Computational Models and Algorithms for Nucleosome Positioning

The dissertation research is focused on improving performance on genome wide nucleosome positioning. Nucleosome is the basic structural unit of DNA in eukaryotic cells. As nucleosomes limit the accessibility of the wrapped DNA to transcription factors and other DNA-binding proteins, their positions play an essential role in regulations of gene activities. Experiments have indicated that DNA sequence strongly influences nucleosome positioning by enhancing or reducing their binding ability to nucleosomes, therefore providing an intrinsic cell regulatory mechanism. While some sequence features are known to be nucleosome forming or nucleosome inhibiting, however, existing models have limited accuracy in predicting quantitatively nucleosomes occupancy (i.e., statistical nucleosome positioning) based on DNA sequence. The study developed several algorithms to produce better features as well as more accuracy models to predict nucleosome positioning. It first proposed several models to classify a given DNA sequence as nucleosome forming sequence or nucleosome inhibiting sequence. Then, it turns the focus to predict the probability that a basepair is covered by any nucleosome. Moreover, based on a one basepair dataset, it found an intrinsic pattern which can be used to develop a single base pair nucleosome localization algorithm. Experimental results have shown the proposed methods are comparable or better than all existing solutions.