SelectSim/README.Rmd at main · CSOgroup/SelectSim · GitHub

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---
output: github_document
---

<!-- README.md is generated from README.Rmd. Please edit that file -->

```{r, include = FALSE}
knitr::opts_chunk$set(
  collapse = TRUE,
  comment = "#>",
  fig.path = "man/figures/README-",
  out.width = "100%"
)
```

# SelectSim <a href="https://csogroup.github.io/SelectSim/"><img src="man/figures/logo.png" align="right" height="138" alt="SelectSim website" /></a>

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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.

![SelectSim Method](man/figures/SelectSim_method.png)

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](https://doi.org/10.1038/s41588-026-02661-4)

## Installation

You can install the development version of SelectSim from [GitHub](https://github.com/CSOgroup/SelectSim) with:

``` r
# install.packages("pak")
pak::pak("CSOgroup/SelectSim")
```

For more details on installation refer to [INSTALLATION](INSTALLATION.md).

## Quick start

```{r quickstart, eval = FALSE}
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](https://csogroup.github.io/SelectSim/articles/introduction.html).

## 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](https://doi.org/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](https://github.com/CSOgroup/SelectSim/issues).
- For other questions, contact Prof. Giovanni Ciriello (giovanni.ciriello@unil.ch) or Arvind Iyer (ayalurarvind@gmail.com).