Fig. 2

Experimental designs. a An example of a genetic manipulation experiment to link specific gene edit to mutational patterns. Note that upon parental clone derivation, mutations might accumulate over several cellular generations to reveal mutational patterns. The number of doublings (n) required for mutation accumulation is gene- and/or model system-specific. b An example of a genotoxin treatment experiment to link specific genotoxin exposure to mutational patterns. Here, mutations accumulate as a result of treatment; treated cells (and controls) are effectively the parental clones. Repeated cycles of treatment following recovery may help amplify the signals by increasing the mutation burden. It is imperative to sequence grandparental clones as the normal genetic reference. The background mutagenesis can be determined through the control subclones