CAREER: A Computational Framework to Study Epigenetic Regulation

这项工作将开发一个计算框架，以促进对表观遗传基因调控的理解。理解表观基因组在基因调控和表型发育中的作用是现代分子生物学最重要的任务之一。随着目前基因组规模的表观遗传修饰数据的前所未有的可用性，该项目将开发计算算法和工具来模拟组蛋白修饰，并发现对基因调控感兴趣的模式。已发现的组蛋白修饰模式将为我们提供对多重表观遗传修饰相互作用和基因组-表观基因组相互作用的深刻见解。从大规模基因组学和表观基因组数据集成构建的基因表达调控概率模型将极大地促进对基因调控在不同水平上的理解。这项研究的目标是：(1)从高通量测序数据中创建新的算法来模拟表观遗传修饰；(2)创建计算和统计算法来挖掘表观遗传修饰模式；以及(3)通过基因组和表观基因组数据整合来建模基因调控。表观遗传学是研究由潜在DNA序列变化以外的机制引起的基因表达或细胞表型的可遗传变化。这项工作将开发用于模拟表观遗传变化的工具。所有拟议的研究都将转化为软件工具，作为开放源码和免费提供给科学界的软件工具发布。所有相关的源代码将通过项目网站向公众免费提供。这项拟议的研究将对各级教育产生重大影响。这项研究将纳入研究生、本科生和K12教育，并将向研究界、非正规科学教育和公众传播，以增进科学理解。教育和外联部分还包括在跨学科科学领域为妇女和女童开展外联活动。

This work will develop a computational framework to advance the understanding of epigenetic gene regulation. One of the most important tasks in modern molecular biology is to understand the role of epigenome in gene regulation and in phenotype development. With the current unprecedented availability of genome-scale epigenetic modification data, this project will develop computational algorithms and tools to model histone modification and discover patterns that are of interest to gene regulation. The discovered histone modification patterns will provide us deep insights into multiple epigenetic modification interaction and genome-epigenome interaction. The probabilistic model of gene expression regulation constructed from large-scale genomics and epigenomic data integration will greatly advance understanding of gene regulation at different levels. The objectives of this research are to: (1) create novel algorithms to model epigenetic modifications from high-throughput sequencing data; (2) create computational and statistical algorithms to mine epigenetic modification patterns; and (3) model gene regulation through genomic and epigenomic data integration.Epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. This work will develop tools for modeling epigenetic changes. All of the proposed research will be converted into software tools that will be released as open-source and freely available software tools to the scientific community. All the associated source code will be freely available to the public through the project website. The proposed research will have great impact on education at all levels. The research will be incorporated into the graduate, undergraduate and K12 education, and will be disseminated to the research community, informal science education, and the public to enhance scientific understanding. The education and outreach component also includes developing outreach activities for women and girls in interdisciplinary science.