ProFam is an open-source toolkit for training, scoring, and generating protein sequences with protein family language models. It packages the ProFam-1 251M-parameter pfLM together with open training and inference workflows, a downloadable pretrained checkpoint, and an open dataset release for reproducible experimentation.

Installation

From PyPI

Install ProFam as a standard Python package:

uv pip install profam

or

pip install profam

From Source

If you want the full repository workflows, example data, and inference scripts:

git clone https://github.com/alex-hh/profam.git
cd profam
uv sync
profam download

Optional installs:

• Development tooling: uv sync --group dev
• FlashAttention 2: uv sync --extra flash-attn

If you run into CUDA or flash-attn issues, see Installation Details.

Quickstart

Verify the installed package

python -c "from profam import ProFam; print('ProFam ready')"

Download the pretrained model weights

The ProFam-1 model weights are hosted on Hugging Face and need to be downloaded before use (or they will be auto-downloaded on first use):

profam download

Python API

The recommended way to use ProFam programmatically:

from profam import ProFam

model = ProFam()  # loads checkpoint once (auto-downloads if needed)

# Generate sequences conditioned on family context
result = model.generate(
    prompt=["ACDEFGHIKLMNPQRSTVWY", "ACDEFGHIKLMNPQRSTVWF"],
    num_samples=10,
    top_p=0.95,
)
print(result.sequences)  # list of generated amino acid strings
print(result.scores)     # mean log-likelihood per sequence

# Score candidate sequences
result = model.score(
    sequences=["ACDEFGHIKLMNPQRSTVWY", "ACDEFGHIKLMNPQRSTVWF"],
    prompt=["ACDEFGHIKLMNPQRSTVWY"],  # conditioning context
)
print(result.scores)  # numpy array of mean log-likelihoods

# Iterative design loop
prompt = initial_sequences
for cycle in range(n_cycles):
    result = model.generate(prompt=prompt, num_samples=20, top_p=0.95)
    # ... evaluate with external tools ...
    prompt = initial_sequences + selected_sequences

CLI

profam generate -- --file_path family.fasta --num_samples 10
profam score -- --conditioning_fasta family.a3m --candidates_file variants.csv
profam download

Main Workflows

Workflow	Purpose	Command
Download checkpoint	Fetch the pretrained ProFam-1 checkpoint	profam download
Generate sequences	Sample new sequences from family prompts	profam generate -- --file_path ...
Score sequences	Score candidate sequences with family context	profam score -- --conditioning_fasta ...

Input Sequence Formats

ProFam supports:

• Unaligned FASTA for standard protein sequence inputs
• Aligned / MSA-style files such as A2M/A3M content with gaps and insertions

For profam-score-sequences, we recommend providing an aligned MSA file because sequence weighting is used to encourage diversity when subsampling prompt sequences. Even when aligned inputs are provided, the standard ProFam model converts them into unaligned gap-free sequences before the forward pass.

During preprocessing:

• gaps (- and alignment-like .) are removed
• lowercase insertions are converted to uppercase
• U -> C and O -> K
• remaining out-of-vocabulary characters map to [UNK] only when allow_unk=true

Training

Training is handled via Hydra configs and is intended for development from the source repository (not via pip-installed commands).

Run a lightweight example

configs/experiment/train_profam_example.yaml is configured to run on the bundled example data:

uv run python -m profam.train experiment=train_profam_example logger=null_logger

Train with the ProFam-Atlas dataset

Training data for ProFam can be downloaded from:

• Zenodo: ProFam Atlas Dataset

The default configuration in configs/train.yaml is compatible with the latest ProFam-Atlas release:

uv run python -m profam.train

Resources

• bioRxiv preprint
• Hugging Face: ProFam-1 checkpoint
• Zenodo: ProFam Atlas Dataset
• GitHub repository

Citation

If you use ProFam in your work, please cite the preprint:

@article{wells2025profam,
  title = {ProFam: Open-Source Protein Family Language Modelling for Fitness Prediction and Design},
  author = {Wells, Jude and Hawkins Hooker, Alex and Livne, Micha and Lin, Weining and Miller, David and Dallago, Christian and Bordin, Nicola and Paige, Brooks and Rost, Burkhard and Orengo, Christine and Heinzinger, Michael},
  journal = {bioRxiv},
  year = {2025},
  doi = {10.64898/2025.12.19.695431},
  url = {https://www.biorxiv.org/content/10.64898/2025.12.19.695431v1}
}

Installation Details

CPU-only installation

uv sync
uv pip install torch --index-url https://download.pytorch.org/whl/cpu

FlashAttention 2

We recommend installing FlashAttention 2 for faster scoring and generation. For training, it is strongly recommended because ProFam uses sequence packing with batch_size=1 and no padding.

If you need to train without Flash Attention, update the configuration to set data.pack_to_max_tokens=null.

uv sync --extra flash-attn
python -c "import flash_attn; print(flash_attn.__version__)"

Troubleshooting: conda fallback

If a matching flash-attn wheel is unavailable and a source build is required, this conda-based fallback is often the easiest route:

conda create -n pfenv python=3.11 -y
conda activate pfenv

conda install -c conda-forge ninja packaging -y
conda install -c nvidia cuda-toolkit=12.4 -y

pip install profam

# install a CUDA-enabled PyTorch build (adjust CUDA version/index-url to match your setup)
pip install torch==2.5.1+cu121 torchvision==0.20.1+cu121 --index-url https://download.pytorch.org/whl/cu121

pip install setuptools wheel packaging psutil numpy
pip install flash-attn==2.5.6 --no-build-isolation

python -c "import flash_attn; print(flash_attn.__version__)"

Development

We're using pre-commit to format code and pytest to run tests.

Pull requests will automatically have pre-commit and pytest run on them and will only be approved once these checks are all passing

Before submitting a pull request, run the checks locally with:

uv run --group dev pre-commit run --all-files

and

uv run --group dev pytest -k 'not example'

Pull requests adding complex new features or making any significant changes or additions should be accompanied with associated tests in the tests/ directory.

Concepts

Data loading

ProFam uses text memmap datasets for fast random access over large corpora:

• profam/data/text_memmap_datasets.py: generic memory-mapped line access + index building (*.idx.{npy,info})
• profam/data/builders/family_text_memmap_datasets.py: ProFam-Atlas-specific datasets built on top of the memmap layer

ProFam-Atlas on-disk format (.mapping / .sequences)

The ProFam-Atlas dataset is distributed as paired files:

• *.mapping: family id + indices into one or more *.sequences files
  • Format:
    • Line 1: >FAMILY_ID
    • Line 2+: sequences_filename:idx0,idx1,idx2,...
  • Important: *.mapping files must not have a trailing newline at end-of-file.
• *.sequences: FASTA-like accessions + sequences
  • Format (repeated):
    • >ACCESSION ...
    • SEQUENCE
  • Important: *.sequences files should have a final trailing newline.

See README_ProFam_atlas.md for examples and additional details.

How it’s loaded

At a high level, training loads one protein family at a time by:

1. Reading a family record from MappingProteinFamilyMemmapDataset (a memmapped *.mapping dataset)
2. Fetching the referenced sequences from SequencesProteinFamilyMemmapDataset (memmapped *.sequences files)
3. Building a ProteinDocument and preprocessing it (see profam/data/processors/preprocessing.py)
4. Encoding with ProFamTokenizer and forming batches (optionally with packing)

Converting FASTA → text memmap

If you have a directory of per-family FASTA files and want to create *.mapping / *.sequences files for training, see:

• data_creation_scripts/fasta_to_text_memmap.py