Behind the scenes

This section will point out some parts which might be interesting if you are running OncodriveFML yourself.

Command line interface

The command line interface of OncodriveFML overwrites some of the parameters in the configuration file.

Warning

This overwrite is performed regardless the parameter is set or not in the configuration file.

The following table shows the modifications introduced in the indels configuration parameters by the --type flag:

Effects of –type

Value	Effect in configurtion of indels
coding	method = 'stop'
noncoding	method = 'max'

The flag --no-indels also affects the indels configuration parameters. Particularly, it has effect on the include option. The use of this flag discards the analysis of indels by setting include = False, while not using it includes indels (include = True).

The table below shows the effects of the --sequencing flag in the signature configuration:

Effects of –sequencing

Value	Effect in signature
wgs	normalize_by_sites = 'whole_genome'
wes	normalize_by_sites = 'whole_exome'
targeted	normalize_by_sites = None

Finally, the use of the --debug flag sets the level of the console handler in the logging section to 'DEBUG'.

Pickle files

OncodriveFML can create and use intermediate files to speed up computations that use the same files.

The regions file is loaded using the BgParsers library, so the cache of that file is out of the scope of OncodriveFML. In short, the file will be cached the first time you use it and rebuild if you change its name or content.

There are 2 other items for which OncodriveFML can create or use a cache-like files to speed up future executions. Those files are saved in (or loaded from) the same folder as the mutations file. However, the systems is not as sophisticated as the BgParsers and may lead to few issues. To generate these cache-like files you need to run OncodriveFML with the --generate-pickle option (you can list all the options using the help).

Warning

Using this option can speed up computations as some steps can be replaced by a single file read. However, changes in the input files are not noticed by these pickle files unless you rename them. Thus we recommend its use only to advanced users that understand the process.

Mutations

One of the pickle files that can be created contains a dictionary with the mutations mapped to the genomic elements being analysed and some other useful metadata (such as the number of indels or SNP mutations). This file, named <mutations file>+__mapping__+<elements file>, is helpful to skip the steps of loading and mapping mutations. If this file is in the same location as the mutations file, OncodriveFML loads it as long as it does not receive any file with blacklisted samples.

Signature

The other pickle file created is the signature pickle. It is only created for signature methods: full and complement Its name is: <mutations file>+_signature_+<method>+_+<classifier>. See signature configuration for more details (methods, classifiers, etc.) about the signature.

If this file is located in the same directory as the mutations file, OncodriveFML loads it as long as it does not receive any file with blacklisted samples and the only_mapped_mutations option is not used (see signature configuration).

BgData

OncodriveFML uses external data retrieved using the BgData package. You can download and check this data yourself. If you want to use different data, you can download the source code and modify the code to use your own data.

Reference genome

As March 2017 BgData includes three reference genomes: HG18, HG19 and HG38.

bgdata datasets genomereference hg19

If you want to use a different genome, you need to modify the code in the oncodrivefml.signature module.

Signature correction

BgData includes the counts of the triplets in whole exome and whole genome.

bgdata datasets exomesignature hg19

bgdata datasets genomesignature hg19

Those counts are used to compute the trinucleotides frequencies and to perform signature correction (find more details in the signature section and in the signature configuration).

Gene stops

OncodriveFML also uses a tabix file that contains the positions and the alterations of the gene stops.

bgdata datasets genestops hg19