SigProfilerClusters analyzes inter-mutational distances (IMD) between SNV-SNV and INDEL-INDEL mutations, separating them into clustered and non-clustered groups on a sample-dependent basis. Clustered SNVs are further subclassified into doublet base substitutions (DBS), multi-base substitutions (MBS), omikli, and kataegis events. The tool uses SigProfilerSimulator to build a per-sample background model and applies a regionally corrected IMD threshold to identify mutations unlikely to have co-occurred by chance.
Detailed documentation can be found at https://sigprofilersuite.github.io/SigProfilerClusters.
Install the current stable PyPI version of SigProfilerClusters:
$ pip install SigProfilerClusters
Install your desired reference genome (available genomes: GRCh37, GRCh38, mm9, mm10):
$ python
from SigProfilerMatrixGenerator import install as genInstall
genInstall.install('GRCh37')First, generate a background model using SigProfilerSimulator (minimum 100 simulations recommended):
from SigProfilerSimulator import SigProfilerSimulator as sigSim
sigSim.SigProfilerSimulator(project, project_path, genome, contexts=["288"], chrom_based=True, simulations=100)Then, partition mutations into clustered and non-clustered sets:
from SigProfilerClusters import SigProfilerClusters as hp
hp.analysis(project, genome, contexts, simContext, input_path)Results are placed under [project_path]/output/clustered/ and [project_path]/output/nonClustered/. Visualizations are found under [project_path]/output/plots/.
Bergstrom EN, Kundu M, Tbeileh N, Alexandrov LB. Examining clustered somatic mutations with SigProfilerClusters. Bioinformatics. 2022;38(13):3470–3473. https://doi.org/10.1093/bioinformatics/btac335
Bergstrom EN, Luebeck J, Petljak M, et al. Mapping clustered mutations in cancer reveals APOBEC3 mutagenesis of ecDNA. Nature. 2022;602:510–517. https://doi.org/10.1038/s41586-022-04398-6
For questions, support requests, or bug reports, please contact the SigProfilerSuite team via GitHub issues or by email at contact@sigprofilersuite.org.