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    Computational Approaches for the Analysis of Chromosome Conformation Capture Data and Their Application to Study Long-Range Gene Regulation: A Dissertation

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    Authors
    Lajoie, Bryan R.
    Faculty Advisor
    Job Dekker
    Academic Program
    Bioinformatics and Computational Biology
    UMass Chan Affiliations
    Program in Systems Biology
    Document Type
    Doctoral Dissertation
    Publication Date
    2016-02-10
    Keywords
    Dissertations, UMMS
    Genomics
    Dosage Compensation, Genetic
    Gene Expression Regulation
    Sequence Analysis, RNA
    X Chromosome
    chromosome conformation capture
    3C
    genome-wide analysis
    Hi-C
    3C-seq
    genome structure
    genome function
    dosage compensation
    Bioinformatics
    Computational Biology
    Genomics
    Structural Biology
    Systems Biology
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    Abstract
    Over the last decade, development and application of a set of molecular genomic approaches based on the chromosome conformation capture method (3C), combined with increasingly powerful imaging approaches have enabled high resolution and genome-wide analysis of the spatial organization of chromosomes. The aim of this thesis is two-fold; 1), to provide guidelines for analyzing and interpreting data obtained from genome-wide 3C methods such as Hi-C and 3C-seq and 2), to leverage the 3C technology to solve genome function, structure, assembly, development and dosage problems across a broad range of organisms and disease models. First, through the introduction of cWorld, a toolkit for manipulating genome structure data, I accelerate the pace at which *C experiments can be performed, analyzed and biological insights inferred. Next I discuss a set of practical guidelines one should consider while planning an experiment to study the structure of the genome, a simple workflow for data processing unique to *C data and a set of considerations one should be aware of while attempting to gain insights from the data. Next, I apply these guidelines and leverage the cWorld toolkit in the context of two dosage compensation systems. The first is a worm condensin mutant which shows a reduction in dosage compensation in the hermaphrodite X chromosomes. The second is an allele-specific study consisting of genome wide Hi-C, RNA-Seq and ATAC-Seq which can measure the state of the active (Xa) and inactive (Xi) X chromosome. Finally I turn to studying specific gene – enhancer looping interactions across a panel of ENCODE cell-lines. These studies, when taken together, further our understanding of how genome structure relates to genome function.
    DOI
    10.13028/M2P884
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32205
    Notes

    Table 3.1, RNA-Seq Table for all genes, is available only via GEO due to size, under accession number GSE72697.

    Brian Lajoie was in the GSBS Bioinformatics and Computational Biology academic program, not the Interdisciplinary Graduate Program as stated on page 2.

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    Copyright is held by the author, with all rights reserved.
    ae974a485f413a2113503eed53cd6c53
    10.13028/M2P884
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      The Three-Dimensional Structure of the Cystic Fibrosis Locus: A Dissertation

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