Question: Displaying somatic mutational signatures
gravatar for kezcleal
5.0 years ago by
United Kingdom
kezcleal160 wrote:

Sorry if this is a very basic question. Ive been following the methodology of Alexandrov et al.,2013 (see 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


snp genome • 2.6k views
ADD COMMENTlink modified 5.0 years ago by trausch1.6k • written 5.0 years ago by kezcleal160

I am currently also confused by this statement. The way I currently interpret this is the following:

Each published signatures seems to sum up to 1 over the 96 dimensions. This, I assume, refers to the "relative proportion of the mutations generated by each signature". This leaves the normalization by the trinucleotide frequency: to ensure the normalization to 1 per signature still holds, I think this was done before the above.

I.e. given an un-normalized mutational signature S and the trinucleotide frequency T, the published signature would be: (S/T) / sum(S/T).

ADD REPLYlink written 2.9 years ago by Alex0
gravatar for trausch
5.0 years ago by
trausch1.6k wrote:

The Bioconductor package SomaticSignatures is very convenient for this:

ADD COMMENTlink modified 12 months ago by _r_am32k • written 5.0 years ago by trausch1.6k

Thanks, I will give this a try

ADD REPLYlink written 5.0 years ago by kezcleal160

Does SomaticSignature package tells whether the identified signature is similar to signature-1 or signature-2 ........signature-30 from

I did not find in the manual where it said how similar it is to cosmic signatures.

ADD REPLYlink written 3.9 years ago by Chirag Nepal2.3k

In particular, should be helpful with regards to normalizing between e.g. exome and whole genome.

ADD REPLYlink written 2.9 years ago by Alex0
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