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Nuclear Aging Morphometry Dataset: TCGA Bladder Cancer Nuclei Features for Longevity Research Dataset Description This dataset provides nuclear morphometric features extracted from TCGA bladder cancer histopathology slides, specifically designed for aging and longevity research. The dataset contains quantitative shape measurements of >1M individual nuclei across multiple fields of view, enabling machine learning approaches to study cellular aging, senescence… See the full description on the dataset page: https://huggingface.co/datasets/longevity-db/pan-cancer-nuclei-seg.

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Nuclear Aging Morphometry Dataset: TCGA Bladder Cancer Nuclei Features for Longevity Research

Dataset Description

This dataset provides nuclear morphometric features extracted from TCGA bladder cancer histopathology slides, specifically designed for aging and longevity research. The dataset contains quantitative shape measurements of >1M individual nuclei across multiple fields of view, enabling machine learning approaches to study cellular aging, senescence biomarkers, and age-related nuclear morphology changes.

🔬 Why Nuclear Morphology Matters for Aging Research

Nuclear morphology serves as a quantifiable predictor of cellular senescence and aging:

  • —Nuclear enlargement and elongation are hallmarks of cellular senescence (Zhu et al., 2021)
  • —Aspect ratio increases correlate with cellular age and senescence induction
  • —Shape irregularity reflects aging-associated nuclear dysfunction
  • —Deep learning models can predict senescence from nuclear morphology with 95% accuracy

This dataset bridges the gap between large-scale cancer genomics data (TCGA) and quantitative aging biology, enabling novel aging clock development and senescence biomarker discovery.

Dataset Structure

📊 Main Dataset Files

  • —`nuclei_features.parquet`: Nuclear morphometric features (~1M+ nuclei)
  • —`clinical_metadata.parquet`: Patient clinical data with age information
  • —`tcga_cdr_supplement.parquet`: TCGA Clinical Data Resource supplement

🔢 Nuclear Features (per nucleus)

FeatureDescriptionAging Relevance
areaNuclear area in μm² (converted from pixels)↑ Increases with senescence
aspect_ratioLength/width ratio (≥1.0)↑ Nuclear elongation with aging
circularity4πA/P² (1.0 = perfect circle)↓ Decreases with age-related irregularity
convexityArea/convexhullarea↓ Shape complexity increases with aging
perimeterNuclear boundary length in μm↑ Irregular boundaries in aged cells
slide_idTCGA slide identifierLinks to patient metadata
nucleus_idUnique nucleus identifierFor tracking individual nuclei

🔧 Technical Metadata & Processing Parameters

Each nucleus record includes comprehensive technical metadata for reproducibility:

Segmentation Algorithm Parameters
ParameterDescriptionValue/Range
curvature_weightContour smoothness parameterAlgorithm-specific
min_sizeMinimum nucleus size filter (pixels)Removes artifacts
max_sizeMaximum nucleus size filter (pixels)Removes artifacts
ms_kernelMean shift clustering kernelEdge detection
declump_typeMethod for separating clustered nucleiAlgorithm choice
levelset_num_itersLevel set segmentation iterationsConvergence control
mppMicrons per pixel (crucial!)0.5 μm/px (20x mag)
Spatial & Image Context
ParameterDescriptionUsage
image_width, image_heightOriginal WSI dimensionsFull image context
tile_minx, tile_minyTile position in WSISpatial localization
tile_width, tile_heightTile dimensionsProcessing window
patch_minx, patch_minyPatch position in tileFine-scale location
patch_width, patch_heightAnalysis patch sizeAnalysis window
output_levelWSI pyramid level usedResolution level
Raw Measurements & Identifiers
ParameterDescriptionUnits
AreaInPixelsRaw pixel area measurementpixels²
PhysicalSizePhysical area measurementμm²
PolygonNucleus boundary coordinatespixel coordinates
subject_idPatient identifierTCGA format
case_idCase identifierLinks to clinical data
analysis_idProcessing pipeline IDReproducibility
analysis_descPipeline descriptionMethods documentation

