The somatic mutations in the pathways that drive cancer development tend to be mutually exclusive across tumors, providing a signal for distinguishing driver mutations from a larger number of random passenger mutations. This mutual exclusivity signal can be confounded by high and highly variable mutation rates across a cohort of samples. Current statistical tests for exclusivity that incorporate both per-gene and per-sample mutational frequencies are computationally expensive and have limited precision.
WExT is a weighted exact test for assessing the significance of mutual exclusivity in an arbitrary number of mutational events. It conditions on the number of samples with a mutation as well as per-event, per-sample mutation probabilities. We provide a recursive formula to compute P-values for the weighted test exactly as well as a highly accurate and efficient saddle-point approximation of the test.
The Weighted Exclusivity Test (WExT) was developed by the Raphael research group at Brown University and originally implemented as a command line tool running in Python. This is an adaptation for R with specific intention to be compatible with the ‘tidyverse’.
This package is still in development and not ready for use.
You can install the released version of wext from CRAN with:
install.packages("wext")or from GitHub using ‘devtools’:
devtools::install_github("jhrcook/wext")