ATD: Statistical Methods and Software for Analyzing Massively Parallel Epigenomic Sequencing Data

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The dawn of the massively parallel sequencing technology has propelledresearch in epigenetics, from genome-wide methylation profiling,histone modification patterns clustering, to identifying generegulation through spatial interactions. The power of epigeneticshas already been felt, such as its use in making drugs for treatingseveral diseases, but unfortunately, it has also been recognized thatit may be exploited for the bad. The powerful, rapidly acquirable,stable, and heritable features of epigenetic could be a perfect vehiclefor bio-terrorism. The regulatory mechanism of gene expression maybe altered based on the epigenetic principle to create mutant cellswith devastating consequences very quickly. To counter the potentialof such threat, the detection of changes in epigenetic marks is akey issue. This project aims to develop likelihood based as wellas Bayesian methodology, computational algorithms and associatedsoftware for analyzing massively parallel epigenomic sequencing datathat are tangible for detection of biological threats. The focus willbe on chromatin signature and structure analysis to study histonebinding patterns in promoters and enhancers and spatial interactionsbetween promoters and enhancers within a protein complex. Methods andalgorithms developed will be implemented in three software packages:DIME, ChAPE, and BASIC. It is anticipated that the analytical toolsdeveloped will contribute to uncover global host-response epigeneticpatterns.Charles Darwin's publication of "On the origin of species" 150 yearsago has taught us that evolutionary changes take many generationsof natural selection. In recent years, however, a new scientificarea called epigenetics is helping to usher in a paradigm shift. Itis hypothesized, based on amassed scientific evidence, that powerfulenvironmental conditions may leave an imprint on the genetic material,which can lead to passage of new traits in a single generationthrough the epigenetic process. The importance of epigenetics hasbeen recognized in the scientific community, and indeed, epigeneticshas been used for the good, such as its utilization for producing drugsfor treating complex diseases. Unfortunately, it may also be exploitedby bio-terrorists. In other words, gene regulation mechanism may bealtered to create mutant cells, which could pose great threats withdevastating consequence. Anticipating the potential of such type ofthreats, this project proposes statistical methods and computationalalgorithms to analyze epigenetic data from advanced genomic sequencingtechnology to detect mutant cells that may have gone through epigeneticchanges. These tools are anticipated to contribute to early detectionof exposure to potential biowarfare pathogen. This project will alsocontribute to the training of the next generation of researchers ina cutting-edge interdisciplinary research area that fuses knowledgein biology, statistics and computer science.