SelectSim is an R package that infers evolutionary dependencies i.e co-mutations and mutual exclusivities — between functional alterations across cancer genomes. It estimates the expected co-mutation frequency for each gene pair from individual mutation frequencies and per-sample tumor mutation burden (TMB), then evaluates significance against a simulation based null model.
The method accounts for heterogeneous tumor types, tissue specificities, and distinct mutational processes through a covariate-aware weighting scheme. Significance is assessed as a weighted effect size with frequency-stratified FDR control generated via simulation.
This package accompanies the manuscript:
Iyer A, Petrovic M, Sesia D, Nanni L, Mina M, Ciriello G (2026). Evolving patterns of co-mutations from tumor initiation to metastatic progression. Nature Genetics. DOI: 10.1038/s41588-026-02661-4
You can install the development version of SelectSim from GitHub with:
# install.packages("pak")pak::pak("CSOgroup/SelectSim")For more details on installation refer to INSTALLATION.
library(SelectSim)
library(dplyr)
# Load the bundled TCGA LUAD example data
data(luad_run_data, package="SelectSim")
# Run SelectSim (1 000 permutations, single core)result<- selectX(
M=luad_run_data$M,
sample.class=luad_run_data$sample.class,
alteration.class=luad_run_data$alteration.class,
n.cores=1,
min.freq=10,
n.permut=1000,
lambda=0.3,
tau=1,
maxFDR=0.25
)
# Significant evolutionary dependencies at FDR ≤ 0.25result$result|> filter(nFDR2<=0.25) |> head()For a full walkthrough see the Introduction vignette.
Full documentation and vignettes are available at https://csogroup.github.io/SelectSim/.
If you use SelectSim in your research, please cite:
Iyer A, Petrovic M, Sesia D, Nanni L, Mina M, Ciriello G (2026). Evolving patterns of co-mutations from tumor initiation to metastatic progression. Nature Genetics. DOI: 10.1038/s41588-026-02661-4
You can also run citation("SelectSim") inside R for a formatted
reference.
- For bugs or feature requests, please use the issue tracker.
- For other questions, contact Prof. Giovanni Ciriello (giovanni.ciriello@unil.ch) or Arvind Iyer (ayalurarvind@gmail.com).