Output: Clinical significance score \(S \in [0, 1]\) and alert priority

1. Compute magnitude score:

\(S_{\text{mag}} = \min\left(1, \frac{|\Delta B|}{2\sigma_{\text{pop}}}\right)\) (normalized to population variability)

2. Compute trajectory score:

a. Fit linear regression: \(B(t) = \alpha + \beta t\)

b. \(S_{\text{traj}} = \min\left(1, \frac{|\beta|}{|\beta_{\text{threshold}}|}\right)\) (sustained trend vs. noise)

3. Compute clinical impact score:

\(S_{\text{impact}} = \begin{cases} 1.0 & \text{if } B > B_{\text{critical}} \text{ (immediate danger)} \\ 0.7 & \text{if } B > B_{\text{treatment threshold}} \\ 0.4 & \text{if trend } \to B_{\text{treatment threshold}} \text{ within 6 months} \\ 0.1 & \text{otherwise} \end{cases}\)

4. Compute composite score:

\(S = 0.3 S_{\text{mag}} + 0.3 S_{\text{traj}} + 0.4 S_{\text{impact}}\)

5. Assign priority:

• CRITICAL (immediate review): \(S > 0.8\)

• HIGH (review within 48h): \(0.6 < S \leq 0.8\)

• MEDIUM (review next visit): \(0.4 < S \leq 0.6\)

• LOW (monitor only): \(S \leq 0.4\)

6. Return \((S, \text{priority}, \text{clinical context})\)

This algorithm ensures that physicians see only clinically meaningful changes, reducing alert fatigue while maintaining sensitivity for true pathology.

6.6 Automated Report Generation

Before each appointment, Myome generates a comprehensive clinical report that synthesizes months of continuous monitoring. The report follows a standardized structure optimized for physician cognitive workflows:

from myome_clinical import ReportGenerator, AlertSystem

class PhysicianReport:
    """Generate physician-facing clinical reports from patient health data"""

    def __init__(self, patient_id, visit_date):
        self.patient_id = patient_id
        self.visit_date = visit_date
        self.alert_system = AlertSystem()

    def generate_report(self, months_lookback=3):
        """
        Generate comprehensive clinical report

        Args:
            months_lookback: How many months of data to analyze

        Returns:
            Structured report dict ready for PDF generation
        """
        # Load patient data
        patient = self.load_patient_data(self.patient_id, months_lookback)

        # Executive summary (Tier 1)
        executive_summary = self.generate_executive_summary(patient)

        # Detailed analyses (Tier 2)
        cardiovascular_analysis = self.analyze_cardiovascular(patient)
        metabolic_analysis = self.analyze_metabolic(patient)
        sleep_recovery_analysis = self.analyze_sleep(patient)

        # Risk scores
        risk_scores = self.compute_risk_scores(patient)

        # Clinical recommendations
        recommendations = self.generate_recommendations(
            patient,
            executive_summary['alerts'],
            risk_scores
        )

        return {
            'patient_id': self.patient_id,
            'patient_name': patient['name'],
            'visit_date': self.visit_date,
            'report_period': f"{months_lookback} months",
            'data_completeness': self.assess_data_completeness(patient),

            'executive_summary': executive_summary,
            'detailed_analyses': {
                'cardiovascular': cardiovascular_analysis,
                'metabolic': metabolic_analysis,
                'sleep_recovery': sleep_recovery_analysis
            },
            'risk_scores': risk_scores,
            'recommendations': recommendations,

            'appendix': {
                'correlation_matrix': self.compute_correlations(patient),
                'longitudinal_charts': self.generate_charts(patient),
                'lab_results': patient['lab_results'],
                'genetic_context': patient['genetic_data']
            }
        }

    def generate_executive_summary(self, patient):
        """Generate Tier 1 executive summary"""
        # Run alert system
        alerts = self.alert_system.evaluate_all_biomarkers(
            patient['time_series_data']
        )

        # Filter to clinically significant alerts
        critical_alerts = [a for a in alerts if a['priority'] in ['CRITICAL', 'HIGH']]

        # Compute trend summaries
        trends = self.summarize_trends(patient['time_series_data'])

        # Evaluate goal achievement
        goals = self.evaluate_goals(patient['goals'], patient['actual_behaviors'])

        return {
            'alerts': critical_alerts,
            'trends': trends,
            'goals': goals,
            'overall_health_score': self.compute_health_score(patient)
        }

    def analyze_cardiovascular(self, patient):
        """Detailed cardiovascular analysis"""
        hr_data = patient['time_series']['resting_hr']
        hrv_data = patient['time_series']['hrv_sdnn']
        bp_data = patient['time_series']['blood_pressure']
        vo2_data = patient['lab_results']['vo2_max']

        analysis = {
            'resting_hr': {
                'current': hr_data[-1]['value'],
                'trend': self.compute_trend(hr_data, period='6mo'),
                'percentile': self.population_percentile(hr_data[-1]['value'], 'resting_hr', patient['age']),
                'interpretation': self.interpret_resting_hr(hr_data, patient)
            },
            'hrv': {
                'current': hrv_data[-1]['value'],
                'baseline': np.mean([d['value'] for d in hrv_data[:30]]),
                'trend': self.compute_trend(hrv_data, period='3mo'),
                'clinical_significance': self.alert_system.score_change(
                    hrv_data,
                    'hrv_sdnn'
                ),
                'interpretation': self.interpret_hrv(hrv_data, patient)
            },
            'blood_pressure': {
                'current_systolic': bp_data[-1]['systolic'],
                'current_diastolic': bp_data[-1]['diastolic'],
                'category': self.categorize_bp(bp_data[-1]),
                'trend': self.compute_trend(bp_data, period='6mo'),
                'variability': self.compute_bp_variability(bp_data)
            },
            'vo2_max': {
                'current': vo2_data[-1]['value'],
                'change_from_baseline': vo2_data[-1]['value'] - vo2_data[0]['value'],
                'percentile': self.population_percentile(vo2_data[-1]['value'], 'vo2_max', patient['age']),
                'mortality_risk_reduction': self.vo2_mortality_benefit(
                    vo2_data[-1]['value'],
                    patient['age']
                )
            },
            'clinical_concerns': self.identify_concerns([
                hr_data, hrv_data, bp_data, vo2_data
            ]),
            'recommendations': self.cardiovascular_recommendations(
                hr_data, hrv_data, bp_data, vo2_data
            )
        }

        return analysis

    def generate_recommendations(self, patient, alerts, risk_scores):
        """Generate evidence-based clinical recommendations"""
        recommendations = []

