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METHODS AND ANALYSES IN THE STUDY OF HUMAN DNA METHYLATION

Hu, Ke
http://rave.ohiolink.edu/etdc/view?acc_num=case1522760441838452

Abstract Details

2018, Doctor of Philosophy, Case Western Reserve University, EECS - Computer and Information Sciences.
DNA methylation is an important epigenetic mechanism. Analysis of DNA methylation patterns will help understand mechanism and function of DNA methylation and diseases associated with it. Advancements of technology increase both depth and breadth of DNA methylation measurement, make it possible to detect multi-modal CpG sites, capture DNA methylation co-occurrence patterns and profile genome-wide allele-specific DNA methylation (ASM) patterns from different types of data. In this dissertation, we will describe novel tools and methods designed for analyzing human DNA methylation data. DNA methylation beadchip assay enables study in population level. We have developed a Gaussian Mixture-Model Clustering (GMMC) based approach to systematically detect CpG sites with multi-modal methylation level distributions (mmCpGs) across the genome based on Ilumina 450k data. Comparison with an existing approach has illustrated that our GMMC based method is more accurate and consistent. Ultra-deep bisulfite sequencing allows more than ten thousand depth of coverage of certain genomic regions. We developed BSPAT, an efficient and user friendly tool to discover and visualize DNA methylation co-occurrence patterns from ultra-deep bisulfite sequencing datasets. Besides, BSPAT can identify potential ASM patterns from co-occurrence patterns with SNP inside. Recently, Whole Genome Bisulfite Sequencing (WGBS) makes it possible to study DNA methylation in single nucleotide level genome-widely. We have developed a novel computational method to better detect ASM regions from WGBS data and have performed comprehensive analysis of their distributions by applying the method on WGBS datasets from eight human cell lines. Results have shown ASM regions is ubiquitous and functional in human genome. Our findings confirm previous observations that ASM can be found in most imprinted genes and on female X chromosome. Our method is highly reliable with very low false positive rates and the partition of reads in predicted ASMs is in high concordance with the two alleles when ASMs overlap heterozygous SNPs. Based on our previous work, we have implemented a general bisulfite sequence clustering tool called BS-Cluster. It released requirement and setup in BSPAT and ASM profiling, thus generally can be applied on any kind of bisulfite-sequencing dataset, including both ultra-deep bisulfite sequencing and WGBS.
Jing Li (Committee Chair)
Angela Ting (Committee Member)
Fulai Jin (Committee Member)
Xusheng Xiao (Committee Member)
145 p.
Bioinformatics; Computer Science; Genetics
DNA methylation, Bisulfite sequencing, allele-specific DNA methylation

Recommended Citations

Citations

  • Hu, K. (2018). METHODS AND ANALYSES IN THE STUDY OF HUMAN DNA METHYLATION [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1522760441838452

    APA Style (7th edition)

  • Hu, Ke. METHODS AND ANALYSES IN THE STUDY OF HUMAN DNA METHYLATION. 2018. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1522760441838452.

    MLA Style (8th edition)

  • Hu, Ke. "METHODS AND ANALYSES IN THE STUDY OF HUMAN DNA METHYLATION." Doctoral dissertation, Case Western Reserve University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1522760441838452

    Chicago Manual of Style (17th edition)

case1522760441838452
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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.