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

Genome Biol. 2021 Jul 27;22(1):217. doi: 10.1186/s13059-021-02435-7.

Abstract

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.

Keywords: 3D genome; Hi-C; Single cell; TAD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Animals
  • CCCTC-Binding Factor / genetics
  • CCCTC-Binding Factor / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromatin / chemistry*
  • Chromatin Assembly and Disassembly*
  • Cluster Analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Entropy
  • Gene Expression
  • Genome*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Mammals
  • Single-Cell Analysis / methods*
  • Software*

Substances

  • CCCTC-Binding Factor
  • CTCF protein, human
  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • RAD21 protein, human