TY - JOUR
T1 - SCL
T2 - A lattice-based approach to infer 3D chromosome structures from single-cell Hi-C data
AU - Zhu, Hao
AU - Wang, Zheng
N1 - Funding Information:
This work was supported by the National Institutes of General Medical Sciences Grant [R15GM120650 to Z.W.]; and start-up funding from the University of Miami (to Z.W.).
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press.
PY - 2019/10/15
Y1 - 2019/10/15
N2 - 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.
AB - 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.
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U2 - 10.1093/bioinformatics/btz181
DO - 10.1093/bioinformatics/btz181
M3 - Article
C2 - 30865261
AN - SCOPUS:85070803467
VL - 35
SP - 3981
EP - 3988
JO - Bioinformatics (Oxford, England)
JF - Bioinformatics (Oxford, England)
SN - 1367-4803
IS - 20
ER -