The Mutational Signature Comprehensive Analysis Toolkit (musicatk) for the Discovery, Prediction, and Exploration of Mutational Signatures

Author(s): Natasha Gurevich,Aaron Chevalier,Joshua Campbell

Affiliation(s): Boston University



Mutational signatures are patterns of somatic alterations in the genome caused by carcinogenic exposures or aberrant cellular processes. To provide a comprehensive workflow for preprocessing, analysis, and visualization of mutational signatures, we created the Mutational Signature Comprehensive Analysis Toolkit (musicatk) package. Musicatk enables users to count and combine multiple mutation types, including SBS, DBS, and indels. Multiple distinct methods are available to deconvolute signatures and exposures or to predict exposures in individual samples given a pre-existing set of signatures. Additional exploratory features include the ability to compare signatures to the Catalogue of Somatic Mutations In Cancer (COSMIC) database, embed tumors in two dimensions with uniform manifold approximation and projection, cluster tumors into subgroups based on exposure frequencies, identify differentially active exposures between tumor subgroups, and plot exposure distributions across user-defined annotations such as tumor type. Accessibility and usability is improved with the Shiny graphical user interface (GUI). Variants may be imported by uploading MAF or VCF files containing variant data, or by importing from open access TCGA tumor datasets. Existing musica and result objects may also be imported for further analysis. Preprocessing utilities, discovery and prediction tools, and functions for downstream analysis and visualization are all implemented in a user-friendly manner with the GUI. Overall, musicatk will enable users to gain novel insights into the patterns of mutational signatures observed in cancer cohorts.