FFPE Impact

Description

This R script is designed to analyze the impact of formalin-fixed paraffin-embedded (FFPE) artefacts on mutation signatures within genomic data. It leverages the capabilities of the signature.tools.lib library to fit substitution (SBS) and indel (ID) signatures to mutation catalogues derived from FFPE samples. The script calculates the FFPE impact on mutation signatures and adjusts the mutation catalogue to mitigate artefact effects.

Prerequisites

To use this script, you will need to have R and the signature.tools.lib library installed. The signature.tools.lib library is crucial as it provides the necessary functions for fitting mutation signatures and other related analyses. If you do not have signature.tools.lib installed, you can find installation instructions here:

https://github.com/Nik-Zainal-Group/signature.tools.lib

Input Requirements

Before running the script, you must define the following parameters:

• SNV_path: The file path to the single nucleotide variant (SNV) catalogue.
• ID_path: The file path to the indel (ID) catalogue.
• organ: The organ type of the sample(s). This must be one of the organs recognized in the FitMS function from signature.tools.lib.

Make sure that the SNV_path and ID_path point to valid files containing your mutation data in a format readable by read.table(). The organ type should match one of the supported types in signature.tools.lib to ensure accurate signature fitting - it is now possible to specify organ="Other" in FitMS.

Usage

Load the script into your R environment and call the FFPE_impact function with the necessary parameters:

source("FFPE_impact.R")
result <- FFPE_impact(SNV_path = "your/SNV/file/path.tsv",
                      ID_path = "your/ID/file/path.tsv",
                      organ = "yourOrganType")

Output

The script returns a list containing the following components:

• SBS_exposures: Exposure estimates for SBS signatures.
• ID_exposures: Exposure estimates for ID signatures.
• FFPE_impact: Calculated impact of FFPE artefacts on mutation signatures.
• cleaned_catalogues: The mutation catalogue adjusted for FFPE artefact effects.
• newMHcount: Proportions of microhomology-associated deletions post artefact adjustment.

These outputs facilitate further analysis of the FFPE artefact impact and the evaluation of mutation signatures in your genomic data.

Authors

Shadi Basyuni

Acknowledgments

This script is dependent on the signature.tools.lib library for performing mutation signature analysis. We acknowledge the authors and contributors of signature.tools.lib for their valuable work.