Hidden Markov models lead to higher resolution maps of mutation signature activity in cancer
Open Access
- 26 July 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Genome Medicine
- Vol. 11 (1), 1-12
- https://doi.org/10.1186/s13073-019-0659-1
Abstract
Knowing the activity of the mutational processes shaping a cancer genome may provide insight into tumorigenesis and personalized therapy. It is thus important to characterize the signatures of active mutational processes in patients from their patterns of single base substitutions. However, mutational processes do not act uniformly on the genome, leading to statistical dependencies among neighboring mutations. To account for such dependencies, we develop the first sequence-dependent model, SigMa, for mutation signatures. We apply SigMa to characterize genomic and other factors that influence the activity of mutation signatures in breast cancer. We show that SigMa outperforms previous approaches, revealing novel insights on signature etiology. The source code for SigMa is publicly available at https://github.com/lrgr/sigma.Keywords
This publication has 53 references indexed in Scilit:
- Signatures of mutational processes in human cancerNature, 2013
- An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancersNature Genetics, 2013
- DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegiseLife, 2013
- APOBEC3B is an enzymatic source of mutation in breast cancerNature, 2013
- Deciphering Signatures of Mutational Processes Operative in Human CancerCell Reports, 2013
- EMu: probabilistic inference of mutational processes and their localization in the cancer genomeGenome Biology, 2013
- Two Mechanisms Produce Mutation Hotspots at DNA Breaks in Escherichia coliCell Reports, 2012
- An integrated encyclopedia of DNA elements in the human genomeNature, 2012
- Clustered Mutations in Yeast and in Human Cancers Can Arise from Damaged Long Single-Strand DNA RegionsMolecular Cell, 2012
- Mutational Processes Molding the Genomes of 21 Breast CancersCell, 2012