The (current) purpose of this branch is for exploratory analysis

Cross-Pathogen PLM Embedding Analysis

This project uses protein language models (PLMs) to analyze evolutionary dynamics across multiple viral pathogens. The pipeline computes mutation-level embeddings, evolutionary velocity, and comparative metrics to understand patterns of viral evolution across pathogens with varying rates of adaptation.

Adaptive substitution rates are from Kistler & Bedford 2023: "An atlas of continuous adaptive evolution in endemic human viruses." Cell Host Microbe 31: 1-12.

Installation

Install dependencies with pip including PyTorch and transformers:

pip install -r requirements.txt

Workflow

The workflow is managed through Snakemake and processes multiple pathogens in parallel:

Run Full Pipeline

Process all configured pathogens through the complete analysis:

snakemake --cores all all_pathogens

Individual Steps

Run specific analysis steps:

# Download Nextstrain data only
snakemake --cores 1 data/pathogen/{pathogen}/auspice.json

# Compute embeddings only
snakemake --cores 4 results/pathogen/{pathogen}/node_embeddings.pkl

# Generate final summary
snakemake --cores 1 aggregate_pathogens

Pathogen-specific Analysis

To analyze specific pathogens:

# Single pathogen
snakemake --cores 4 results/cross_pathogen/sars_cov_2_spike/mutation_metrics.tsv

# Multiple pathogens
snakemake --cores 8 results/cross_pathogen/{influenza_h3n2_ha,rsv_a_g}/velocity.tsv

Available Datasets

The following pathogens are pre-configured in config/cross_pathogen_config.yaml:

• influenza_h3n2_ha: Influenza A/H3N2 HA1 protein (8.62 adaptive subs/year)
• influenza_h1n1pdm_ha: Influenza A/H1N1pdm HA1 protein (5.38 adaptive subs/year)
• norovirus_gii4_vp1: Norovirus GII.4 VP1 capsid protein (4.12 adaptive subs/year)
• cov_229e_s1: 229E coronavirus S1 protein (2.94 adaptive subs/year)
• rsv_a_g: RSV-A G protein (2.77 adaptive subs/year)
• rsv_b_g: RSV-B G protein (2.35 adaptive subs/year)
• influenza_vic_ha: Influenza B/Victoria HA1 protein (2.16 adaptive subs/year)
• oc43_a_s1: OC43 coronavirus S1 protein (2.12 adaptive subs/year)
• sars_cov_2_spike: SARS-CoV-2 Spike protein (?? adaptive subs/year)
• mumps_sh: Mumps SH protein (-0.17 adaptive subs/year)
• measles_n: Measles N protein (-0.62 adaptive subs/year, internal protein)

Configuration

Edit config/pathogen_config.yaml to configure pathogens and settings:

pathogens:
  sars_cov_2_spike:
    dataset: "https://nextstrain.org/ncov/gisaid/global/all-time"
    gene: "S"
    protein: "Spike"
    protein_coords: "S:1-1273"
    surface: true
    adaptive_subs_per_year: 0.4 # To Be Upadated
  
pipeline_settings:
  embedding_model: "facebook/esm2_t6_8M_UR50D"
  min_recurrence: 3
  batch_size: 100

Output Structure

results/cross_pathogen/
├── {pathogen}/
│   ├── node_embeddings.pkl       # PLM embeddings
│   ├── mutation_vectors.tsv      # Embedding space changes per mutation
│   ├── mutation_metrics.tsv      # Mutation-level statistics
│   └── velocity.tsv              # Evolutionary velocity per branch
└── summary/
    └── pathogen_summary.csv      # Cross-pathogen comparison

License

This repository is licensed under the MIT License. See the LICENSE file for details.