Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, Moores Cancer Center and Institute of Genomic Medicine, UCSD School of Medicine, La Jolla, CA 92093, USA.
Cell Syst. 2019 Jun 26;8(6):494-505.e14. doi: 10.1016/j.cels.2019.05.011.
Recent whole-genome mapping approaches for the chromatin interactome have offered new insights into 3D genome organization. However, our knowledge of the evolutionary patterns of 3D genome in mammals remains limited. In particular, there are no existing phylogenetic-model-based methods to analyze chromatin interactions as continuous features. Here, we develop phylogenetic hidden Markov random field (Phylo-HMRF) to identify evolutionary patterns of 3D genome based on multi-species Hi-C data by jointly utilizing spatial constraints among genomic loci and continuous-trait evolutionary models. We used Phylo-HMRF to uncover cross-species 3D genome patterns based on Hi-C data from the same cell type in four primate species (human, chimpanzee, bonobo, and gorilla). The identified evolutionary patterns of 3D genome correlate with features of genome structure and function. This work provides a new framework to analyze multi-species continuous genomic features with spatial constraints and has the potential to help reveal the evolutionary principles of 3D genome organization.
近年来，用于染色质互作组的全基因组作图方法为三维基因组结构提供了新的见解。然而，我们对哺乳动物三维基因组的进化模式的了解仍然有限。特别是，目前还没有基于系统发育模型的方法来分析作为连续特征的染色质相互作用。在这里，我们开发了系统发育隐马尔可夫随机场（Phylo-HMRF），通过联合利用基因组位点之间的空间约束和连续特征进化模型，基于多物种 Hi-C 数据来识别三维基因组的进化模式。我们使用 Phylo-HMRF 根据来自四个灵长类物种（人类、黑猩猩、倭黑猩猩和大猩猩）的相同细胞类型的 Hi-C 数据来揭示跨物种的三维基因组模式。鉴定出的三维基因组进化模式与基因组结构和功能特征相关。这项工作为分析具有空间约束的多物种连续基因组特征提供了一个新的框架，并有可能帮助揭示三维基因组组织的进化原则。
