Mutational Signatures (v3.5 - November 2025)

The reason there are 78 strand-agnostic DBS mutation types is as follows. First, there are 4 x 4 = 16 possible source doublet bases. Of these, AT, TA, CG, and GC are their own reverse complement. We can represent the remaining 12 as 6 possible strand-agnostic doublets (e.g. AC represents both AC and its reverse complement, GT). 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 example, AT can be substituted by 3 doublets starting with C: CA, CC, CG. But AT can be substituted by only 2 doublets starting with G: GA and GC. This is because the mutation from AT>GG is already represented by its reverse complement, AT>CC. Similarly AT can be substituted by only 1 doublet starting with T: TA. This is because AT>TC is represented by its reverse complement, AT>GA, and AT>TG is represented by AT>CA. For the remaining doublets, which are not their own reverse-complements, there are 3 x 3 = 9 possible DBS mutation types. Thus, in total there are 4 x 6 + 6 x 9 = 78 strand-agnostic DBS mutation types (see enumeration in the accompanying Excel document).