Journal
ISCIENCE
Volume 25, Issue 3, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2022.103866
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Funding
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [EXC 2068-390729961]
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A toolbox for topological analysis based on Circuit Topology has been developed in this study, allowing for the quantification of inter- and intracellular genomic heterogeneity. The analysis of single-cell Hi-C data reveals highly conserved topological features that inform on the topological state of the nucleus and indicate the presence of active loop extrusion.
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.
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