DeTOKI identifies and characterizes the dynamics of chromatin TAD-like domains in a single cell

• Published in: Genome Biology Vol. 22; no. 1; p. 217
• Main Authors: Li, Xiao, Zeng, Guangjie, Li, Angsheng, Zhang, Zhihua
• Format: Journal Article
• Language: English
• Published: London BioMed Central 27.07.2021; BMC
• Subjects: 3D genome; Algorithms; Animal Genetics and Genomics; Animals; Bioinformatics; Biomedical and Life Sciences; CCCTC-Binding Factor - genetics; CCCTC-Binding Factor - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Chromatin; Chromatin - chemistry; Chromatin Assembly and Disassembly; Chromosomes; Cluster Analysis; Decomposition; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Entropy; Evolutionary Biology; Gene Expression; Genome; Genomes; Hi-C; Histones - genetics; Histones - metabolism; Human Genetics; Humans; Life Sciences; Mammals; Microbial Genetics and Genomics; Plant Genetics and Genomics; Single cell; Single-Cell Analysis - methods; Software; Sparsity; TAD; Single cell; 3D genome; Hi-C; TAD
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-021-02435-7

Topologically associating domains (TAD) are a key structure of the 3D mammalian genomes. However, the prevalence and dynamics of TAD-like domains in single cells remain elusive. Here we develop a new algorithm, named deTOKI, to decode TAD-like domains with single-cell Hi-C data. By non-negative matrix factorization, deTOKI seeks regions that insulate the genome into blocks with minimal chance of clustering. deTOKI outperforms competing tools and reliably identifies TAD-like domains in single cells. Finally, we find that TAD-like domains are not only prevalent, but also subject to tight regulation in single cells.