damuta 1.0.0

Dirichlet allocation of mutations in cancer genomes

Dirichlet Allocation of MUTAtions in cancer

Damage and Misrepair Signatures: Compact Representations of Pan-cancer Mutational Processes

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DAMUTA signature definitions

• 18 Damage signatures
• 6 Misrepair signatures

nb. internally these signatures are referred to by their symbols in the graphical model: eta and phi respectively.

Features

• Separately model damage and misrepair processes
• Estimate activities of DAMUTA signatures
• Fit new Damage- and Misrepair-signatures denovo

Model

Installation

DAMUTA is built on pymc3 - which depends on theano. To use theano with gpu, you will need to install pygpu. The simplest way to do so is via conda.

conda create -f damuta_env.yml

from pipy

pip install damuta

From Environment File

Clone this repo git clone https://github.com/morrislab/damuta

conda env create -f damuta_env.yml
conda activate damuta
pip install -e .

theanorc

To use the GPU, ~/.theanorc should contain the following:

[global]
floatX = float64
device = cuda

Otherwise, device will default to CPU.

Data

Some files are omitted from this repository due to access restrictions. access can be requested from the corresponding sources:

• PCAWG/ICGC
• Hartwig
• Genomics England

Data for reproducing manuscript figures

Unrestricted-access data and certain useful intemediate files are also available via can be downloaded from zenodo

To download and organize these data:

# in top-level directory
wget  https://zenodo.org/records/15685052/files/damuta_zenodo.zip
unzip damuta_zenodo

mv damuta_zenodo/data/* manuscript/data
mv damuta_zenodo/figure_data/* manuscript/results/figure_data

# clean up now-empty directories
rmdir damuta_zenodo/data damuta_zenodo/figure_data damuta_zenodo

Some useful public data

file name	info	source
COSMIC_v3.2_SBS_GRCh37.csv	COSMIC database
icgc_sample_annotations_summary_table.txt	sample annotations used by PCAWG heterogeneity & evolution working group	ICGC data portal
PCAWG_sigProfiler_SBS_signatures_in_samples	counts of mutations attributed to each signature for PCAWG samples	syn11738669.7
pcawg_counts.csv	mutation type counts in PCAWG samples	Derived from syn7357330
pcawg_cancer_types.csv	sample annotations used in Jiao et. al	Adapted from z-scores file
gel_clinical_ann.csv	tumour type annotations for 18640 samples (ICGC, HMF, GEL)	Adapted from Degasperi et. al table S6
gel_counts.csv	mutation type counts for 18640 samples (ICGC, HMF, GEL)	Adapted from Degasperi et. al table S7

Citation

@misc{harrigan_damage_2025,
	title = {Damage and {Misrepair} {Signatures}: {Compact} {Representations} of {Pan}-cancer {Mutational} {Processes}},
	copyright = {© 2025, Posted by Cold Spring Harbor Laboratory. This pre-print is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), CC BY-NC 4.0, as described at http://creativecommons.org/licenses/by-nc/4.0/},
	shorttitle = {Damage and {Misrepair} {Signatures}},
	url = {https://www.biorxiv.org/content/10.1101/2025.05.29.656360v1},
	doi = {10.1101/2025.05.29.656360},
	language = {en},
	urldate = {2025-06-02},
	publisher = {bioRxiv},
	author = {Harrigan, Caitlin F. and Campbell, Kieran and Morris, Quaid and Funnell, Tyler},
	month = jun,
	year = {2025},
}