Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/43592
Title: Study of protein-DNA interaction using new generation data
Authors: ZHANG ZHIZHUO
Keywords: protein-DNA interaction,motif finding, Hi-C, 3D chromosome structure, ChIP-seq
Issue Date: 25-Jan-2013
Source: ZHANG ZHIZHUO (2013-01-25). Study of protein-DNA interaction using new generation data. ScholarBank@NUS Repository.
Abstract: Understanding how proteins interact with DNA is essential for decoding many biological processes and disease states. There are two different levels to study how proteins bind on DNA: sequence level and structure level. From sequence to structure level, the area of protein DNA interaction has been fueled by many new technologies and by breakthroughs in chromatin immunoprecipitation (ChIP) technology, parallel-sequencing technology and chromosome conformation capture (3C) technology, such as ChIP-chip, ChIP-seq (sequence level) and Hi-C, ChIA-PET(structure level). The data of the new technologies leads to many novel bioinformatics problems. This thesis focus on three topics: (1) Motif Enrichment Analysis using ChIP-seq data (2) De novo Motif Analysis using ChIP-seq data.(3) Reconstructing three-dimensional Chromosome using Hi-C data. A novel parameter-free method called CENTDIST is developed to assess motif enrichment by utilizing center distribution property from the ChIP-seq data. For de novo motif finding, a novel EM(expectation maximization)-based program called SEME is developed to learn different positional bias and sequence rank bias for different motifs by estimating the parameters in a mixture model. Last but not least, a semi-definite programming (SDP) based algorithm called ChromSDE is developed to recover the correct 3D chromosome structure using Hi-C data. In summary, the methods developed in this thesis have unlocked the potential provided by the new generation sequencing data of Protein-DNA interaction and gave more in-depth understanding for biological mechanism compared to the existing methods.
URI: http://scholarbank.nus.edu.sg/handle/10635/43592
Appears in Collections:Ph.D Theses (Open)

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