Methods of assessing nuclease cleavage

A method for analyzing cleavage and/or repair events for a site specific nuclease, the method comprising:

• (a) contacting a cell or tissue with the site specific nuclease, wherein contacting the cell or tissue with the site specific nuclease results in cleavage and/or repair of genomic DNA in the cell or tissue;
• (b) obtaining a genomic DNA sample from the cell or tissue that has been contacted with the site specific nuclease;
• (c) contacting the genomic DNA sample with a transposase and a transposon comprising a first detection sequence at the 5′ end of the transposon, under conditions whereby the transposon is inserted into the genomic DNA sample and the genomic DNA sample is fragmented into a plurality of tagmented double-stranded nucleic acid fragments comprising the transposon attached to the 5′ end of the nucleic acid fragments;
• (d) amplifying the tagmented nucleic acid fragments using
• (i) a first fixed primer comprising a nucleotide sequence complementary to a predetermined location in the genomic DNA and comprising a second detection sequence at its 5′ end, and
• (ii) a second selective primer comprising a nucleotide sequence complementary to at least a portion of the first detection sequence,
• to form amplified nucleic acid fragments comprising the first detection sequence, the transposon attached to the 5′ end of the nucleic acid fragments, and the second detection sequence;
• (e) sequencing the amplified nucleic acid fragments to generate sequencing data;
• and
• (f) analyzing the sequencing data for the cleavage and/or repair events of the site specific nuclease.