Caveats

MNP mutations contribute to the signatures as a set of independent SNPs mutations. This means that the calculation of the signatures is made with a higher number of mutations compared to the observed substitutions being analysed because OncodriveFML simulates a MNP mutation as a single SNP mutation.

If the scores files lacks scores for some positions or certain alterations, OncodriveFML ignores them.

If, for any reason, your signatures lack certain triplets (probability equal to 0) that are the only ones present in certain region, OncodriveFML will not compute a P-value for that region.

OncodriveFML statistical power is limited by the number of simulations performed in each regions. You can increase the number of simulations, but be aware that the time cost is exponential.

Indels do not contribute to the signatures. You can simulate indels as substitutions and perform the simulations taking the signatures into account, but be aware that the signatures are not calculated considering indels.

On the other hand, if you choose to not use the signatures with the indels, their probability is the inverse of the number of distinct trinucleotides for all the regions multiplied by three (there are 3 possible changes). Typically the value should be 1/192, and that is the default value OncodriveFML uses. If OncodriveFML corrects the signatures, it obtains the number of distinct triplets from the correction.

Depending on the values of sampling_min_obs and sampling_chunk in the configuration file the number of simulations performed for a particular genomic element can differ.