. Author manuscript; available in PMC: 2016 Nov 1.

Published in final edited form as: Nat Protoc. 2016 Mar 31;11(5):853–871. doi: 10.1038/nprot.2016.043

Table 1.

Various methods to locate DSBs

Method^*	In vivo/ In situ/ In vitro	Assay Type	Comments
BLESS³⁷	In situ	Maps un-joined broken ends with sequence-specific adapter	Unbiased; high background; narrow time-window (only maps un-joined ends)
ChIP-seq^18,34,35	In vivo	Pulls down proteins specifically binding to broken ends or processed ends	Highly depends on the quality of antibody; narrow time-window (only maps un-joined ends); low resolution
Digenome-seq⁴⁴	In vitro	Cleavage of genomic DNA followed by standard whole genome sequencing	Requires in vivo cleavage confirmation; high skill requirement for bioinformatic analysis
DSB-seq³⁶	In vitro	Maps un-joined broken ends with biotinylated adapter	Unbiased; high background; narrow time-window (only maps un-joined ends)
GUIDE-seq²⁷	In vivo	Randomly incorporates sequence-specific dsDNA fragment into DSB sites	Unbiased; currently limited use for blunt-ended DSBs
HTGTS¹¹	In vivo	Maps translocations with induced DSBs	Relatively higher cost and lower sensitivity compared to LAM-HTGTS
IDLV^28,45	In vivo	Randomly incorporates integrase-deficient viral DNA into DSB sites	Low detection frequency; requires high skill; high cost
LAM-HTGTS^6,8-10	In vivo	Maps translocations with induced or highly recurrent DSBs	Higher sensitivity on the break-site chromosome; not applicable to limited material
TC-seq³³	In vivo	Maps translocations with induced DSBs	Does not resolve junction structures; relatively higher cost and lower sensitivity compared to LAM-HTGTS
Whole genome sequencing (WGS)⁴⁶	In vivo	Deep genome sequencing	Covers all types of mutations; expensive; high skill requirement for bioinformatic analysis

Due to space limitations, only typical methods and references were cited here.