Mutational Signatures (v3.3 - June 2022)

Doublet base substitutions (DBS) are generated after the concurrent modification of two consecutive nucleotide bases. There are 78 strand-agnostic DBS mutation types, enumerated here.

More specifically, there are 16 possible source doublet bases (4 x 4). Of these, AT, TA, CG, and GC are their own reverse complement. The remaining 12 can be represented as 6 possible strand-agnostic doublets. Thus, there are 4+6=10 source doublet bases. Because they are their own reverse complements, AT, TA, CG, and GC can each be substituted by only 6 doublets. For the remaining doublets, there are 9 possible DBS mutation types (3 x 3). Therefore, in total there are 4 x 6 + 6 x 9 = 78 strand -agnostic DBS mutation types.

Click on any signature below to learn more about its details.

Signature extraction methods

With a few exceptions, the current set of reference signatures were extracted using SigProfiler (as described in Alexandrov, L.B. et al., 2020) from the 2,780 whole-genome variant calls produced by the ICGC/TCGA Pan Cancer Analysis of Whole Genomes (PCAWG) Network. The stability and reproducibility of the signatures were assessed on somatic mutations from an additional 1,865 whole genomes and 19,184 exomes. All input data and references for original sources are available from synapse.org ID syn11801889.

COSMIC mutational signatures are available in numerical form in our data downloads page.