The article introduces TIDE (Tracking of Indels by DEmposition), a method for assessing the efficacy and mutation spectrum of genome editing methods. TIDE is designed to be simple, rapid, and cost-effective, requiring only two PCR reactions and two capillary sequencing runs. The sequence traces are analyzed using a specialized decomposition algorithm that identifies and quantifies the major induced mutations in the target site. This method provides detailed information about the nature and diversity of mutations, which is crucial for establishing clonal cell lines with specific editing outcomes. The authors demonstrate the effectiveness of TIDE through in vitro simulations and in vivo experiments, showing high sensitivity and robustness. TIDE offers a valuable tool for optimizing genome editing strategies and studying DSB repair mechanisms.The article introduces TIDE (Tracking of Indels by DEmposition), a method for assessing the efficacy and mutation spectrum of genome editing methods. TIDE is designed to be simple, rapid, and cost-effective, requiring only two PCR reactions and two capillary sequencing runs. The sequence traces are analyzed using a specialized decomposition algorithm that identifies and quantifies the major induced mutations in the target site. This method provides detailed information about the nature and diversity of mutations, which is crucial for establishing clonal cell lines with specific editing outcomes. The authors demonstrate the effectiveness of TIDE through in vitro simulations and in vivo experiments, showing high sensitivity and robustness. TIDE offers a valuable tool for optimizing genome editing strategies and studying DSB repair mechanisms.