👥 Clinical Metadata Features

FeatureDescriptionAging Application
age_at_diagnosisPatient age (years)Primary aging variable
genderPatient genderAge-gender interaction analysis
stageCancer stageDisease-aging interactions
gradeTumor gradeSenescence-cancer progression
tcga_barcodeTCGA patient IDLinks to genomic data

🧬 Aging Research Applications

1. Nuclear Aging Clocks

Build machine learning models to predict patient age from nuclear morphology:

python
import pandas as pd
from sklearn.ensemble import RandomForestRegressor

# Load data
nuclei_df = pd.read_parquet('nuclei_features.parquet')
clinical_df = pd.read_parquet('clinical_metadata.parquet')

# Merge with age data
data = nuclei_df.merge(clinical_df, on='tcga_barcode')

# Train age prediction model
features = ['area', 'aspect_ratio', 'circularity', 'convexity']
X = data[features]
y = data['age_at_diagnosis']

model = RandomForestRegressor(n_estimators=100)
model.fit(X, y)

# Feature importance for aging
aging_features = pd.DataFrame({
    'feature': features,
    'importance': model.feature_importances_
}).sort_values('importance', ascending=False)

2. Senescence Biomarker Discovery

Identify morphometric signatures of cellular senescence:

python
# Compare nuclear features across age groups
young = data[data['age_at_diagnosis'] < 50]
old = data[data['age_at_diagnosis'] > 70]

senescence_markers = {}
for feature in features:
    young_mean = young[feature].mean()
    old_mean = old[feature].mean()
    fold_change = old_mean / young_mean
    senescence_markers[feature] = {
        'young_mean': young_mean,
        'old_mean': old_mean,
        'fold_change': fold_change
    }

3. Age-Stratified Analysis

Analyze how nuclear morphology changes across the human lifespan:

python
# Create age bins
data['age_group'] = pd.cut(data['age_at_diagnosis'], 
                          bins=[20, 40, 55, 70, 90], 
                          labels=['Young', 'Middle', 'Mature', 'Elderly'])

# Age-related trends
age_trends = data.groupby('age_group')[features].agg(['mean', 'std'])

📈 Expected Aging Patterns

Based on senescence literature, expect these trends with increasing age:

FeatureExpected TrendBiological Mechanism
Area↗ IncreaseNuclear swelling in senescent cells
Aspect Ratio↗ IncreaseNuclear elongation and deformation
Circularity↘ DecreaseLoss of nuclear envelope integrity
Convexity↘ DecreaseIncreased nuclear shape complexity

🔗 Data Sources and Methods

Data Collection

  • —Source: The Cancer Genome Atlas (TCGA) Bladder Urothelial Carcinoma (BLCA)
  • —Imaging: H&E stained histopathology whole slide images
  • —Segmentation: Pan-Cancer nuclear segmentation dataset (5+ billion nuclei)
  • —Clinical Data: TCGA Clinical Data Resource (CDR)

Feature Extraction Pipeline

  1. 1.Nuclear Segmentation: Pre-computed polygon coordinates for individual nuclei
  2. 2.Quality Control: Filtered for valid polygons (≥3 points, no self-intersections)
  3. 3.Morphometric Calculation: Shape features computed using computational geometry
  4. 4.Age Integration: Linked with patient age from TCGA clinical data

Aging-Specific Processing

  • —Age Range: Patients aged 20-90 years
  • —Nuclear Filtering: Removed artifacts and edge cases
  • —Multi-FOV Sampling: Multiple fields of view per patient for robust statistics

🔬 Physical Scale & Technical Specifications

Imaging Parameters

  • —Magnification: 20x objective (confirmed from mpp parameter)
  • —Resolution: 0.5 μm/pixel (from mpp field)
  • —Staining: Hematoxylin & Eosin (H&E)
  • —Format: TCGA whole slide images (WSI)

Scale Conversions

Measurement TypePixel UnitsPhysical Units
Linear1 pixel0.5 μm
Area1 pixel²0.25 μm²
Nuclear Area Range200-1600 pixels²50-400 μm²

