In Nature Biotechnology this week, a team from Boston Children's Hospital describes a new genome-wide method for detecting DNA double-strand breaks generated by engineered nucleases. By combining high-throughput, genome-wide translocation sequencing with different CRISPR/Cas9 and TALEN gene-editing nucleases, the researchers identified off-target hotspot numbers for the given nucleases and extended the number of known off-targets for certain previously characterized nucleases.