Next-generation DNA sequencing of the exome has detected hundreds of thousands of small somatic variants (SSV) in cancer. However, distinguishing genes containing driving mutations rather than simply passenger SSVs from a cohort sequenced cancer samples requires sophisticated computational approaches. 20/20+ integrates many features indicative of positive selection to predict oncogenes and tumor suppressor genes from small somatic variants. The features capture mutational clustering, conservation, mutation in silico pathogenicity scores, mutation consequence types, protein interaction network connectivity, and other covariates (e.g. replication timing). Contrary to methods based on mutation rate, 20/20+ uses ratiometric features of mutations by normalizing for the total number of mutations in a gene. This decouples the genes from gene-level differences in background mutation rate. 20/20+ uses monte carlo simulations to evaluate the significance of random forest scores based on an estimated p-value from an empirical null distribution.
Please see the documentation on readthedocs.
You can download releases on github.
20/20+ is designed to run on linux operating systems.
We recommend that you install the dependencies for 20/20+ through conda. Once conda is installed, setting up the environment is done as follows:
$ conda env create -f environment_python.yml # install dependencies for python
$ source activate 2020plus # activate the 20/20+ conda environment
$ conda install r r-randomForest rpy2 # install the R related dependenciesEvery time you wish to run 20/20+, you will then need to activate the "2020plus" conda environment.
$ source activate 2020plusThe 20/20+ conda environment can also be deactivated.
$ source deactivate 2020plus