Mimosa

Mimosa is a Python 3.12+ package and command-line tool for DNA motif comparison. It supports PWM/PFM, BaMM, SiteGA, Dimont, Slim, and precomputed score profiles. Mimosa compares heterogeneous motif models through their behavior on the same DNA sequences rather than by forcing their internal representations into a common matrix.

Background

Transcription factors (TFs) are key regulators of gene expression. They bind specific DNA sequences, termed transcription factor binding sites (TFBSs), located in gene regulatory regions. Because TFBSs are highly variable, they are typically described using motifs, which capture the nucleotide preferences of a TF across a range of binding sites. The position weight matrix (PWM) is the de facto standard motif model, assuming independence between positions and additive nucleotide contributions. However, numerous studies have demonstrated the presence of dependencies between positions within TFBSs. To account for such dependencies, alternative models have been proposed, including Markov-based approaches (BaMM, InMoDe, Dimont, Slim, MODER2), discriminative methods (SiteGA), and deep learning models (DeepBind, DeepGRN, BERT-TFBS). However, a mature ecosystem of databases and tools has been developed primarily for PWMs, including motif comparison methods that are critical for result interpretation. Comparison of alternative motif models usually requires their conversion into PWMs, which inevitably leads to loss of information about positional dependencies. At present, no universal tool exists for their direct comparison. Mimosa (Model-Independent Motif Similarity Assessment) addresses this gap by evaluating motif similarity based on functional behavior, namely the scores models assign to DNA sequences rather than their internal parameters.

Mimosa uses the following profile comparison pipeline:

1. Scan sequences by motifs to obtain score profiles.
2. Convert raw scores to empirical -log10(ERR) values, where ERR is the expectation recognition rate, optionally using a separate background sequence set for calibration.
3. Select one strict best anchor per non-empty sequence when min_logerr <= 0, or all anchors with -log10(ERR) >= min_logerr for a positive threshold.
4. Compare site-centered windows over shifts and the four strand orientations.
5. Return the highest-scoring alignment, its offset, orientation, and number of contributing sites.

See Method and Statistics for metric definitions, statistical significance, and references.

Supported Models

Installation

Mimosa requires Python 3.12 or newer.

uv sync

For a regular local installation:

python -m pip install .

CLI

Compare two PWM models on a FASTA batch:

uv run mimosa profile examples/foxa2.meme examples/gata2.meme \
  --model1-type pwm --model2-type pwm \
  --fasta examples/foreground.fa --metric co

Compare precomputed score profiles:

uv run mimosa profile examples/scores_1.fasta examples/scores_2.fasta \
  --model1-type scores --model2-type scores --metric cosine

Build and use an empirical null distribution:

uv run mimosa build-null examples/ \
  --model-type pwm --output output/null_bundle \
  --fasta examples/foreground.fa --num-samples 2000 --seed 127

uv run mimosa profile examples/foxa2.meme examples/gata2.meme \
  --model1-type pwm --model2-type pwm \
  --fasta examples/foreground.fa \
  --pvalue --null-distribution output/null_bundle

Manage the optional prepared-profile cache:

uv run mimosa cache clear --cache-dir .mimosa-cache

Successful profile results are JSON on stdout. Diagnostics and errors are written to stderr. Run uv run mimosa --help for the complete CLI reference.

Python API

from mimosa import compare, read_fasta, read_model

query = read_model("examples/foxa2.meme")
target = read_model("examples/gata2.meme")
sequences, names = read_fasta("examples/foreground.fa")

result = compare(query, target, sequences, metric="co")
print(result.to_dict())

For repeated comparisons, prepare the query once:

from mimosa import compare_many, prepare_profile

prepared = prepare_profile(query, sequences)
results = compare_many(prepared, [target], sequences, metric="cosine")

The public API also includes scan, read_scores, select_sites, reconstruct_pfm, build_null, annotate_results, and write_model.

Documentation

• Python Documentation
• Python Quickstart
• Python API
• CLI Reference
• Supported Models and Formats
• Comparison Method and Statistics
• Custom Models and Readers
• Storage and Cache
• Data Layout and Coordinates

Development

Run the test suite with:

uv run pytest -q

License

MIT. See LICENSE.