Horizyn: Contrastive Learning for Enzyme-Reaction Matching

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Official implementation of the Horizyn model for matching reactions and enzymes. Register here to query Horizyn interactively or via the API.

Overview

Horizyn is a dual-encoder contrastive learning model that learns to match enzymatic reactions with their catalyzing proteins. The model uses:

• Reaction Encoder: Concatenated RDKit+ (structural) and DRFP fingerprints → MLP
• Protein Encoder: Pre-computed T5 embeddings → MLP
• Loss: Maximum Likelihood Noise Contrastive Estimation (MLNCE)
• Embeddings: 512-dimensional normalized outputs for both encoders

Quick Start

Installation

Install dependencies with UV (recommended):

uv sync

Or with pip:

pip install -e .

Download Dataset

Download the SOTA dataset (~1GB):

python scripts/download_data.py

Train the Model

Train the SOTA model (requires ~16GB RAM, single GPU with 16GB+ VRAM):

python train.py --config configs/sota.yaml

Evaluate the Model

Evaluate a trained model checkpoint on the test set:

python scripts/evaluate.py --checkpoint checkpoints/epoch=99-step=XXXXX.ckpt

The evaluation script computes retrieval metrics (Top-K hit rates, MRR) on the held-out test set. Checkpoints are saved during training to the checkpoints/ directory.

Hardware Requirements

• RAM: 8GB minimum (4GB for data loaded entirely in memory)
• GPU: Single NVIDIA GPU with 16GB+ VRAM (e.g., T4, A10G, V100)
• Disk: 20GB free space for dataset and checkpoints
• Platform: Linux x86_64 with CUDA 12.1

Project Structure

horizyn/
├── horizyn/                    # Main package
│   ├── model.py               # DualContrastiveModel, MLP
│   ├── lightning_module.py    # Training loop logic
│   ├── data_module.py         # Data loading orchestration
│   ├── config.py              # Configuration management
│   ├── losses.py              # MLNCE loss function
│   ├── metrics.py             # Retrieval metrics
│   ├── datasets/              # Dataset classes
│   │   ├── base.py           # Base dataset abstractions
│   │   ├── collection.py     # Dataset composition utilities
│   │   ├── csv.py            # CSV dataset loader
│   │   ├── hdf5.py           # HDF5 embedding loader
│   │   ├── transform.py      # Data transformations
│   │   └── fingerprints/     # Chemical fingerprint generation
│   │       ├── base.py       # Fingerprint base class
│   │       ├── rdkit_plus.py # RDKit structural fingerprints
│   │       └── drfp.py       # Differential reaction fingerprints
│   ├── chemistry/             # Chemistry utilities
│   │   └── standardizer.py   # SMILES standardization
│   └── utils/                 # Utility functions
│       ├── cache.py          # In-memory caching
│       └── collate.py        # Batch collation
├── configs/                   # Training configurations
│   ├── sota.yaml             # SOTA configuration
│   └── nano.yaml             # Small test configuration
├── scripts/                   # Helper scripts
│   └── download_data.py      # Dataset download
├── train.py                   # Main training entry point
└── tests/                     # Test suite

Model Architecture

The Horizyn model uses a dual-encoder architecture:

• Query Encoder (Reactions): 2048-dim fingerprints → 4096-dim hidden → 512-dim embedding
• Target Encoder (Proteins): 1024-dim T5 embeddings → 4096-dim hidden → 512-dim embedding
• Loss Function: MLNCE with temperature parameter (β=10.0)

Citation

If you use this code in your research, please cite:

@article{horizyn2025,
  title = {Dual-encoder contrastive learning accelerates enzyme discovery},
  author = {Rocks, Jason W. and Truong, Dat P. and Rappoport, Dmitrij and Maddrell-Mander, Sam and Martin-Alarcon, Daniel A. and Lee, Toni and Crossan, Steve and Goldford, Joshua E.},
  journal = {bioRxiv}
  year = {2025},
  doi = {10.1101/2025.08.21.671639},
}

License

This code is licensed under PolyForm Noncommercial License 1.0.0.

• ✅ Noncommercial use: Free to use and modify for noncommercial purposes
• ✅ Research and education: Permitted for academic, research, and educational purposes
• ❌ Commercial use: Prohibited without separate commercial licensing
• 📧 Commercial inquiries: info@dayhofflabs.com

See LICENSE for full terms or visit https://polyformproject.org/licenses/noncommercial/1.0.0

Contributing

This repository is maintained by Dayhoff Labs. For questions or issues, please open a GitHub issue.