Table 1 Different Hi-C-derived methods. Optimisations indicate their modification in their protocols compared to traditional Hi-C

Traditional Hi-C

–

–

[2]

In situ Hi-C

Nuclear ligation; 4-based cutter

Allow higher resolution data generation

[3]

DNase Hi-C

DNase I to digest cross-linked DNA

Improve capture efficiency, reducing digestion bias but have A compartment bias

[77]

Micro-C

Crosslinking with DSG and micrococcal nuclease to digest cross-linked DNA

Improve capture efficiency, reducing digestion bias but have A compartment bias

[78]

BL-Hi-C

HaeIII to digest cross-linked DNA, followed by a two-step ligation

Improve capture efficiency in regulatory regions, reducing random ligation events

[79]

DLO Hi-C

No labelling and pull-down step

Reduce experimental cost

[80]

tag Hi-C

Tn5-transposase tagmentation

Focus on accessible chromatin, allow only hundreds of cells as input, reduce experimental cost

[81]

Capture HiC

RNA baits to subset specific chromatin contacts

Reduce sequencing cost, focus on a subset of interactions

[82]

Capture-C/NG Capture-C/Tiled-C

Enrich the 3C library with biotinylated capture oligonucleotides

Focus on the subset of interactions while retaining maximal library complexity

[83,84,85]

HiChIP/PLAC-seq

Chromatin Immunoprecipitation (ChIP) to subset bound chromatin contacts

Reduce sequencing cost, focus on a subset of interactions

[86, 87]

OCEAN-C

Phenol–chloroform extraction step

Focus on accessible chromatin

[88]

HiCoP

Column purified chromatin step

Focus on accessible chromatin

[89]

Methyl-HiC

Bisulfite conversion

Allow jointly profiling of DNA methylation and 3D genome structure

[90]

Hi-C 2.0

Efficient unligated ends removal

Largely reduce the dangling end DNA products

[91]

Hi-C 3.0

Double cross-linking with FA and DSG and double digestion with DpnII and DdeI

Improve the ability to identify A/B compartments and improve the enrichment of regulatory elements in loop detection

[92]