Scalvini Barbara, Schiessel Helmut, Golovnev Anatoly, Mashaghi Alireza
Medical Systems Biophysics and Bioengineering, Leiden Academic Centre for Drug Research, Faculty of Science, Leiden University, Einsteinweg 55, 2333CC Leiden, the Netherlands.
Centre for Interdisciplinary Genome Research, Faculty of Science, Leiden University, Einsteinweg 55, 2333CC Leiden, the Netherlands.
iScience. 2022 Feb 5;25(3):103866. doi: 10.1016/j.isci.2022.103866. eCollection 2022 Mar 18.
Reciprocal regulation of genome topology and function is a fundamental and enduring puzzle in biology. The wealth of data provided by Hi-C libraries offers the opportunity to unravel this relationship. However, there is a need for a comprehensive theoretical framework in order to extract topological information for genome characterization and comparison. Here, we develop a toolbox for topological analysis based on Circuit Topology, allowing for the quantification of inter- and intracellular genomic heterogeneity, at various levels of fold complexity: pairwise contact arrangement, higher-order contact arrangement, and topological fractal dimension. Single-cell Hi-C data were analyzed and characterized based on topological content, revealing not only a strong multiscale heterogeneity but also highly conserved features such as a characteristic topological length scale and topological signature motifs in the genome. We propose that these motifs inform on the topological state of the nucleus and indicate the presence of active loop extrusion.
基因组拓扑结构与功能的相互调控是生物学中一个基本且长期存在的谜题。Hi-C文库提供的大量数据为解开这种关系提供了契机。然而，需要一个全面的理论框架来提取用于基因组表征和比较的拓扑信息。在此，我们基于电路拓扑开发了一个用于拓扑分析的工具箱，能够在不同折叠复杂度水平下对细胞间和细胞内的基因组异质性进行量化：成对接触排列、高阶接触排列以及拓扑分形维数。基于拓扑内容对单细胞Hi-C数据进行了分析和表征，不仅揭示了强烈的多尺度异质性，还发现了高度保守的特征，如基因组中特征性的拓扑长度尺度和拓扑特征基序。我们提出，这些基序反映了细胞核的拓扑状态，并表明存在活跃的环挤压。
