Exonuclease combinations reduce noises in 3D genomics technologies
Siyuan Kong, Qing Li, Gaolin Zhang, Qiujia Li, Qitong Huang, Lei Huang, Hui Zhang, Yinghua Huang, Yanling Peng, Baoming Qin, Yubo Zhang
Abstract
Chromosome conformation-capture technologies are widely used in 3D genomics; however, experimentally, such methods have high-noise limitations and, therefore, require significant bioinformatics efforts to extract reliable distal interactions. Miscellaneous undesired linear DNAs, present during proximity-ligation, represent a main noise source, which needs to be minimized or eliminated. In this study, different exonuclease combinations were tested to remove linear DNA fragments from a circularized DNA preparation. This method efficiently removed linear DNAs, raised the proportion of annulation and increased the valid-pairs ratio from ∼40% to ∼80% for enhanced interaction detection in standard Hi-C. This strategy is applicable for development of various 3D genomics technologies, or optimization of Hi-C sequencing efficiency.