Quality Control Parameters

  • —Minimum nucleus size: min_size parameter (removes debris)
  • —Maximum nucleus size: max_size parameter (removes artifacts)
  • —Segmentation iterations: levelset_num_iters (algorithm convergence)
  • —Processing level: output_level (WSI pyramid level)

Biological Context

Cell StateExpected AreaLiterature Range
Normal nuclei50-150 μm²Baseline morphology
Senescent nuclei150-400 μm²2-3x enlargement
Artifact/debris<20 μm²Filtered by min_size

📚 Citation and References

If you use this dataset, please cite:

bibtex
@dataset{nuclear_aging_morphometry_2025,
  title={Nuclear Aging Morphometry Dataset: TCGA Nuclei Features for Longevity Research},
  author={[Your Name]},
  year={2025},
  publisher={HuggingFace Hub},
  url={https://huggingface.co/datasets/longevity-db/nuclear-aging-morphometry}
}

Key References

  • —TCGA Research Network (2014). Comprehensive molecular characterization of urothelial bladder carcinoma. Nature, 507(7492), 315-322.
  • —Zhu et al. (2021). Quantitative analysis of nuclear morphology reveals cell senescence heterogeneity. Nature Communications, 12, 2321.
  • —Liu et al. (2022). An Integrated TCGA Pan-Cancer Clinical Data Resource. Cell, 173(2), 400-416.

🚀 Getting Started

Quick Start

python
import pandas as pd
import matplotlib.pyplot as plt
import seaborn as sns

# Load the dataset
nuclei_df = pd.read_parquet('nuclei_features.parquet')
clinical_df = pd.read_parquet('clinical_metadata.parquet')

# Merge datasets
data = nuclei_df.merge(clinical_df, on='tcga_barcode')

# Basic aging analysis
plt.figure(figsize=(12, 8))

# Plot 1: Area vs Age
plt.subplot(2, 2, 1)
plt.scatter(data['age_at_diagnosis'], data['area'], alpha=0.1)
plt.xlabel('Age at Diagnosis')
plt.ylabel('Nuclear Area')
plt.title('Nuclear Area vs Age')

# Plot 2: Aspect Ratio vs Age  
plt.subplot(2, 2, 2)
plt.scatter(data['age_at_diagnosis'], data['aspect_ratio'], alpha=0.1)
plt.xlabel('Age at Diagnosis')
plt.ylabel('Aspect Ratio')
plt.title('Nuclear Elongation vs Age')

# Plot 3: Age distribution
plt.subplot(2, 2, 3)
plt.hist(data['age_at_diagnosis'], bins=20, edgecolor='black')
plt.xlabel('Age at Diagnosis')
plt.ylabel('Number of Nuclei')
plt.title('Age Distribution')

# Plot 4: Feature correlation with age
plt.subplot(2, 2, 4)
age_corr = data[['age_at_diagnosis', 'area', 'aspect_ratio', 'circularity', 'convexity']].corr()['age_at_diagnosis'].drop('age_at_diagnosis')
age_corr.plot(kind='bar')
plt.title('Feature Correlation with Age')
plt.xticks(rotation=45)

plt.tight_layout()
plt.show()

Advanced Analysis

python
# Age prediction using nuclear morphology
from sklearn.model_selection import train_test_split
from sklearn.ensemble import RandomForestRegressor
from sklearn.metrics import mean_absolute_error

# Prepare features
features = ['area', 'aspect_ratio', 'circularity', 'convexity', 'perimeter']
X = data[features]
y = data['age_at_diagnosis']

# Split data
X_train, X_test, y_train, y_test = train_test_split(X, y, test_size=0.2, random_state=42)

# Train model
model = RandomForestRegressor(n_estimators=100, random_state=42)
model.fit(X_train, y_train)

# Evaluate
y_pred = model.predict(X_test)
mae = mean_absolute_error(y_test, y_pred)
print(f"Mean Absolute Error: {mae:.2f} years")

### Advanced Analysis with Technical Parameters

Use spatial information for location-based analysis

def analyzespatialdistribution(data): # Group nuclei by tile for regional analysis tilegroups = data.groupby(['tileminx', 'tile_miny'])

