Sorry if this is a very basic question. Ive been following the methodology of Alexandrov et al.,2013 (see http://cancer.sanger.ac.uk/cosmic/signatures) to find the mutational signature of a cancer sample and have become confused about how mutational signatures are supposed to be displayed on a graph, relating to the normalising of mutation counts. From the cosmic website:
"Mutational signatures are displayed and reported based on the observed trinucleotide frequency of the human genome, i.e., representing the relative proportions of mutations generated by each signature based on the actual trinucleotide frequencies of the reference human genome version GRCh37."
Do I need to count the frequency of trinucleotide repeats in the human genome and then somehow normalise to this? I am a bit confused about what this sentence means.
Hypothetical example for a C>A substitution type and ACA context;
If the mutation frequency in my sample is 1% and the trinucleotide frequency of ACA in the human genome is 3.5%, what do I do next? Many thanks