Genome-editing systems are increasingly used to advance cell therapies, but edited cellular systems need to be thoroughly characterized to fully understand the exact nature of induced mutations. Both on and off-target effects must be measured through high-sensitivity detection methods. Single-cell resolution supports genome-editing system optimization by enabling the detection of low-frequency events – down to 0.1% of cells. Furthermore, single-cell data resolves the complexities of mutation zygosity and co-occurrence in a genome-editing experiment targeting multiple loci. The Tapestri Platform offers a turnkey solution to the complex challenge of characterizing genome-edited systems.