Author

Hao ZhuFollow

Date of Award

Spring 2019

Degree Type

Masters Thesis

Degree Name

Master of Science (MS)

School

Computing Sciences and Computer Engineering

Committee Chair

Dr. Chaoyang Zhang

Committee Chair School

Computing Sciences and Computer Engineering

Committee Member 2

Dr. Lina Pu

Committee Member 2 School

Computing Sciences and Computer Engineering

Committee Member 3

Dr. Ras B. Pandey

Committee Member 3 School

Mathematics and Natural Sciences

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 three-dimensional structures of chromosomes based on single-cell Hi-C data.

We developed SCL (Single-Cell Lattice), a computational method to reconstruct three-dimensional (3D) structures of chromosomes based on single-cell Hi-C data. We designed a loss function and a 2D 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 3D cubic lattice. Metropolis-Hastings simulation and simulated annealing are used to simulate the structure and minimize the loss function. We evaluated the SCL-inferred 3D structures (at both 500 kb and 50 kb resolutions) using multiple criteria and compared them with the ones generated by another modeling software program. The results indicate that the 3D structures generated by SCL closely fit single-cell Hi-C data. We also found similar patterns of trans-chromosomal contact beads, Lamin-B1 enriched topological domains, and H3K4me3 enriched domains by mapping data from previous studies onto the SCL-inferred 3D structures.

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