SCL: A lattice-based approach to infer 3D chromosome structures from single-cell Hi-C data

Hao Zhu, Zheng Wang, Alfonso Valencia

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

In contrast to population-based Hi-C data, single-cell Hi-C data are zero-inflated and do not indicate the frequency of proximate DNA segments. There are a limited number of computational tools that can model the 3D structures of chromosomes based on single-cell Hi-C data. Results: We developed single-cell lattice (SCL), a computational method to reconstruct 3D structures of chromosomes based on single-cell Hi-C data. We designed a loss function and a 2 D Gaussian function specifically for the characteristics of single-cell Hi-C data. A chromosome is represented as beads-on-a-string and stored in a 3 D cubic lattice. Metropolis-Hastings simulation and simulated annealing are used to simulate the structure and minimize the loss function. We evaluated the SCL-inferred 3 D structures (at both 500 and 50 kb resolutions) using multiple criteria and compared them with the ones generated by another modeling software program. The results indicate that the 3 D structures generated by SCL closely fit single-cell Hi-C data. We also found similar patterns of trans-chromosomal contact beads, Lamin-B1 enriched topologically associating domains (TADs), and H3K4me3 enriched TADs by mapping data from previous studies onto the SCL-inferred 3 D structures. Availability and implementation: The C++ source code of SCL is freely available at http://dna.cs.miami.edu/SCL/. Supplementary information: Supplementary data are available at Bioinformatics online.

Original languageEnglish (US)
Pages (from-to)3981-3988
Number of pages8
JournalBioinformatics
Volume35
Issue number20
DOIs
StatePublished - Oct 15 2019

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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