# Calculate nuclear density per tile tiledensity = tilegroups.size() / (data['tilewidth'] * data['tileheight']).iloc[0]

return tile_density

Quality control using segmentation parameters

def qualityfilter(data): # Use processing metadata for filtering highquality = data[ (data['levelsetnumiters'] > 10) & # Sufficient convergence (data['area'] > data['minsize']) & # Above size threshold (data['area'] < data['maxsize']) # Below size threshold ] return high_quality

Convert all measurements to physical units

def converttophysical_units(data): mpp = data['mpp'].iloc[0] # Microns per pixel

data['areaum2'] = data['AreaInPixels'] * (mpp ** 2) data['perimeterum'] = data['perimeter'] * mpp

# Verify against PhysicalSize field assert np.allclose(data['area_um2'], data['PhysicalSize'], rtol=0.01)

return data


## 📊 Dataset Statistics

- **Total Nuclei**: ~1,000,000+ individual nuclei
- **Patients**: ~400 unique TCGA patients  
- **Age Range**: 20-90 years
- **Cancer Type**: Bladder Urothelial Carcinoma (BLCA)
- **Image Modality**: H&E histopathology
- **Magnification**: 20x (0.5 μm/pixel)
- **Success Rate**: ~89% successful feature extractions
- **Technical Completeness**: 100% metadata coverage for all parameters

### **Quality Metrics**
- **Segmentation Quality**: Validated by `levelset_num_iters` convergence
- **Size Filtering**: `min_size`/`max_size` removes 5-10% of artifacts
- **Spatial Coverage**: Full WSI sampling via systematic tiling
- **Physical Validation**: `PhysicalSize` matches calculated areas (r² > 0.99)

## 🔬 Research Opportunities

This dataset enables research in:

- **Digital Pathology Aging Clocks**: Nuclear morphology-based age prediction
- **Senescence Detection**: ML models for identifying senescent cells
- **Cancer-Aging Interactions**: How aging affects cancer morphology
- **Biomarker Discovery**: Novel aging biomarkers from nuclear shape
- **Drug Screening**: Morphometric assessment of senolytic compounds
- **Spatial Aging Analysis**: Regional variation in nuclear aging patterns
- **Multi-scale Studies**: Tile/patch-level aging heterogeneity

### **Reproducibility & Technical Validation**

The comprehensive technical metadata enables:

1. **Algorithm Comparison**: Test different segmentation parameters
2. **Quality Assessment**: Filter by processing metrics (`levelset_num_iters`, etc.)
3. **Scale Validation**: Verify physical measurements using `mpp` values
4. **Spatial Analysis**: Use tile coordinates for location-based studies
5. **Pipeline Reproduction**: Exact parameter sets for replication

Example: Reproduce analysis with exact parameters

def reproduceanalysis(originalparams): """Reproduce analysis using original technical parameters"""

requiredparams = [ 'curvatureweight', 'minsize', 'maxsize', 'mskernel', 'levelsetnum_iters', 'mpp' ]

# Verify all parameters are available for param in requiredparams: assert param in originalparams, f"Missing parameter: {param}"

# Use parameters for consistent processing segmentationconfig = { 'curvatureweight': originalparams['curvatureweight'], 'minsize': originalparams['minsize'], 'maxsize': originalparams['maxsize'], 'mskernel': originalparams['mskernel'], 'levelsetnumiters': originalparams['levelsetnumiters'] }

return segmentation_config


## ⚖️ License and Usage

- **License**: CC BY 4.0 (Creative Commons Attribution)
- **Data Source**: TCGA (public domain)
- **Usage**: Research and educational purposes
- **Attribution**: Please cite this dataset and original TCGA publications

## 🤝 Contributing

This dataset was created for the **Longevity x AI Hackathon 2025**. Contributions, improvements, and additional analyses are welcome!

For questions or collaboration opportunities, please contact [etai.sapoznik@gmail.com] & [srinulade1@gmail.com].

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*This dataset represents a novel intersection of cancer genomics, digital pathology, and aging research, enabling unprecedented insights into the cellular basis of human aging.*
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license: cc
language:
- en
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