ToxProt25: Analysis of ToxProt (2005-2025)

Comparative analysis of toxin proteins from ToxProt across 20 years of UniProtKB releases (2005-2025).

🎯 Project Overview

This project analyzes changes in toxin-related proteins across different UniProtKB snapshots:

• Taxonomic changes: Species representation and new taxa emergence
• Habitat patterns: Marine vs terrestrial protein family distributions
• Protein families: Classification and abundance changes
• GO-term analysis: Functional annotation comparisons
• PTM analysis: Post-translational modification patterns
• Curation insights: Protein family renamings and annotation improvements
• Protein space: 2D embedding visualization using ProtSpace

🚀 Setup

Installation

# Install dependencies
uv sync

Data Files

UniProtKB SwissProt DAT files (.dat) are not included due to size. Download them:

# Download all years (2005-2025)
uv run python src/data_processing/download_uniprot_releases.py

Files are saved to data/raw/ as {year}_sprot.dat.

🔬 Analysis Pipeline

1. Data Processing

Parse SwissProt DAT files (src/data_processing/parse_sprot_dat.py)

Extracts toxin entries matching: (taxonomy_id:33208) AND ((cc_tissue_specificity:venom) OR (keyword:KW-0800))

Features:

• Signal peptide processing for mature sequences
• Protein metadata extraction (names, families, length, mass)
• Functional annotations (tissue specificity, toxic dose)
• Post-translational modifications (MOD_RES, CARBOHYD, DISULFID, CROSSLNK, LIPID)
• Automatic PTM vocabulary download (ptmlist.txt)

Clean and enrich data (src/data_processing/clean_data.py)

• Standardize protein family names
• Generate FASTA files (full and mature sequences)
• Taxonomic enrichment (phylum, class, order, family, genus, species)
• Habitat classification (marine/terrestrial)

2. Comparative Analyses

All analysis scripts are in src/analysis/:

Analysis	Script	Outputs
Protein Families	analyze_protein_families.py	Distribution charts, length histograms
Taxonomic Changes	analyze_taxa.py	Taxa distribution, newcomers by order/family
Habitat Patterns	analyze_habitat.py	Marine vs terrestrial comparisons, Venn diagrams, heatmaps
PTMs	analyze_ptm.py	Modification type distributions and statistics
GO Terms	analyze_go_terms.py	Functional annotation comparisons
Protein Evidence	plot_protein_evidence_sankey.py	Evidence flow Sankey diagrams
Curation Tracking	generate_family_renaming_report.py	Family name change reports

3. ProtSpace Analysis

Generate protein embeddings and 2D visualizations (src/protspace/):

1. generate_fasta_for_embeddings.py - Prepare sequences
2. process_protspace.py - Generate embeddings (requires ProtSpace)
3. generate_plots.py - Create 2D visualizations
4. analyze_clustering.py - Clustering quality metrics

See src/protspace/README.md for details.

📊 Output Structure

data/
  ├── raw/           # Source data (habitat classifications, PTM vocabulary)
  ├── interim/       # Parsed SwissProt data
  └── processed/     # Cleaned datasets and ProtSpace embeddings
figures/             # All generated visualizations
notebook/            # Jupyter analysis notebooks
docs/                # Analysis summaries and notes

📝 Data Sources

• UniProtKB/SwissProt: Historical and current releases (.dat files)
• ToxProt: March 2025 export (202503_ToxProt.tsv)
• Habitat classification: Manual taxonomic curation (marine_terrestrial.json, habitat_detailed.json)