Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Faculty of Physics, Lomonosov Moscow State University, Moscow, Russia.
PLoS Comput Biol. 2021 Nov 18;17(11):e1009546. doi: 10.1371/journal.pcbi.1009546. eCollection 2021 Nov.
Construction of chromosomes 3D models based on single cell Hi-C data constitute an important challenge. We present a reconstruction approach, DPDchrom, that incorporates basic knowledge whether the reconstructed conformation should be coil-like or globular and spring relaxation at contact sites. In contrast to previously published protocols, DPDchrom can naturally form globular conformation due to the presence of explicit solvent. Benchmarking of this and several other methods on artificial polymer models reveals similar reconstruction accuracy at high contact density and DPDchrom advantage at low contact density. To compare 3D structures insensitively to spatial orientation and scale, we propose the Modified Jaccard Index. We analyzed two sources of the contact dropout: contact radius change and random contact sampling. We found that the reconstruction accuracy exponentially depends on the number of contacts per genomic bin allowing to estimate the reconstruction accuracy in advance. We applied DPDchrom to model chromosome configurations based on single-cell Hi-C data of mouse oocytes and found that these configurations differ significantly from a random one, that is consistent with other studies.
基于单细胞 Hi-C 数据构建染色体 3D 模型是一个重要的挑战。我们提出了一种重建方法 DPDchrom，它整合了关于所重建构象应该是卷曲状还是球状以及接触点处的弹簧松弛的基本知识。与之前发表的协议不同，由于存在明确的溶剂，DPDchrom 可以自然形成球状构象。在人工聚合物模型上对该方法和其他几种方法进行基准测试表明，在高接触密度下具有相似的重建准确性，而在低接触密度下 DPDchrom 具有优势。为了在不考虑空间方向和比例的情况下比较 3D 结构，我们提出了改进的杰卡德指数。我们分析了两种接触缺失的来源：接触半径变化和随机接触采样。我们发现，每个基因组 bin 的接触数与重建准确性呈指数相关，这允许提前估计重建准确性。我们将 DPDchrom 应用于基于小鼠卵母细胞单细胞 Hi-C 数据的染色体构象模型，发现这些构象与随机构象有显著差异，这与其他研究一致。