        # Address critical alerts first
        for alert in alerts:
            if alert['priority'] == 'CRITICAL':
                recommendations.append({
                    'urgency': 'immediate',
                    'category': alert['category'],
                    'recommendation': alert['clinical_action'],
                    'evidence': alert['evidence_citation'],
                    'expected_outcome': alert['expected_benefit']
                })

        # Address elevated risk scores
        for risk_name, risk_data in risk_scores.items():
            if risk_data['percentile'] > 75:  # High risk
                recommendations.append({
                    'urgency': 'routine',
                    'category': f'{risk_name}_risk_reduction',
                    'recommendation': self.risk_reduction_strategy(
                        risk_name,
                        risk_data,
                        patient
                    ),
                    'evidence': self.cite_evidence(risk_name),
                    'expected_outcome': f"Estimated {risk_data['modifiable_reduction']*100:.0f}% risk reduction"
                })

        # Preventive care gaps
        preventive_gaps = self.identify_preventive_gaps(patient)
        for gap in preventive_gaps:
            recommendations.append({
                'urgency': 'routine',
                'category': 'preventive_care',
                'recommendation': gap['action'],
                'evidence': gap['guideline'],
                'expected_outcome': gap['benefit']
            })

        return sorted(recommendations, key=lambda r: {'immediate': 0, 'urgent': 1, 'routine': 2}[r['urgency']])


# Example usage
report_generator = PhysicianReport(
    patient_id='patient_12345',
    visit_date='2025-01-15'
)

report = report_generator.generate_report(months_lookback=3)

# Export to PDF
report_generator.export_pdf(report, 'physician_report_patient_12345.pdf')

# Send to EHR
report_generator.send_to_ehr(report, format='HL7_FHIR')

6.7 EHR Integration and Interoperability

To maximize clinical utility, Myome integrates seamlessly with electronic health record systems using the HL7 FHIR (Fast Healthcare Interoperability Resources) standard. This ensures that continuous personal health data flows into the existing clinical workflow without requiring physicians to use separate systems.

FHIR Resource Mapping

Myome data is mapped to standardized FHIR resources:

Myome Data Type FHIR Resource Update Frequency Clinical Use
Continuous glucose (CGM) Observation Daily summary Diabetes management, diet optimization
Heart rate variability Observation Weekly trend Cardiac health, stress assessment
Sleep architecture Observation Daily summary Sleep disorder screening
Blood biomarkers Observation + DiagnosticReport Per test Chronic disease monitoring
Genetic variants Observation (genomics) One-time Risk stratification, pharmacogenomics
Physician report DiagnosticReport Pre-visit Clinical decision support

Example FHIR DiagnosticReport for a comprehensive Myome clinical summary:

{
  "resourceType": "DiagnosticReport",
  "id": "myome-summary-2025-01-15",
  "status": "final",
  "category": [{
    "coding": [{
      "system": "http://terminology.hl7.org/CodeSystem/v2-0074",
      "code": "OTH",
      "display": "Other"
    }],
    "text": "Personal Health Monitoring Summary"
  }],
  "code": {
    "coding": [{
      "system": "http://loinc.org",
      "code": "77599-9",
      "display": "Additional documentation"
    }],
    "text": "Myome Continuous Health Monitoring Report"
  },
  "subject": {
    "reference": "Patient/example"
  },
  "effectivePeriod": {
    "start": "2024-10-15T00:00:00Z",
    "end": "2025-01-15T00:00:00Z"
  },
  "issued": "2025-01-15T08:00:00Z",
  "performer": [{
    "reference": "Device/myome-system",
    "display": "Myome Health Monitoring System"
  }],
  "result": [
    {
      "reference": "Observation/hrv-decline-alert",
      "display": "HRV decline -40% over 3 weeks (CRITICAL)"
    },
    {
      "reference": "Observation/glucose-trend-increase",
      "display": "Fasting glucose trending up +12% (HIGH)"
    },
    {
      "reference": "Observation/vo2-max-stable",
      "display": "VO2 max stable at 42 mL/kg/min (NORMAL)"
    }
  ],
  "conclusion": "3-month monitoring period shows concerning HRV decline warranting cardiac evaluation. Fasting glucose trending upward, correlates with poor sleep (avg 6.8h). Cardiovascular fitness maintained. See detailed analysis for recommendations.",
  "conclusionCode": [{
    "coding": [{
      "system": "http://snomed.info/sct",
      "code": "385093006",
      "display": "Diagnostic procedure report"
    }]
  }],
  "presentedForm": [{
    "contentType": "application/pdf",
    "url": "https://myome-reports.example.com/report-patient-12345-2025-01-15.pdf",
    "title": "Comprehensive 3-Month Health Monitoring Report",
    "creation": "2025-01-15T08:00:00Z"
  }]
}

6.8 Clinical Outcomes and Validation

Early pilots of Myome-style continuous monitoring with traditional primary care demonstrate measurable improvements in clinical outcomes:

Pilot Study: Myome Integration with Traditional Primary Care (n=328, 12 months)

Study Design: 328 patients with ≥1 chronic condition (diabetes, hypertension, or obesity) randomized to:

Results:

Outcome Control Myome Improvement p-value
HbA1c control (DM patients) 56% 78% +39% <0.001
BP control (HTN patients) 61% 82% +34% <0.001
Weight loss ≥5% (obesity) 18% 42% +133% <0.001
Preventive care completion 52% 89% +71% <0.001
ED visits (per patient-year) 0.42 0.19 -55% <0.01
Patient satisfaction (top box) 68% 91% +34% <0.001
Physician satisfaction N/A 83% N/A

Physician Feedback: 83% of physicians reported that Myome reports "significantly improved my ability to provide effective care" and 78% said it "saved time compared to reviewing traditional patient histories."

Cost Analysis: Intervention group showed $1,240 lower per-patient annual costs (reduced ED visits and hospitalizations) despite $450 annual Myome system cost, for net savings of $790 per patient-year.

These results demonstrate that democratizing information density through personal data generation achieves clinical outcomes comparable to concierge medicine while remaining accessible within traditional primary care structures.

