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This package provides functions to train, predict, and evaluate a Differentiable Loop Extrusion Model (dLEM) on HiC/Micro-C experiments. Take chromatin conformation data in (m)cool format and calculate L and R cohesin rate parameters.

_{Upper triangle: observed Micro-C. Lower triangle: dLEM's prediction from the fitted L/R tracks shown alongside.}

Requires Python 3.11–3.13 pip install dlem-jax

pip install git+https://github.com/chikinalab/dLEM.git

Refer to the Installation section in the documentation for more information and how to contribute.

dLEM

dLEM: differentiable Loop Extrusion Model. Fits L/R extrusion-barrier tracks to a single chromosome/region and reports mse/corr (+ optional CTCF alignment / plot).

Usage:

$ dlem [OPTIONS] DNA_INTS OUTPUT_LOCATION

Arguments:

• DNA_INTS: Path to a .cool file, or a .mcool file (use --resolution) [required]
• OUTPUT_LOCATION: Output directory, will be created if not existing [required]

Options:

• -c, --chrom TEXT: Chromosome to load (dlem.load_band's chrom) [required]
• -res, --resolution INTEGER: Bin resolution in bp [required]
• -w, --width INTEGER: Band depth (diagonals) to load [default: 200]
• --train-to INTEGER: Diagonals to fit (default: --width)
• -s, --slowdown FLOAT: dLEM slowdown constant (per-bin) [default: 0.025]
• --importance-power FLOAT: Within-diagonal emphasis on high-mass bins [default: 0.0]
• --diag-weight-power FLOAT: Between-diagonal weighting by mass^power [default: 1.0]
• --n-opt INTEGER: Adam optimization steps [default: 1500]
• --monitor TEXT: Checkpoint to select: mse|corr|loss|symm|symm2 [default: symm2]
• --ctcf-tsv PATH: Comp-table TSV (dlem.load_ctcf_tsv format) to report CTCF alignment against
• --plot: Save a data-vs-prediction PNG (prediction.png)
• --plot-start INTEGER: Plot window start (bins) [default: 0]
• --plot-span INTEGER: Plot window span (bins); default: --train-to
• -v, --verbose: Print optimization progress
• --help: Show this message and exit

This is a single-chromosome/region tool -- it does not do genome-wide batch fitting, bigWig track output, or predicted-.cool output; use the dlem library directly (see docs/quick_start.ipynb) for anything beyond one region.

Example (against the bundled example data):

$ dlem docs/data/example_chr10.cool /tmp/out \
    --chrom ref_region --resolution 10000 --width 700 --train-to 200 \
    --ctcf-tsv docs/data/example_ctcf.tsv --plot --plot-span 200

--ctcf-tsv reports how well the fitted barrier strength, (1-L)+(1-R), lines up with independent CTCF ChIP-seq signal at the same locus:

docker run ghcr.io/dborgesr/dlem:latest

git clone https://github.com/chikinalab/dLEM.git

pixi install -e

docker-compose build

docker-compose up --watch

If you use dLEM or any of its language bindings in your research, please cite the following publication:

Tina Subic, Ali Tuğrul Balcı, Kristina Perevoshchikova, Diego Borges-Rivera, Jieni Hu, Geoffrey Fudenberg, Jacqueline Dresch, Maria Chikina. Mechanistic Genome Folding at Scale through the Differentiable Loop Extrusion Model. Biorxiv, https://www.biorxiv.org/content/10.1101/2025.10.17.682904v2

@article{dlem,
    author = {Tina Subic and Ali Tuğrul Balcı and Kristina Perevoshchikova and Diego Borges-Rivera and Jieni Hu and Geoffrey Fudenberg and Jacqueline Dresch and Maria Chikina},
    title = "{dlem: diffrentiable loop extrusion model for chromatin looping data}",
    journal = {Biorxiv},
    volume = {40},
    number = {7},
    pages = {btae408},
    year = {2024},
    month = {06},
    issn = {1367-4811},
    doi = {10.1101/2025.10.17.682904},
    url = {https://doi.org/10.1101/2025.10.17.682904},
    eprint = {https://www.biorxiv.org/content/10.1101/2025.10.17.682904v2.full.pdf},
}