Fig. 1

Example of a clonal tree. Four clones are drawn by big circles. A smaller black circle indicates the founder cell of the subsequent clone. The left-most dark circle is the MRCA cell of the tumour, which undergoes clonal expansion to create the first clone, which is defined by clonal mutations of a cancer cell fraction (CCF\(=1\)). Subsequent clones are defined by subclonal mutations of CCF\(<1\). The mutations that define each clone might be of diverse origin: here we depict two active mutational processes (grey and red arrows) creating mutations at two distinct rates. Whilst the mutational process represented by grey arrows is more active at early stages of tumour development, in creating the mutations that define the first clone, the mutational process presented by red arrows has a constant mutation rate. We can quantify the number of mutations created by each mutational processes by extracting signature exposures, which are indicated for each of the clones. These signature exposures can be finally aggregated to clonal exposures (those of clone 1) and subclonal exposures (in this case, those of clone 2 and clone 4). Clone 3 might be interpreted as a clone which is not represented in the sample that has been taken, and for which we therefore not have mutation information