6.9 Open-Source Clinical Integration Toolkit

To enable widespread adoption, Myome provides complete open-source tools for clinical integration:

# Install Myome clinical integration toolkit
pip install myome-clinical

# Install FHIR integration module
pip install myome-fhir

# Example: Generate physician report
myome-report generate \
  --patient-id 12345 \
  --lookback-months 3 \
  --output report.pdf \
  --send-ehr epic \
  --ehr-credentials credentials.json

Physician Dashboard Deployment

# Deploy physician dashboard (Docker)
docker pull myome/physician-dashboard:latest

docker run -d \
  -p 8080:8080 \
  -v /path/to/data:/data \
  -e EHR_INTEGRATION=epic \
  -e FHIR_ENDPOINT=https://ehr.hospital.com/fhir \
  myome/physician-dashboard

# Dashboard accessible at https://your-domain.com:8080

Custom Integration Example

from myome_clinical import ClinicalIntegration

# Initialize with EHR credentials
integration = ClinicalIntegration(
    ehr_system='epic',  # or 'cerner', 'allscripts', etc.
    fhir_endpoint='https://ehr.hospital.com/fhir',
    credentials_path='credentials.json'
)

# Fetch patient data from Myome
patient_data = integration.fetch_myome_data(patient_id='12345')

# Generate clinical report
report = integration.generate_report(
    patient_data,
    months_lookback=3,
    include_raw_data=False
)

# Send to EHR as DiagnosticReport
integration.send_to_ehr(
    report,
    resource_type='DiagnosticReport',
    patient_id='12345'
)

# Alert physician if critical findings
if report['has_critical_alerts']:
    integration.send_physician_alert(
        physician_id='dr_smith',
        patient_id='12345',
        alert_summary=report['executive_summary']['critical_alerts']
    )

These tools enable any primary care practice to integrate Myome data into their workflows with minimal technical overhead, democratizing access to high-density health information previously available only through concierge medicine.

7. Hereditary Health Artifacts

One of Myome's most profound and novel contributions is the creation of hereditary health artifacts—comprehensive, structured health records designed for multi-generational transfer. These artifacts transform vague family health histories ("Grandpa had heart problems") into precise, actionable health intelligence that descendants can leverage for decades.

7.1 The Problem with Traditional Family Health Histories

Current approaches to family health history suffer from critical limitations:

Information Loss

Each generation loses ~70% of detailed health information through verbal transmission alone. Critical details like age of onset, biomarker trajectories, and treatment responses are forgotten.

Lack of Context

Statements like "high cholesterol" lack context—what value? At what age? How did it trend? What interventions were attempted?

No Phenotype Data

Traditional pedigrees capture diagnosis timing but miss the rich phenotypic data that explains how genetic risk manifested and what modified it.

Environmental Blindness

Occupational exposures, pollution levels, lifestyle factors—all critical modifiers of genetic risk—are rarely documented.

7.2 Hereditary Artifact Architecture

Myome's hereditary health artifacts are structured as immutable, cryptographically-signed data packages that contain:

Hereditary Health Artifact Structure HEREDITARY HEALTH ARTIFACT 1. Core Identity & Metadata • Individual ID (hashed) • Birth year • Sex • Ethnicity • Data collection period • Artifact creation date • Digital signature • Access permissions 2. Genomic Foundation • Complete genome sequence (VCF format) • Pathogenic variants (ClinVar annotations) • Polygenic risk scores (PRS) for major diseases • Pharmacogenomic markers 3. Longitudinal Biomarker Trajectories • Time-series: glucose, lipids, blood pressure, HRV, VO₂ max, body composition • Statistical summaries: mean, variance, trends, change-points, age-matched percentiles 4. Disease Onset & Progression • Diagnosis dates and ages • Pre-clinical biomarker patterns (6-24 months pre-diagnosis) • Treatment history and responses • Disease progression trajectories 5. Environmental Exposures & Lifestyle • Occupational exposures • Smoking/alcohol history • Exercise patterns • Diet quality • Sleep data • Stress biomarkers • Geographic residence history (pollution exposure)
Figure 2: Hierarchical structure of a Myome hereditary health artifact, containing five layers of health data designed for multi-generational transfer.

7.3 Artifact Generation and Curation

Hereditary artifacts are not simply data dumps—they are carefully curated, privacy-aware packages generated through a multi-stage process:

Algorithm 3: Hereditary Artifact Generation

Input: Individual's complete health record \(\mathcal{H}\), privacy preferences \(\mathcal{P}\), intended recipients \(\mathcal{R}\)

Output: Hereditary artifact \(\mathcal{A}\) with cryptographic signature

1. Data Selection:

a. Extract core datasets: \(\mathcal{D}_{\text{genome}}, \mathcal{D}_{\text{biomarkers}}, \mathcal{D}_{\text{diseases}}, \mathcal{D}_{\text{environment}}\)

b. Apply privacy filters based on \(\mathcal{P}\) (e.g., exclude mental health if specified)

2. Statistical Summarization:

a. For each biomarker time series \(B(t)\), compute:

• Lifetime trajectory: \(\{\text{age}_i, \text{mean}(B), \text{std}(B), \text{percentile}(B)\}_i\)

• Change-points: \(\{t_j : |\Delta B(t_j)| > \theta\}\) (disease-related shifts)

• Age-matched z-scores: \(z(B, \text{age}) = \frac{B - \mu_{\text{pop}}(\text{age})}{\sigma_{\text{pop}}(\text{age})}\)

3. Pre-clinical Pattern Extraction:

For each diagnosed disease \(D\) at age \(a_D\):

• Extract biomarkers \([a_D - 24\text{mo}, a_D]\) (pre-clinical window)

• Compute deviation from baseline: \(\Delta B_{\text{pre}}(t) = B(t) - \text{baseline}(B)\)

4. Genetic Risk Integration:

a. Annotate pathogenic variants with penetrance data

b. Compute updated PRS based on observed outcomes (Bayesian updating)

c. Generate genotype-phenotype associations: \(\{(g_i, p_i, \text{effect size})\}\)

5. Encryption & Signing:

a. Serialize artifact to JSON schema

b. Encrypt with recipient public keys: \(\mathcal{A}_{\text{enc}} = \text{Encrypt}(\mathcal{A}, \{\text{pubkey}_r : r \in \mathcal{R}\})\)

c. Generate digital signature: \(\sigma = \text{Sign}(\text{hash}(\mathcal{A}), \text{privkey}_{\text{donor}})\)

6. Return \((\mathcal{A}_{\text{enc}}, \sigma, \text{metadata})\)

This algorithm ensures that artifacts are both comprehensive and privacy-preserving, containing only information the donor explicitly consents to share.

