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SelectSim

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

Installation

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.

Quick start

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 ≤ 0.25
result$result |> filter(nFDR2 <= 0.25) |> head()

For a full walkthrough see the Introduction vignette.

Documentation

Full documentation and vignettes are available at https://csogroup.github.io/SelectSim/.

Citation

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.

Contact

• 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).

These binaries (installable software) and packages are in development.
They may not be fully stable and should be used with caution. We make no claims about them.
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