Date of Award

Summer 2020

Degree Type

Dissertation

School

Computing Sciences and Computer Engineering

Committee Chair

Chaoyang Zhang

Committee Chair School

Computing Sciences and Computer Engineering

Committee Member 2

Ras B. Pandey

Committee Member 2 School

Computing Sciences and Computer Engineering

Committee Member 3

Lina Pu

Committee Member 3 School

Computing Sciences and Computer Engineering

Committee Member 4

Zhaoxian Zhou

Committee Member 4 School

Computing Sciences and Computer Engineering

Committee Member 5

Nan Wang

Committee Member 5 School

Computing Sciences and Computer Engineering

Abstract

Reconstructing 3D chromosomal structures based on single-cell Hi-C data is a challenging scientific problem due to the extreme sparseness of the single-cell Hi-C data. In this research, we used the Lennard-Jones potential to reconstruct both 500 kb and highresolution 50 kb structures for chromosomes based on single-cell Hi-C data. A chromosome was represented by a string of 500 kb or 50 kb DNA beads and put into a 3D cubic lattice for simulations. A 2D Gaussian function was used to impute the sparse singlecell Hi-C contact matrices. We designed a novel loss function based on the Lennard-Jones potential, in which the �� value, that is, the well depth of the Lennard-Jones potential was used to indicate how strong a pair of beads bind. For the bead pairs with a single-cell Hi-C contact or the bead pairs that are close to other bead pairs having single-cell Hi-C contacts, the loss function assigns them a stronger binding stability. Metropolis Hasting was used to try different locations for the DNA beads; and simulated annealing was used to optimize the loss function. We proved the correctness and validness of the reconstructed 3D structures by evaluating the models according to multiple criteria and comparing the models with the 3D-FISH data.

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