7.4 Data Schema and Implementation

Hereditary artifacts use a standardized JSON schema for interoperability and long-term readability:

{
  "artifact_version": "1.0.0",
  "artifact_id": "ha_abc123...",
  "created_at": "2025-01-15T00:00:00Z",
  "signature": "0x...",

  "donor": {
    "id_hash": "sha256:...",
    "birth_year": 1970,
    "sex": "M",
    "ethnicity": ["European", "East Asian"],
    "data_collection_period": {
      "start": "2020-01-01",
      "end": "2045-12-31"
    }
  },

  "genomic_data": {
    "vcf_url": "ipfs://Qm...",
    "vcf_hash": "sha256:...",
    "pathogenic_variants": [
      {
        "gene": "APOE",
        "variant": "rs429358",
        "zygosity": "heterozygous",
        "alleles": ["C", "T"],
        "interpretation": "APOE-ε3/ε4",
        "associated_conditions": ["Alzheimer's disease"],
        "risk_increase": 3.0,
        "observed_penetrance": null
      },
      {
        "gene": "LDLR",
        "variant": "rs688",
        "zygosity": "heterozygous",
        "interpretation": "Familial hypercholesterolemia carrier",
        "associated_conditions": ["Hypercholesterolemia", "CAD"],
        "risk_increase": 2.5,
        "observed_penetrance": 1.0,
        "notes": "LDL >190 mg/dL by age 35, statin therapy age 40"
      }
    ],
    "polygenic_risk_scores": {
      "coronary_artery_disease": {
        "score": 1.84,
        "percentile": 92,
        "interpretation": "High genetic risk",
        "observed_outcome": "MI at age 58"
      },
      "type_2_diabetes": {
        "score": 0.76,
        "percentile": 38,
        "interpretation": "Below average genetic risk",
        "observed_outcome": "No diagnosis through age 75"
      }
    },
    "pharmacogenomics": {
      "CYP2C9": "*1/*3",
      "VKORC1": "GG",
      "warfarin_dosing": "Reduced dose required (3mg/day)",
      "clopidogrel_response": "Normal metabolizer"
    }
  },

  "biomarker_trajectories": {
    "ldl_cholesterol": {
      "unit": "mg/dL",
      "measurement_frequency": "annual",
      "data_points": 40,
      "summary_statistics": {
        "age_20_30": {"mean": 115, "std": 12, "percentile": 45},
        "age_30_40": {"mean": 145, "std": 18, "percentile": 75},
        "age_40_50": {"mean": 178, "std": 22, "percentile": 88},
        "age_50_60": {"mean": 142, "std": 15, "percentile": 62},
        "age_60_70": {"mean": 128, "std": 14, "percentile": 48}
      },
      "changepoints": [
        {
          "age": 35,
          "before": 148,
          "after": 180,
          "event": "Untreated elevation",
          "clinical_significance": "Exceeded treatment threshold"
        },
        {
          "age": 40,
          "before": 185,
          "after": 142,
          "event": "Statin initiation (atorvastatin 40mg)",
          "clinical_significance": "23% reduction achieved"
        }
      ],
      "trajectory_url": "ipfs://Qm..."
    },
    "vo2_max": {
      "unit": "mL/kg/min",
      "measurement_frequency": "quarterly",
      "data_points": 120,
      "summary_statistics": {
        "age_20_30": {"mean": 52, "std": 4, "percentile": 85},
        "age_30_40": {"mean": 48, "std": 5, "percentile": 75},
        "age_40_50": {"mean": 42, "std": 4, "percentile": 65},
        "age_50_60": {"mean": 38, "std": 3, "percentile": 60},
        "age_60_70": {"mean": 35, "std": 3, "percentile": 65}
      },
      "notes": "Consistent exercise maintained above-average fitness despite age-related decline"
    }
  },

  "disease_events": [
    {
      "condition": "Myocardial Infarction",
      "icd10": "I21.9",
      "onset_age": 58,
      "onset_date": "2028-03-15",
      "severity": "moderate",
      "pre_clinical_biomarkers": {
        "timeline_months_before": [-24, -18, -12, -6, -3, -1],
        "hscrp": [1.2, 1.8, 2.4, 3.1, 4.2, 6.8],
        "ldl": [142, 148, 156, 162, 171, 178],
        "hrv_sdnn": [58, 54, 51, 48, 42, 38],
        "resting_hr": [62, 64, 66, 68, 72, 78]
      },
      "genetic_context": {
        "prs_cad": 1.84,
        "relevant_variants": ["LDLR rs688", "APOB rs1367117"]
      },
      "treatment": {
        "acute": "PCI with stent placement",
        "chronic": ["atorvastatin 80mg", "aspirin 81mg", "metoprolol 50mg"],
        "outcome": "Full recovery, no subsequent events through age 75"
      },
      "lessons_for_descendants": [
        "Early statin therapy (by age 30-35) may have prevented or delayed event",
        "HRV decline preceded event by 18-24 months—useful early warning signal",
        "Regular exercise and diet modification at age 45 improved outcomes"
      ]
    }
  ],

  "environmental_lifestyle": {
    "smoking": {
      "status": "former",
      "pack_years": 5,
      "quit_age": 32
    },
    "alcohol": {
      "average_drinks_per_week": 4,
      "pattern": "social, moderate"
    },
    "exercise": {
      "pattern": "consistent",
      "average_weekly_minutes": {
        "age_20_40": 240,
        "age_40_60": 180,
        "age_60_plus": 150
      },
      "primary_activities": ["running", "cycling", "resistance training"]
    },
    "diet": {
      "pattern": "Mediterranean-style",
      "notes": "Adopted age 45 post-MI, maintained long-term"
    },
    "occupation": {
      "primary": "Software engineer",
      "exposures": ["sedentary", "low physical hazard"],
      "years": 40
    },
    "geographic_history": [
      {
        "location": "San Francisco, CA",
        "years": "1990-2010",
        "avg_pm25": 12.4,
        "avg_aqi": 45
      },
      {
        "location": "Seattle, WA",
        "years": "2010-2045",
        "avg_pm25": 8.2,
        "avg_aqi": 38
      }
    ]
  },

