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

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 to easily combine count tables from different schemas. 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. Overall, musicatk will enable users to gain novel insights into the patterns of mutational signatures observed in cancer cohorts. Significance: The musicatk package empowers researchers to characterize mutational signatures and tumor heterogeneity with a comprehensive set of preprocessing utilities, discovery and prediction tools, and multiple functions for downstream analysis and visualization.

DETexT: An SNV detection enhancement for low read depth by integrating mutational signatures into TextCNN

“…Mutational processes from different etiologies are active during cancer development and can be identified by MS due to their unique mutational pattern and specific activity on the genome. The results reveal the diversity of mutational processes during the development of cancer and have potential implications for understanding cancer etiology (Tianyuan Liu et al, 2022 ), prevention (Aaron Chevalier et al, 2021 ), and therapy ( Drews et al, 2022 ).…”

HNRNPC regulates RhoA to induce DNA damage repair and cancer‐associated fibroblast activation causing radiation resistance in pancreatic cancer

“…The RhoA/ROCK pathway has been implicated in dynamic crosstalk regulation between cancer cells and their microenvironment, which may be used to inhibit cancer metastatic processes. 42,43 Rho inhibition has been shown to decrease tumour cell survival after radiation treatment, while ROCK inhibitors, in particular, may enhance chemo-and radiotherapy efficacy. 44 Rho/ROCK inhibitors may also act as pro-vascular agents to improve tumour blood flow and increase cell exposure to chemotherapy or even sensitize cells to the radiation effects.…”

“…The RhoA/ROCK pathway has been implicated in dynamic crosstalk regulation between cancer cells and their microenvironment, which may be used to inhibit cancer metastatic processes 42,43 . Rho inhibition has been shown to decrease tumour cell survival after radiation treatment, while ROCK inhibitors, in particular, may enhance chemo‐ and radiotherapy efficacy 44 .…”

Cutting-Edge AI Technologies Meet Precision Medicine to Improve Cancer Care

“…These mutational signatures provide additional information on the etiology and progression of individual cancers, as well as new biomarkers for cancer treatment [ 41 ]. New technologies and machine learning algorithms have increased the feasibility of identifying mutational signatures [ 42 , 43 , 44 , 45 , 46 ] and facilitated the integration of signature analysis into clinical decision-making. The Catalogue of Somatic Mutations in Cancer (COSMIC) Signatures [ 42 ], DeaminationSigs [ 44 ], and SparseSignatures [ 45 ] are standard tools for cancer etiology and quality control based on non-negative matrix factorization (NMF) algorithms ( Table 2 ).…”

“…For DeconstructSigs, a multiple linear regression model was used [ 43 ]. Chevalier et al established an analysis and visualization tool to characterize and enhance the discovery of mutational signatures [ 46 ].…”