Document Type

Article

Publication Date

3-6-2026

Publication Title

Briefings in Bioinformatics

Volume

27

Issue

2

First page number:

1

Last page number:

14

Abstract

Introduction: Mutational signatures serve as molecular fingerprints of the biological processes and exposures that shape cancer genomes. However, accurate signal recovery remains challenging due to pervasive background variants, sequencing artifacts, technical noise, and platform-specific biases that obscure true mutagenic patterns, hampering biomarker discovery, and mechanistic interpretation. Methods: Here we introduce SigRescueR, a rigorous, pan-system, computational framework based on Bayesian inference designed for noise correction and mutational signature identification. SigRescueR applies statistically robust baseline correction to effectively disentangle true mutational signals from confounding noise and artifacts. Results: When applied to extensive datasets spanning experimental models and human cancers, SigRescueR reliably identified canonical mutational signatures associated with environmental mutagens such as colibactin, benzo[a]pyrene, and UV radiation, and chemotherapeutic agents, namely 5-fluorouracil and cisplatin. SigRescueR effectively operated across diverse mutation classes, including single base substitutions, insertions and deletions, and doublet base substitutions, while also integrating strand bias and duplex sequencing data for toxicology applications. Conclusion: SigRescueR offers a unified, high-precision platform that seamlessly integrates cancer genomics, molecular toxicology, and mechanistic studies. It enables precise mapping of mutagenic processes and identification of robust genomic biomarkers of environmental and therapeutic exposures, providing a transformative framework for translational cancer research.

Keywords

cancer; genomics; mutational signature; model systems; benchmark

Disciplines

Cancer Biology | Cell Biology

File Format

PDF

File Size

2100 KB

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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