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Table 1 Advantages and disadvantages of current 3D genome technologies

From: From association to mechanism in complex disease genetics: the role of the 3D genome

Technique Assay name/description Target size Assay platform Cell input Advantages Disadvantages References
 3C Chromosome conformation capture One target Quantitative PCR > 100 M • Quantitative measurement of long-range interactions between two targeted loci
• No sequencing required
• Low throughput
• Large amount of input cells
[34, 35]
 4C Circular chromosome conformation capture or chromosome conformation capture-on-chip Multiple targets Microarray > 100 M • Identification of multiple DNA regions that interact with a target locus
• Modified protocol: 4C-seq
• Relatively low throughput
• Large amount of input cells
[40, 63]
 5C Chromosome conformation carbon copy Multiple targets Microarray or sequencing > 100 M • Multiplexed conformation capture
• Higher efficiency and lower background compared to 3C
• Not all sites are compatible to 5C primer design
• 5C cannot detect contacts larger than a few megabases
 Capture-C 3C with specific oligonucleotides capture Multiple targets Sequencing 10-20 M • Unbiased capture of all regions interacting with a specific target sequence
• Reduced background signal compared to Hi-C
• More informative contacts
• Modified protocol: Capture Hi-C
• Interaction detection depends on the design of the target “bait” [42]
 Non-protein-mediated Hi-C Chromosome conformation capture by high-throughput sequencing All interactions Sequencing 20-25 M • High throughput
• Improved efficiency
• First genome-wide assay
• Modified protocol: in situ Hi-C; single cell Hi-C
• High background due to random ligations
• Requires deep sequencing
• Relatively low resolution
[21, 44,45,46,47,48]
 Protein-mediated ChIA-PET Chromatin interaction analysis by paired-end tag sequencing All interactions Sequencing > 100 M • Identify specific protein-mediated DNA loop structures
• Reduced background noise in sequencing data
• Long processing time (> 6 days)
• Requires high efficiency ChIP-grade antibodies
In situ Hi-C with protein-centric ChIP/proximity ligation-assisted ChIP-seq All interactions Sequencing 1-10 M • Faster protocol (2 days)
• Higher efficiency than ChIA-PET
• Less sequencing
• Requires high efficiency ChIP-grade antibodies [50,51,52]