decompTumor2Sig: identification of mutational signatures active in individual tumors

Abstract

Background The somatic mutations found in a tumor have in most cases been caused by multiple mutational processes such as those related to extrinsic carcinogens like cigarette smoke, and those related to intrinsic processes like age-related spontaneous deamination of 5-methylcytosine. The effect of such mutational processes can be modeled by mutational signatures, of which two different conceptualizations exist: the model introduced by Alexandrov et al., Nature 500:415–421, 2013, and the model introduced by Shiraishi et al., PLoS Genetics 11(12):e1005657, 2015. The initial identification and definition of mutational signatures requires large sets of tumor samples.

Results Here, we present decompTumor2Sig, an easy to use R package that can decompose an individual tumor genome into a given set of Alexandrov-type or Shiraishi-type signatures, thus quantifying the contribution of the corresponding mutational processes to the somatic mutations identified in the tumor. Until now, such tools were available only for Alexandrov signatures. We demonstrate the correctness and usefulness of our approach with three test cases, using somatic mutations from 21 breast cancer genomes, from 435 tumor genomes of ten different tumor entities, and from simulated tumor genomes, respectively.

Conclusions The decompTumor2Sig package is freely available and has been accepted for inclusion in Bioconductor.