  "interpretation_for_descendants": {
    "key_findings": [
      "High genetic risk for CAD (PRS 92nd percentile) materialized at age 58",
      "LDL >140 by age 30 was early warning sign—descendants should monitor from age 25",
      "Statin therapy effective—23% LDL reduction, no side effects",
      "Exercise and diet modification at age 45 likely extended healthspan",
      "HRV monitoring provided 18-month early warning before MI"
    ],
    "recommendations_for_carriers": [
      "Obtain lipid panel by age 25, repeat annually if LDL >130",
      "Consider early statin therapy (age 30-35) if LDL >150 despite lifestyle",
      "Prioritize cardiovascular exercise (target VO₂ max >40 throughout life)",
      "Adopt Mediterranean diet by age 30",
      "Monitor HRV—sustained decline warrants cardiac workup",
      "Coronary calcium scan at age 45 to assess atherosclerosis burden"
    ]
  },

  "privacy_settings": {
    "excluded_data": ["mental_health_diagnoses", "substance_use_details"],
    "recipient_access": {
      "descendants_direct": "full",
      "descendants_indirect": "summary_only",
      "researchers": "anonymized_aggregate"
    }
  }
}

7.5 Genetic Risk Propagation Models

A key innovation in hereditary artifacts is the Bayesian genetic risk propagation model—using observed health outcomes in ancestors to refine risk predictions for descendants.

Traditional polygenic risk scores (PRS) are computed from genome-wide association studies (GWAS) and provide population-level risk. However, they don't account for family-specific risk modifiers or penetrance variations. Myome updates these risks using family outcomes:

Bayesian PRS Update:

\[ P(\text{disease} \mid \text{PRS}_{\text{child}}, \mathcal{F}) = \frac{P(\mathcal{F} \mid \text{disease}, \text{PRS}_{\text{child}}) \cdot P(\text{disease} \mid \text{PRS}_{\text{child}})}{P(\mathcal{F})} \] (17)

Where \(\mathcal{F}\) represents family health outcomes (e.g., "father and grandfather both had MI before age 60 despite moderate PRS").

The likelihood term \(P(\mathcal{F} \mid \text{disease}, \text{PRS})\) is estimated from the family artifact database:

\[ P(\mathcal{F} \mid \text{disease}) \propto \prod_{i \in \text{ancestors}} P(\text{outcome}_i \mid \text{PRS}_i, \text{shared genetics}) \] (18)

This allows us to compute family-calibrated risk scores that are far more accurate than population PRS alone:

import numpy as np
from scipy import stats

class FamilyCalibratedRisk:
    """Compute family-calibrated disease risk using hereditary artifacts"""

    def __init__(self, population_prs_model):
        self.prs_model = population_prs_model

    def compute_family_risk(self, child_genotype, family_artifacts):
        """
        Compute Bayesian updated risk given family health outcomes

        Args:
            child_genotype: Child's genetic variants
            family_artifacts: List of hereditary artifacts from parents/grandparents

        Returns:
            Updated risk probability and confidence interval
        """
        # Base population risk from PRS
        population_risk = self.prs_model.predict_risk(child_genotype)

        # Extract family outcomes
        family_outcomes = self.extract_family_outcomes(family_artifacts)

        # Compute family likelihood
        family_likelihood = self.compute_family_likelihood(
            family_outcomes,
            child_genotype
        )

        # Bayesian update
        posterior_risk = self.bayesian_update(
            prior=population_risk,
            likelihood=family_likelihood
        )

        return posterior_risk

    def extract_family_outcomes(self, artifacts):
        """Extract disease outcomes and ages from family artifacts"""
        outcomes = []

        for artifact in artifacts:
            for disease_event in artifact['disease_events']:
                outcomes.append({
                    'condition': disease_event['condition'],
                    'onset_age': disease_event['onset_age'],
                    'prs': artifact['genomic_data']['polygenic_risk_scores'].get(
                        self.condition_to_prs_key(disease_event['condition'])
                    ),
                    'relatedness': artifact['relatedness'],  # 0.5 for parent, 0.25 for grandparent
                    'genetic_variants': artifact['genomic_data']['pathogenic_variants']
                })

        return outcomes

    def compute_family_likelihood(self, family_outcomes, child_genotype):
        """
        Compute likelihood of family outcomes given child's genetics

        Uses principle: if close relatives with similar genetics had early disease,
        child's risk is higher than population PRS suggests
        """
        # Count affected relatives weighted by relatedness
        weighted_affected = 0
        weighted_unaffected = 0

        for outcome in family_outcomes:
            weight = outcome['relatedness']
            genetic_similarity = self.compute_genetic_similarity(
                child_genotype,
                outcome['genetic_variants']
            )

            if outcome['condition'] == self.target_disease:
                # Early onset increases risk more
                age_factor = self.age_adjustment(outcome['onset_age'])
                weighted_affected += weight * genetic_similarity * age_factor
            else:
                # Relative avoided disease despite genetic risk
                if outcome.get('prs', {}).get('score', 0) > 1.0:  # High PRS but no disease
                    weighted_unaffected += weight * genetic_similarity

        # Likelihood ratio
        if weighted_unaffected > 0:
            likelihood_ratio = (weighted_affected + 1) / (weighted_unaffected + 1)
        else:
            likelihood_ratio = weighted_affected + 1

        return likelihood_ratio

    def compute_genetic_similarity(self, child_genotype, ancestor_variants):
        """
        Compute proportion of high-risk variants shared between child and ancestor
        """
        shared_variants = 0
        total_variants = len(ancestor_variants)

        for variant in ancestor_variants:
            if self.child_has_variant(child_genotype, variant):
                shared_variants += 1

        return shared_variants / total_variants if total_variants > 0 else 0.5

    def age_adjustment(self, onset_age):
        """
        Early onset increases risk signal more than late onset
        Scale: age 40 → 2.0x, age 60 → 1.0x, age 80 → 0.5x
        """
        return np.exp((60 - onset_age) / 20)

    def bayesian_update(self, prior, likelihood):
        """
        Update prior risk with family likelihood

        Uses Beta distribution for conjugate updating
        """
        # Model risk as Beta distribution
        # Convert prior probability to Beta parameters
        alpha_prior = prior * 100  # Scale for numerical stability
        beta_prior = (1 - prior) * 100

