Extended Data Fig. 1: Prime editing has a greater capacity to model recurrent cancer-associated mutations than base editing.

a Quantification of mutations that are detected in multiple patients in cancer-associated genes, depicted for each mutant variant type (Single nucleotide variants = SNV, deletions = DEL, insertions = INS, di-nucleotide variants = DNV, oligo-nucleotide variants = ONV). The y-axis in all plots indicates the total number of unique mutations per variant type. b Quantification of recurrent mutations potentially amenable to modeling by a base editor with an NGG PAM (top) or a prime editor with an NGG PAM and a 30 base pair RT template (bottom). The columns show results considering mutations that occur in ≥5 patients (left) or ≥10 patients (right). ‘CBE/ABE high’ indicates that the SNV falls in the high efficiency editing window (position +4 to +8 in the protospacer), while ‘CBE/ABE low’ indicates the SNV falls within the protospacer but outside the high efficiency window. The data include SNVs (blue outer circle; 78.8% of mutations) and other mutation types (gray outer circle; 20.2% of mutations). All calculations assume a base or prime editor that recognizes only NGG PAMs. c Total percentage of recurrent mutations amenable to modeling by a base editor with an NGG PAM, quantified at multiple thresholds of mutation frequency, from mutations that occur ≥1 patient to those that occur ≥10 patients. d Total percentage of recurrent mutations amenable to modeling by a prime editor with an NGG PAM and a 30 base pair RT template at multiple thresholds of mutation frequency, from mutations that occur ≥1 patient to those that occur ≥10 patients. e Capabilities of prime versus base editing to model orthologous mutations in mice at multiple thresholds of mutation frequency, from ≥1 to ≥10 patients with each mutation. Prime editing can model approximately double the number of orthologous mutations in mice at all thresholds of mutation frequency. Base editing (BE) shown in red. Prime editing (PE) shown in blue. f Quantification of the ability of base editing (left) and prime editing (right) to model orthologous mutations in mice for mutations that occur in ≥5 or ≥ 10 patients.