Mitochondrial ribosomal RNA is the target of functionally dominant hotspot mutations in cancer

Clone the directory:

git clone https://github.com/reznik-lab/rrna-hotspots.git

All packages can be installed from

./analysis/prerequisites.R

Whole-Genome-Sequencing Analysis (GEL)

1. mtDNA mutation calling across the GEL cohort was conducted within the genomics england research environment.

2. To calculate hotspot mutations, a master maf file is passed as input.

./analysis/run_hotspots_snv.R

3. To produce figures 1 and 2, the code is available here:

./analysis/generate_all_figures_01_05.Rmd

Single-Cell Multiome Analysis

1. To call mtDNA mutations, mgatk v.7.0 was used on the 10x output to produce a parseable Seurat object. We have uploaded the count matrices and the resulting Rds objects from running mgatk to Zenodo:

10.5281/zenodo.14207223
git clone https://github.com/caleblareau/mgatk

Then specific variants were parsed using:

./analysis/get_mutations_atac_data.R

The remaining analysis to produce figure 3 is available at

./analysis/generate_fig3scRNAseqfigs.Rmd

Proteomics and Metabolomics Analysis

Code to generate figures is available at:

./analysis/generate_functional_figs.Rmd