TABLE 1.

Main technologies of 3D genomics.

Technologies	Characteristics	Advantages	Limitation	Reference
3C	The interaction mode is one versus one	Precisely detects the interaction between two target regions	Low throughput; low resolution	Dekker et al. (2002)
4C	Reverse PCR; the interaction mode is one versus all	Detects the interactions between one target region with genome	Interaction data are prone to bias	Simonis et al. (2006)
5C	Multiple Primer design; the interaction mode is many versus many	Detects interactions among multiple regions	Low coverage and difficult-to-assess PCR redundancy	Dostie et al. (2006)
Hi-C	Interaction mode is all versus all	High-throughput detection of genome-wide interactions	High cost of sequencing; difficult to analyze because of the large amount of data	Lieberman-Aiden et al. (2009)
Capture-C	Target domain capture	Provide an unbiased, high-resolution map of cis interactions for hundreds of genes in a single experiment.	Sampling is limited to a defined domain of chromatin	Hughes et al. (2014)
3D FISH	DNA imaging scheme in single cells	Highly multiplexed detection of a genomic region of interest	Harsh treatments are required to prepare the chromatin for the FISH probes	Solovei et al. (2002)
DNase-HiC	Endonuclease DNase I replaces the restriction endonuclease	Higher effective resolution than traditional Hi-C libraries	DNase exhibits sequence bias at cleavage sites with low GC content	Ramani et al. (2016)
Micro-C	Micrococcal nuclease replaces the restriction endonuclease restriction enzymes	Able to access shorter-range interactions at higher resolution	Cannot capture long-range interactions	de Souza, (2015)
ChIP-seq	Genome-wide profiling of DNA-binding proteins, histone modifications, or nucleosomes	High resolution, low noise, great coverage, and decreased cost of sequencing	Difficulty in analyzing data owing to bias	Park, (2009)
ATAC-seq	DNA accessibility with hyperactive Tn5 transposase	Fast and sensitive detection for genome-wide chromatin accessibility	Difficult to achieve ideally cut fragments	Buenrostro et al. (2015)
ChIA-PET	Protein-centric chromatin conformation method	High-throughput detection of protein-mediated genome-wide interactions	Difficult to obtain specific antibodies for protein detection	Li et al. (2017)
HiChIP	Protein-centric chromatin conformation method	More efficient and lower input requirement than ChIA-PET; multi-scale genome architecture with greater signal to the background than in situ Hi-C	Biased signal owing to the enrichment of target binding sites	Mumbach et al. (2016)