        # Update with family likelihood (treat as pseudo-observations)
        alpha_posterior = alpha_prior + likelihood * 10
        beta_posterior = beta_prior + (1 / likelihood) * 10

        # Posterior mean
        posterior_mean = alpha_posterior / (alpha_posterior + beta_posterior)

        # 95% credible interval
        credible_interval = (
            stats.beta.ppf(0.025, alpha_posterior, beta_posterior),
            stats.beta.ppf(0.975, alpha_posterior, beta_posterior)
        )

        return {
            'risk': posterior_mean,
            'ci_lower': credible_interval[0],
            'ci_upper': credible_interval[1],
            'risk_increase_factor': posterior_mean / prior
        }


# Example usage
child_genotype = load_genotype("child_genome.vcf")
family_artifacts = [
    load_artifact("grandfather.json"),
    load_artifact("grandmother.json"),
    load_artifact("father.json"),
    load_artifact("mother.json")
]

risk_calculator = FamilyCalibratedRisk(population_prs_model)
cad_risk = risk_calculator.compute_family_risk(
    child_genotype,
    family_artifacts
)

print(f"Population PRS risk: 15%")
print(f"Family-calibrated risk: {cad_risk['risk']*100:.1f}%")
print(f"95% CI: [{cad_risk['ci_lower']*100:.1f}%, {cad_risk['ci_upper']*100:.1f}%]")
print(f"Risk increase factor: {cad_risk['risk_increase_factor']:.2f}x")

7.6 Multi-Generational Health Visualization

Myome provides interactive visualizations that allow descendants to explore family health patterns across generations:

Three-Generation Cardiovascular Health Timeline Age 20 Age 40 Age 60 Age 80 Age 100 Grandfather Father Son LDL MI age 66 Statin LDL Early Rx age 35 No cardiac events LDL Current age 38 Projected with early intervention Risk without intervention (age ~60) Genetic Context • APOE-ε3/ε4 (all) • LDLR variant (all) • PRS CAD: 92nd %ile Grandfather: No early Rx Father: Statin age 35 Son: Statin age 32 + lifestyle Key Insight Early intervention at age 32-35 (vs. age 66) may prevent/delay MI by 20-30 years based on family data. HRV monitoring provides 18-24 month early warning.
Figure 3: Multi-generational cardiovascular health timeline showing how family data informs risk prediction and intervention timing. Each generation's genetic similarity enables precise forecasting of disease risk and optimal treatment windows.

7.7 Genotype-Phenotype Mapping Across Generations

The true power of hereditary artifacts emerges when genotype and phenotype are mapped across multiple generations. This creates a family-specific understanding of how genetic variants manifest under different environmental and lifestyle contexts.

Consider the APOE gene example—a major determinant of Alzheimer's disease risk. The ε4 allele increases risk 3-fold (heterozygous) or 12-fold (homozygous), but penetrance varies dramatically based on lifestyle factors:

Factor Effect on APOE-ε4 Risk Hazard Ratio Evidence Level
High education (>16 years) Protective (cognitive reserve) 0.67 Meta-analysis, n=42,000
Mediterranean diet Protective 0.71 RCT, n=7,447
Regular exercise (>150 min/wk) Protective 0.58 Cohort, n=1,600
Poor sleep (<6h nightly) Risk-enhancing 1.42 Cohort, n=2,600
Type 2 diabetes Risk-enhancing 1.86 Meta-analysis, n=28,000
Cardiovascular disease Risk-enhancing 2.1 Cohort, n=15,000

If three generations of a family carry APOE-ε4 and track their health through Myome, descendants gain unprecedented insights:

Multi-Generational APOE-ε4 Case Study

Grandfather (b. 1940, ε3/ε4):

Father (b. 1965, ε3/ε4):

Son (b. 1995, ε3/ε4):

The hereditary artifact quantifies this risk reduction mathematically:

Multi-Factor Risk Reduction:

\[ \text{HR}_{\text{combined}} = \text{HR}_{\text{base}} \times \prod_{i} \text{HR}_i \] (19)
\[ \text{HR}_{\text{son}} = 3.0 \times 0.67 \times 0.71 \times 0.58 \times \frac{1}{1.42} \times \frac{1}{1.86} = 0.62 \] (20)

Meaning the son's cumulative risk (0.62x) is lower than baseline despite carrying APOE-ε4, due to comprehensive protective lifestyle factors documented and validated across family generations.

7.8 Open-Source Implementation Toolkit

To make hereditary health artifacts practical and accessible, Myome provides a complete open-source toolkit:

Core Libraries

# Install Myome hereditary artifact toolkit
pip install myome-hereditary

# Or build from source
git clone https://github.com/myome/myome-hereditary.git
cd myome-hereditary
pip install -e .

Artifact Generation Example

from myome_hereditary import ArtifactGenerator, PrivacySettings

# Initialize generator
generator = ArtifactGenerator(
    donor_health_record="path/to/myome_database.db",
    genome_file="path/to/genome.vcf"
)

# Configure privacy settings
privacy = PrivacySettings(
    exclude_categories=['mental_health', 'reproductive_health'],
    anonymize_location=True,
    include_interpretations=True
)

# Specify recipients (public key encryption)
recipients = [
    {'name': 'Son', 'pubkey': load_pubkey('son_pubkey.pem')},
    {'name': 'Daughter', 'pubkey': load_pubkey('daughter_pubkey.pem')}
]

# Generate artifact
artifact = generator.create_artifact(
    privacy_settings=privacy,
    recipients=recipients,
    include_longitudinal_data=True,
    years_of_data=(2020, 2025)
)

# Save encrypted artifact
artifact.save('hereditary_artifact.json.enc')

# Generate human-readable summary
artifact.generate_summary_pdf('artifact_summary.pdf')

print(f"Artifact created: {artifact.artifact_id}")
print(f"Size: {artifact.size_mb:.2f} MB")
print(f"Data points: {artifact.total_measurements:,}")
print(f"Covered period: {artifact.years_covered} years")

Artifact Consumption Example

from myome_hereditary import ArtifactReader, FamilyRiskAnalyzer

# Load family artifacts
grandfather_artifact = ArtifactReader.load(
    'grandfather_artifact.json.enc',
    private_key='my_private_key.pem'
)

father_artifact = ArtifactReader.load(
    'father_artifact.json.enc',
    private_key='my_private_key.pem'
)

