Package demo: Enhanced Deconvolution and Prediction of Mutational Signatures

Enhanced Deconvolution and Prediction of Mutational Signatures

Aaron Chevalier,Joshua D Campbell Boston University

Abstract

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 select different schemas for counting mutation types and easily combine count tables from different schemas. Multiple distinct methods are available to deconvolute signatures and exposures or to predict exposure in individual samples for a pre-existing set of signatures. Additional exploratory features include the ability to compare signatures to the COSMIC database, embed tumors in two dimensions with UMAP, 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. Overall, musicatk will enable users to gain novel insights into the patterns of mutational signature observed in cancer cohorts.

Keywords: The Mutational Signature Comprehensive Analysis Toolkit (musicatk) for the discovery,prediction,and exploration of mutational signatures