# SigRescueR: a pan-system framework for noise correction and mutational signature identification across sequencing platforms

## TL;DR

SigRescueR is a new computational tool that improves accuracy in identifying cancer-related mutational signatures by reducing noise from sequencing data.

## Contribution

Introduces SigRescueR, a Bayesian framework for noise correction and mutational signature identification across sequencing platforms.

## Key findings

- SigRescueR reliably identifies mutational signatures from environmental mutagens and chemotherapeutic agents.
- The framework operates across diverse mutation classes and integrates strand bias and duplex sequencing data.
- It enables precise mapping of mutagenic processes and identification of genomic biomarkers for exposures.

## Abstract

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.

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.

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.

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.

SigRescueR is implemented in R and provided as open-source software on GitHub at https://github.com/ZhivaguiLab/SigRescueR/

Graphical Abstract