Hi-C is a popular technique to map three-dimensional chromosome conformation. In principle, Hi-C’s resolution is only limited by the size of restriction fragments. However, insufficient sequencing depth forces researchers to artificially reduce the resolution of Hi-C matrices at a loss of biological interpretability. We present the Hi-C Interaction Frequency Inference (HIFI) algorithms that accurately estimate restriction-fragment resolution Hi-C matrices by exploiting dependencies between neighboring fragments. Cross-validation experiments and comparisons to 5C data and known regulatory interactions demonstrate HIFI’s superiority to existing approaches. In addition, HIFI’s restriction-fragment resolution reveals a new role for active regulatory regions in structuring topologically associating domains.

中文翻译：

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HIFI：根据限制性片段分辨率的 Hi-C 数据估计 DNA-DNA 相互作用频率


Hi-C 是一种绘制三维染色体构象的流行技术。原则上，Hi-C 的分辨率仅受限制性片段大小的限制。然而，测序深​​度不足迫使研究人员人为降低 Hi-C 矩阵的分辨率，从而丧失生物学可解释性。我们提出了 Hi-C 相互作用频率推断 (HIFI) 算法，该算法通过利用相邻片段之间的依赖性来准确估计限制性片段分辨率 Hi-C 矩阵。交叉验证实验以及与 5C 数据和已知监管相互作用的比较证明了 HIFI 相对于现有方法的优越性。此外，HIFI 的限制性片段解析揭示了活性调控区域在构建拓扑关联域中的新作用。