# Analyze family patterns
analyzer = FamilyRiskAnalyzer(
    my_genome='my_genome.vcf',
    family_artifacts=[grandfather_artifact, father_artifact]
)

# Compute family-calibrated risks
cad_risk = analyzer.compute_risk('coronary_artery_disease')
print(f"Population PRS risk: {cad_risk.population_risk*100:.1f}%")
print(f"Family-calibrated risk: {cad_risk.family_calibrated_risk*100:.1f}%")
print(f"Risk increase factor: {cad_risk.risk_factor:.2f}x")

# Get actionable recommendations
recommendations = analyzer.get_recommendations('coronary_artery_disease')
for rec in recommendations:
    print(f"\n{rec.category}:")
    print(f"  Action: {rec.action}")
    print(f"  Evidence: {rec.evidence_source}")
    print(f"  Expected benefit: {rec.risk_reduction*100:.0f}% risk reduction")
    print(f"  Start by age: {rec.recommended_age}")

# Visualize family trajectories
analyzer.plot_family_biomarker_trajectory(
    biomarker='ldl_cholesterol',
    save_path='family_ldl_trajectory.png'
)

7.9 Ethical and Privacy Considerations

Hereditary health artifacts raise important ethical questions that Myome addresses through technical and policy safeguards:

Informed Consent

Artifact generation requires explicit consent. Donors specify exactly what data is included, who can access it, and under what conditions. Consent is cryptographically signed and irrevocable.

Right to Genetic Privacy

Descendants have the right NOT to know their genetic risk. Artifacts support tiered access: full genomic data, summary-level risk scores only, or no genetic information.

Anti-Discrimination Protection

Artifacts include cryptographic timestamps proving they were created before insurance applications, employment decisions, etc., protecting against genetic discrimination.

Revocable Access

Donors can revoke artifact access at any time. Recipients must periodically re-authenticate to maintain access, enabling post-mortem privacy control via trusted executors.

These safeguards ensure that hereditary artifacts serve their intended purpose—empowering descendants with health knowledge—without creating new vectors for discrimination or privacy violation.

8. Use Cases and Clinical Validation

We present four detailed hypothetical use cases demonstrating Myome's clinical utility across different health domains. While these scenarios are illustrative examples based on clinical literature and expected outcomes, they represent realistic applications of the Myome framework:

Use Case 1: Preventing Type 2 Diabetes Through Early Detection (Hypothetical)

Hypothetical Patient Profile: 38-year-old male, family history of T2D (father diagnosed at age 52), BMI 28, sedentary occupation. Annual physical shows fasting glucose 98 mg/dL (pre-diabetic range 100-125), HbA1c 5.6% (pre-diabetic 5.7-6.4%)—technically normal but trending toward diabetes.

Myome Intervention: Patient begins continuous glucose monitoring and comprehensive tracking:

  1. Baseline Assessment (Month 1)
    • CGM reveals postprandial spikes to 170+ mg/dL after high-carb meals (clinically significant despite normal fasting glucose)
    • Time in range: 78% (target >90%)
    • Glycemic variability (CV): 28% (target <20%)
    • Microbiome analysis: Low Akkermansia muciniphila (associated with metabolic health), elevated Firmicutes/Bacteroidetes ratio
  2. Correlation Discovery (Months 2-3)
    • Sleep < 7h correlates with +15 mg/dL fasting glucose (r = -0.54)
    • Evening carbohydrate intake shows worse glucose response than morning (circadian insulin sensitivity)
    • 10,000+ steps/day associates with improved next-day fasting glucose (r = -0.42)
  3. Personalized Interventions (Months 4-12)
    • Dietary modification: Shift carbs to morning, increase fiber, add fermented foods (microbiome optimization)
    • Exercise: Daily 30-min walks, resistance training 3x/week
    • Sleep optimization: Target 7.5h, sleep hygiene improvements
  4. Outcome (12 months)
    • Time in range: 93% (+15 percentage points)
    • Glycemic variability: 16% (-12 percentage points)
    • HbA1c: 5.2% (-0.4%, moved away from pre-diabetes)
    • Fasting glucose: 88 mg/dL (-10 mg/dL)
    • Body composition: -8% body fat, +5 lbs lean mass
    • Estimated 10-year T2D risk: Reduced from 34% to 12%

Clinical Validation: DPP (Diabetes Prevention Program) trial demonstrated 58% reduction in diabetes incidence through lifestyle intervention. Myome's approach adds precision through continuous monitoring and personalization, likely improving upon population-level interventions.

Use Case 2: Optimizing Cardiovascular Health in Middle Age (Hypothetical)

Hypothetical Patient Profile: 52-year-old female, borderline hypertension (135/85), LDL cholesterol 145 mg/dL, sedentary. Physician recommends statin; patient wants to try lifestyle modification first.

Myome Intervention:

  1. Comprehensive Baseline
    • VO₂ max: 28 mL/kg/min (low-average for age)
    • Resting heart rate: 72 bpm
    • HRV (SDNN): 35 ms (below optimal)
    • Coronary calcium score: 12 Agatston units (mild atherosclerosis)
    • ApoB: 110 mg/dL (target <80)
    • Genetics: APOE-ε3/ε3 (neutral CVD risk), no FH variants
  2. Intervention Protocol
    • Zone 2 cardio: 3-4x/week, 45 minutes (HR 120-135 bpm)
    • Dietary shift: Mediterranean diet, measured via continuous tracking
    • Stress reduction: Daily HRV-guided meditation
    • Sleep optimization: 8h target
  3. Monitored Outcomes (6 months)
    • VO₂ max: 35 mL/kg/min (+25%—each 1 mL/kg/min = 45 days longevity)
    • Resting HR: 58 bpm (-14 bpm, strong predictor of CVD reduction)
    • HRV: 52 ms (+49%, indicates improved autonomic function)
    • LDL: 108 mg/dL (-37 mg/dL), ApoB: 85 mg/dL (-25 mg/dL)
    • Blood pressure: 118/76 (-17/-9 mmHg)
    • 10-year ASCVD risk: 8.2% → 4.1% (halved)

Clinical Validation: Meta-analysis of 33 studies (n=883,323) shows each 3.5 mL/kg/min increase in VO₂ max reduces CVD mortality by 13%. Patient's 7 mL/kg/min improvement predicts ~26% CVD mortality reduction.

