Dataset Information

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

ABSTRACT: MOTIVATION: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.

SUBMITTER: Zhu H

PROVIDER: S-EPMC6792089 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Zhu Hao H Wang Zheng Z

Bioinformatics (Oxford, England) 20191001 20

<h4>Motivation</h4>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.<h4>Results</h4>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 functi ...[more]

PMID: 30865261

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Project description:BackgroundThe three-dimensional (3D) structure of chromatin has a massive effect on its function. Because of this, it is desirable to have an understanding of the 3D structural organization of chromatin. To gain greater insight into the spatial organization of chromosomes and genomes and the functions they perform, chromosome conformation capture (3C) techniques, particularly Hi-C, have been developed. The Hi-C technology is widely used and well-known because of its ability to profile interactions for all read pairs in an entire genome. The advent of Hi-C has greatly expanded our understanding of the 3D genome, genome folding, gene regulation and has enabled the development of many 3D chromosome structure reconstruction methods.ResultsHere, we propose a novel approach for 3D chromosome and genome structure reconstruction from Hi-C data using Particle Swarm Optimization (PSO) approach called ParticleChromo3D. This algorithm begins with a grouping of candidate solution locations for each chromosome bin, according to the particle swarm algorithm, and then iterates its position towards a global best candidate solution. While moving towards the optimal global solution, each candidate solution or particle uses its own local best information and a randomizer to choose its path. Using several metrics to validate our results, we show that ParticleChromo3D produces a robust and rigorous representation of the 3D structure for input Hi-C data. We evaluated our algorithm on simulated and real Hi-C data in this work. Our results show that ParticleChromo3D is more accurate than most of the existing algorithms for 3D structure reconstruction.ConclusionsOur results also show that constructed ParticleChromo3D structures are very consistent, hence indicating that it will always arrive at the global solution at every iteration. The source code for ParticleChromo3D, the simulated and real Hi-C datasets, and the models generated for these datasets are available here: https://github.com/OluwadareLab/ParticleChromo3D.

Dataset Information

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

Publications

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

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