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SigMA2 - Mutational Signature Analysis in Python

SigMA2 is the Python version of SigMA, a tool developed to detect mutational Signature 3, which is associated with homologous recombination (HR) deficiency. It supports hybrid capture panels, whole-exome, and whole-genome sequencing (WGS) data. While traditional signature analysis tools struggle with data containing few single nucleotide variants (SNVs), SigMA2 is designed to perform well in such settings.

Installation

From PyPI (Recommended)

SigMA2 is currently an alpha pre-release, so --pre is required:

pip install --pre sigma2

Requires Python 3.9-3.12. The upper bound comes from a transitive dependency (pyranges -> ncls), which publishes no wheels for 3.13 or newer.

One dependency, sorted-nearest, is source-only on every Python version and is compiled during install, so a working C toolchain is needed (build-essential on Debian/Ubuntu, base-devel on Arch, Xcode command line tools on macOS).

From Source

git clone https://github.com/sigscape/SigMA2.git
conda env create -f ./SigMA2/environment.yml
conda activate sigmapy310
pip install -e ./SigMA2

Reference data

The package itself ships everything a run needs in the way of models: the data store, the SigMA v1 classifiers, and the panel definitions. Bulk reference data (germline VCFs and repeat regions, ~1.4 GB) is downloaded on demand instead:

sigma2 data list          # what exists and what is installed
sigma2 data fetch --all   # download everything
sigma2 data verify        # re-check checksums
sigma2 info               # versions, data directory, disk usage

Files land in a per-user data directory; set $SIGMA2_DATA_DIR to override it, which is the usual choice on a cluster where one pre-seeded copy is shared.

Reference genomes are separate and larger (~3 GB each): sigma2 data genome hg19.

Access note. Until the accompanying paper is published, the bulk data lives in a private repository. sigma2 data fetch therefore needs GitHub credentials with access to it — either run gh auth login, or set SIGMA2_GITHUB_TOKEN. Without access the fetch fails with a 404; the code itself is fully functional, and any data you already hold can be used by pointing $SIGMA2_DATA_DIR at it. Please contact the authors (below) to request access.

Quick Start

Follow these Jupyter Notebooks in numerical order to get started with SigMA2 and its built-in functions!

Documentation & Further Information

Find more here

Contact

Requests for use of the Software for or on behalf of for-profit entities or for any commercial purposes, please contact:

Office of Technology Development Harvard University Smith Campus Center, Suite 727E 1350 Massachusetts Avenue Cambridge, MA 02138 USA Telephone: (617) 495-3067 E-mail: otd@harvard.edu

Citation

If you use SigMA2 in your work, please cite the original SigMA publication as follows:

Detecting the mutational signature of homologous recombination deficiency in clinical samples <br/> Doga C. Gulhan, Jake June-Koo Lee, Giorgio E. M. Melloni, Isidro Cortés-Ciriano & Peter J. Park <br/> Nature Genetics (2019)<br/> https://doi.org/10.1038/s41588-019-0390-2