Department of Electrical Engineering and Computer Science, University of Missouri-, Columbia, MO, 65211, USA.
Sci Rep. 2019 Mar 21;9(1):4971. doi: 10.1038/s41598-019-41369-w.
Eukaryotic chromosomes are often composed of components organized into multiple scales, such as nucleosomes, chromatin fibers, topologically associated domains (TAD), chromosome compartments, and chromosome territories. Therefore, reconstructing detailed 3D models of chromosomes in high resolution is useful for advancing genome research. However, the task of constructing quality high-resolution 3D models is still challenging with existing methods. Hence, we designed a hierarchical algorithm, called Hierarchical3DGenome, to reconstruct 3D chromosome models at high resolution (<=5 Kilobase (KB)). The algorithm first reconstructs high-resolution 3D models at TAD level. The TAD models are then assembled to form complete high-resolution chromosomal models. The assembly of TAD models is guided by a complete low-resolution chromosome model. The algorithm is successfully used to reconstruct 3D chromosome models at 5 KB resolution for the human B-cell (GM12878). These high-resolution models satisfy Hi-C chromosomal contacts well and are consistent with models built at lower (i.e. 1 MB) resolution, and with the data of fluorescent in situ hybridization experiments. The Java source code of Hierarchical3DGenome and its user manual are available here https://github.com/BDM-Lab/Hierarchical3DGenome .
真核染色体通常由组织成多个尺度的成分组成，如核小体、染色质纤维、拓扑相关结构域（TAD）、染色质区室和染色体区域。因此，重建高分辨率的详细染色体 3D 模型有助于推进基因组研究。然而，使用现有方法构建高质量高分辨率 3D 模型仍然具有挑战性。因此，我们设计了一种分层算法，称为 Hierarchical3DGenome，用于在高分辨率（<=5 千碱基（KB））下重建 3D 染色体模型。该算法首先在 TAD 水平上重建高分辨率 3D 模型。然后，将 TAD 模型组装起来形成完整的高分辨率染色体模型。TAD 模型的组装由完整的低分辨率染色体模型指导。该算法成功地用于重建人类 B 细胞（GM12878）的 5KB 分辨率的 3D 染色体模型。这些高分辨率模型与较低分辨率（即 1MB）下构建的模型以及荧光原位杂交实验数据吻合良好。Hierarchical3DGenome 的 Java 源代码及其用户手册可在此处获得：https://github.com/BDM-Lab/Hierarchical3DGenome。
