Our tool is under active development and feedback is very much appreciated.

learnMSA2: deep protein multiple alignments with large language and hidden Markov models

Features

• aligns large numbers of protein sequences with state-of-the-art accuracy
• can utilize protein language models (--use_language_model) for significantly improved accuracy compared to state-of-the-art tools
• enables ultra-large alignment of millions of sequences
• GPU acceleration
• linear scaling with sequence count, does not require or build a guide tree
• memory efficient (depending on sequence length, aligning millions of sequences on a laptop is possible)
• visualize a profile HMM or a sequence logo of the consensus motif

Current limitations

• requires many sequences (in most cases starting at 1000, a few 100 might still be enough) to achieve high accuracy
• only for proteins
• increasingly slow for long proteins with a length > 1000 residues

Documentation

Find it here.

Installation

You have 3 options to install learnMSA.

Option 1: Singularity/Docker

We provide a hassle-free Docker image including everything you need to align on GPU with protein language model support.

This is the recommended and most stable way to install learnMSA.

singularity build learnmsa.sif docker://felbecker/learnmsa
singularity run --nv learnmsa.sif learnMSA

Running the container with --nv is required for GPU support.

Option 2: Conda/mamba and pip

1. Create a conda environment:

conda create -n learnMSA python=3.12
conda activate learnMSA

2. Install learnMSA (CUDA toolkit included):

pip install learnMSA

3. Additional installs for sequence weights (recommended!):

conda install -c conda-forge -c bioconda "python=3.12.*" mmseqs2

You may have to set up Bioconda channels. We pin the currently installed python executable to prevent installing newer mmseqs2 versions that would remove or alter.

4. Additional installs for language model support (recommended!):

pip install torch==2.6

5. (optional) Verify that TensorFlow and learnMSA are correctly installed:

python3 -c "import tensorflow as tf; print(tf.__version__, tf.config.list_physical_devices('GPU'))"
learnMSA -h

Option 3: Bioconda

conda create -c bioconda -n learnMSA learnMSA

This installs everything you need in a conda environment. However, due to the way TensorFlow is distributed via conda currently no GPU support is provided out of the box.

Therefore, a post install fix is needed:

conda activate learnMSA && pip install tensorflow[and-cuda]=="$(pip show tensorflow | grep ^Version: | awk '{print $2}')"

Using learnMSA for alignment

Recommended way to align proteins with learnMSA version >= 2.0.10:

learnMSA -i INPUT_FILE -o OUTPUT_FILE --use_language_model

Recommended way to align proteins with learnMSA version < 2.0.10:

learnMSA -i INPUT_FILE -o OUTPUT_FILE --use_language_model --sequence_weights

Without language model support (recommended for speed and for proteins with very high sequence similarity):

learnMSA -i INPUT_FILE -o OUTPUT_FILE

Note: If you installed learnMSA via docker/singularity, you have to run singularity run --nv learnmsa.sif learnMSA -i ...

Note 2: Since v2.0.10 the default behavior changed: Sequence weights are now used by default and the --sequence_weights option was removed. Instead, a --no_sequence_weights option exists to align without sequence weights (not recommended). Users that installed learnMSA via pip have to manually install mmseqs2 (conda is recommended, see above).

To output a pdf with a sequence logo alongside the msa, use --logo. For a fun gif that visualizes the training process, you can use --logo_gif (attention, slows down training and should not be used for real alignments).

Interactive notebook with visualization:

Run the notebooks learnMSA_demo.ipynb or learnMSA_with_language_model_demo.ipynb with juypter.

Benchmark:

Publications

Becker F, Stanke M. learnMSA2: deep protein multiple alignments with large language and hidden Markov models. Bioinformatics. 2024

Becker F, Stanke M. learnMSA: learning and aligning large protein families. GigaScience. 2022

$\text{Troubleshooting:}\{\backslash text\{\backslash color\{red\}Troubleshooting:\}\}$

Error:

tensorflow.python.framework.errors_impl.UnknownError: {{function_node __wrapped__Expm1_device_/job:localhost/replica:0/task:0/device:GPU:0}} JIT compilation failed.

Your root error is: TensorFlow libdevice not found

Fix:

Find nvvm directory: find / -type d -name nvvm 2>/dev/null

Expected outputs: <path>/nvvm

If there are multiple paths, choose the one matching your conda environment.

Run: export XLA_FLAGS=--xla_gpu_cuda_data_dir=<path>

Error:

ERROR: Flag 'minloglevel' was defined more than once (...)

Fix: pip install --no-deps --upgrade sentencepiece==0.1.99