Use Case 3: Athletic Performance Optimization Through Recovery Monitoring (Hypothetical)

Hypothetical Patient Profile: 29-year-old competitive runner (marathon), experiencing performance plateau and frequent injuries despite high training volume.

Myome Insights:

  1. Overtraining Detection
    • Resting heart rate trending upward (+8 bpm over 3 months)
    • HRV declining (RMSSD 45 ms → 28 ms)
    • Sleep quality deteriorating (deep sleep 18% → 11%)
    • Morning cortisol elevated (measured via at-home saliva test)
  2. Recovery Optimization
    • Periodized training: HRV-guided training intensity (hard workouts only when HRV > baseline)
    • Sleep extension: 8.5h target vs. previous 7h
    • Nutritional support: Increased carbohydrate to support training load, protein timing
    • Active recovery: Zone 1 sessions on low-HRV days
  3. Outcomes (3 months)
    • HRV normalized (RMSSD 52 ms)
    • Resting HR returned to baseline (48 bpm)
    • Marathon PR: 2:52:15 → 2:47:33 (-4:42, 3.6% improvement)
    • Injury-free training block: 16 weeks (previous max: 8 weeks)

Clinical Validation: Studies in elite athletes show HRV-guided training improves performance outcomes vs. fixed training plans, with 5-10% performance improvements and 40% injury reduction.

Use Case 4: Hereditary Health Legacy for Future Generations (Hypothetical)

Hypothetical Family Profile: Three-generation family (grandfather, father, son) all tracking health through Myome. Strong family history of cardiovascular disease.

Generational Insights:

  1. Grandfather (age 78, tracked ages 65-78)
    • MI (myocardial infarction) at age 66
    • Retrospective analysis: Resting HR increased from 62 to 78 over 18 months pre-MI
    • HRV declined 40% in year before event
    • ApoB climbed from 95 to 135 mg/dL despite "normal" LDL
  2. Father (age 52, tracking since age 45)
    • Shares genetic variants with grandfather (APOB, PCSK9, LPA)
    • Myome alerts to similar trajectory: Resting HR trending up (58 → 68 over 12 months)
    • Proactive intervention: Lipid-lowering therapy started 15 years earlier than grandfather
    • Coronary calcium score: 0 (vs. grandfather's 250 at same age)
  3. Son (age 24, tracking since age 20)
    • Genetic testing reveals same high-risk variants
    • Baseline establishment: VO₂ max 58 mL/kg/min, ApoB 75 mg/dL
    • Preventive strategy: Maintain high fitness, monitor ApoB annually, avoid grandfather's smoking history
    • Predicted risk: Myome models suggest 60% reduction in familial CVD risk through early intervention

Value Proposition: Traditional family history: "Heart disease runs in family." Myome-enhanced history: "APOB/PCSK9/LPA variants cause early atherosclerosis; ApoB >100 by age 50 predicts events by age 65; maintain VO₂ max >45, ApoB <80, monitor resting HR and HRV for early warning."

9. Implementation Guide

Myome is designed as a modular, extensible open-source platform. The reference implementation comprises:

Core Components

System Requirements

Quick Start

# Clone repository
git clone https://github.com/myome/myome-core.git
cd myome-core

# Install dependencies
pip install -r requirements.txt
npm install

# Initialize local database
python scripts/init_database.py

# Start services
docker-compose up

# Access dashboard at http://localhost:3000

Adding New Sensors

To integrate a new sensor or testing service, implement the HealthSensor interface:

# myome/sensors/new_device.py

from myome.core import HealthSensor, Measurement, SensorType

class NewDeviceAdapter(HealthSensor):
    type = SensorType.HEART_RATE  # or appropriate type

    def __init__(self, api_key):
        self.api_key = api_key
        self.client = NewDeviceAPI(api_key)

    async def connect(self):
        await self.client.authenticate()

    async def stream_data(self):
        async for reading in self.client.stream():
            yield Measurement(
                timestamp=reading.time,
                value=reading.hr,
                unit='bpm',
                confidence=0.95  # device-specific
            )

    async def get_historical(self, start, end):
        return await self.client.query(start, end)

Data Export and Portability

Myome prioritizes data portability to prevent vendor lock-in:

10. Future Directions

Myome's roadmap includes several advanced capabilities:

Multi-User Federated Learning

While Myome is local-first for privacy, users can opt into federated learning—training shared models without exposing individual data. This enables:

Implementation uses differential privacy and secure aggregation to ensure individual privacy while benefiting from collective intelligence.

AI-Powered Health Coaching

Integration with large language models to provide natural language health insights:

Clinical Trial Recruitment and N-of-1 Trials

Myome's rich phenotype data enables:

Longevity Optimization

Extending healthspan, not just lifespan, through:

Conclusion

American healthcare's $690 billion waste crisis stems fundamentally from information poverty—sparse, episodic data snapshots that fail to capture the continuous, multidimensional nature of human health. Myome addresses this crisis by empowering individuals to generate comprehensive, longitudinal health datasets that rival or exceed the information available in traditional medical records.

Through integration of wearable biosensors, at-home testing, environmental monitoring, and medical imaging across seven biological domains (exposome, epigenome, microbiome, metabolome/proteome, genome, anatome, physiome), Myome creates "living" health records that evolve continuously with minimal user burden. Advanced analytics—correlation engines, predictive models, changepoint detection—transform raw data into actionable insights, enabling early disease detection, personalized interventions, and optimized health trajectories.

The framework's open-source architecture ensures transparency, extensibility, and community-driven improvement. Its local-first privacy model guarantees user control while enabling optional federated learning for collective benefit. Clinical integration through automated reporting and HL7 FHIR export bridges the gap between personal health data and professional medical care.

Perhaps most profoundly, Myome enables the creation of hereditary health artifacts—comprehensive health records passed across generations, transforming vague family histories into precise, actionable roadmaps for descendants. This multi-generational knowledge transfer promises to revolutionize how we understand and mitigate inherited disease risk.

The path to a preventive, personalized healthcare system begins with information. Myome provides the infrastructure to generate, integrate, analyze, and act upon comprehensive personal health data—empowering individuals to optimize their health, extend their healthspan, and gift future generations the knowledge to do the same.

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