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

Ohio State University, The, Columbus OH

Investigators

Abstract

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