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DTSTART;TZID=America/New_York:20191031T150000
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DTSTAMP:20210628T204253Z
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LAST-MODIFIED:20210628T204253Z
UID:554005-1572534000-1572537600@engineering.jhu.edu
SUMMARY:Thesis Proposal: Jordi Abante Llenas
DESCRIPTION:Title: Statistical Modeling and analysis of allele-specific DNA methylation at the haplotype levelAbstract: Epigenetics is the branch of biology concerned with the study of phenotypical changes due to alterations of DNA\, maintained during cell division\, excluding modifications of the sequence itself. Epigenetic information includes DNA methylation\, histone modifications\, and higher order chromatin structure among others. DNA methylation is a stable epigenetic mechanism that chemically marks the DNA by adding methyl groups at individual cytosines immediately adjacent to guanines (CpG sites). Methylation marks are used to identify cell-type specific aspects of gene regulation\, since marks located within a gene promoter or enhancer typically act to repress gene transcription\, whereas promoter or enhancer demethylation is associated with gene activation. Notably\, patterns of methylation marks are highly polymorphic and stochastic\, containing information about a broad range of normal and aberrant biological processes\, such as development and differentiation\, aging\, and carcinogenesis.The epigenetic information content of two homologous chromosomal regions need not be the same. For example\, it is well established that the ability of a cell to methylate the promoter region of a specific copy of a gene (an allele)\, is crucial for proper development. In fact\, many known phenotypical traits stem from allele-specific epigenetic marks. Moreover\, some allele-specific epigenetic differences have been found to be associated with local genetic differences between copies of a chromosome. Thus\, developing a framework for studying such epigenetic differences in diploid organisms is our main goal. More specifically\, our objective is to develop a statistical method that can be used to detect regions in the genome\, with genetic differences between homologous chromosomes\, in which there are biologically relevant differences in DNA methylation between alleles.State of the art methods for allele-specific methylation modeling and analysis have critical shortcomings rendering them unsuitable for this type of analysis. We present a statistical physics inspired model for allele-specific methylation analysis that contains a sensible number of parameters\, considering the limited sample size in whole genome bisulfite sequencing data\, which is rich enough to capture the complexity in the data. We demonstrate the appropriateness of this model for allele-specific methylation analysis using simulation data as well as real data. Using our model\, we compute mean methylation level differences between alleles\, as well as information-theoretic quantities\, such as the entropy of the methylation state in each allele and the mutual information between the methylation state and the allele of origin\, and assess the statistical significance of each quantity by learning the null distribution from the data. This complementary set of statistics allows for an unparalleled level of insight in subsequent biological analysis. As a result\, the developed framework provides an unprecedented descriptive power to characterize (i) the circumstances under which allele-specific methylation events arise\, and (ii) the cis-effect\, or lack of thereof\, that genetic mutations have on DNA methylation.
URL:https://engineering.jhu.edu/ece/event/thesis-proposal-jordi-abante-llenas/
LOCATION:Olin Hall 305\, Olin Hall 305
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