Recent years saw the development of methods to detect signals of positive selection in the pattern of somatic mutations in genes across cohorts of tumors, and the discovery of hundreds of driver genes. The next major challenge in tumor genomics is the identification of non-coding regions which may also drive tumorigenesis. We present OncodriveFML, a method that estimates the accumulated functional impact bias of somatic mutations in any genomic region of interest based on a local simulation of the mutational process affecting it. It may be applied to all genomic elements to detect likely drivers amongst them. OncodriveFML can discover signals of positive selection when only a small fraction of the genome, like a panel of genes, has been sequenced.
OncodriveFML is made available to the general public subject to certain conditions described in its LICENSE. For the avoidance of doubt, you may use the software and any data accessed through UPF software for academic, non-commercial and personal use only, and you may not copy, distribute, transmit, duplicate, reduce or alter in any way for commercial purposes, or for the purpose of redistribution, without a license from the Universitat Pompeu Fabra (UPF). Requests for information regarding a license for commercial use or redistribution of OncodriveFML may be sent via e-mail to firstname.lastname@example.org.
OncodriveFML depends on Python 3.5 and some external libraries. The easiest way to install all this software stack is using the well known Anaconda Python distribution:
$ conda install -c bbglab oncodrivefml
OncodriveFML can also be installed using pip:
pip install oncodrivefml
Finally, you can get the latest code from the repository and install with pip:
$ git clone email@example.com:bbglab/oncodrivefml.git $ cd oncodrivefml $ pip install .
OncodriveFML has a set up dependency with Cython, which is required to compile the *.pyx files.
The first time that you run OncodriveFML it will download the genome reference from our servers. By default the downloaded datasets go to ~/.bgdata if you want to move these datasets to another folder you have to define the system environment variable BGDATA_LOCAL with an export command.
The following command will show you the help:
$ oncodrivefml --help
Run the example
Download and extract the example files (if you cloned the repository skip this step):
$ wget https://bitbucket.org/bbglab/oncodrivefml/downloads/oncodrivefml-examples_v2.0.tar.gz $ tar xvzf oncodrivefml-examples_v2.0.tar.gz
To run this example OncodriveFML needs all the precomputed CADD scores, that is a 17Gb file. It will be automatically downloaded the first time you run OncodriveFML, but if you want to speed up the process it is better to first download it using our data package management tool (BgData) that is also installed when you install OncodriveFML.
Run this command to download the CADD scores file to the default bgdata folder ~/.bgdata:
$ bg-data genomicscores caddpack 1.0
CADD scores are originally from http://cadd.gs.washington.edu/ and are freely available for all non-commercial applications. If you are planning on using them in a commercial application, please contact them at http://cadd.gs.washington.edu/contact.
Additonally, if you want to speed up the download of the genome reference that is also needed, run this command:
$ bg-data datasets genomereference hg19
To run the example, we have included a bash script (run.sh) than will execute OncodriveFML. The script should be executed in the folder where the files have been extracted:
The results will be saved in a folder named cds.