IIBR Informatics: An integrative study of distal gene regulation

了解调控复杂基因表达的因素在生物学研究中是必不可少的。蛋白质编码基因的时空活动受基因组序列的控制，而基因组序列一般远离其对应的受控靶基因。调控区与相应的靶基因相互作用，显著增强或抑制靶基因的活性。尽管几十年的奋进对这些远端控制元件的研究，在特定的实验条件下，他们的靶基因的知识仍然是有限的。因此，该项目提出创建计算方法和工具，以填补这一空白，通过识别哺乳动物基因组中的蛋白质编码基因的远端控制开关。该项目将涉及研究生、本科生和高中生，通过研讨会、会议、论文、工具、网站等传播研究成果。开发的方法和工具将对哺乳动物基因组的注释和对人类健康的理解至关重要。鉴于实验方法往往成本高昂，现有计算方法的性能仍不理想，该项目将通过以下两个主要研究目标开发新的计算方法和工具，用于识别哺乳动物基因组远端调控区的靶基因：（i）创建推断远端区域与其靶基因之间相互作用的限制的计算方法和工具;以及（ii）创建预测远端调控区的靶基因的计算方法和工具。这些目标的实现将极大地推动基因转录调控和哺乳动物基因组注释的研究。该项目还有教育目标，包括：（一）指导少数民族高中生;（二）教育毕业生和本科生;（三）传播研究发现。这些教育活动将与拟议的研究活动很好地结合起来。该项目的成果可以在www.example.com上找到http://www.cs.ucf.edu/~xiaoman/ETThis奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

Understanding the factors regulating complex gene expression is essential in biological research. The temporal and spatial activities of protein coding genes are controlled by genome sequences which are in general far from their corresponding controlled target genes. The controlling regions interact with their corresponding target genes and significantly strength or repress the activities of these target genes. Despite of decades of endeavor towards studying these distal controlling elements, knowledge of their target genes under specific experimental conditions is still limited. This project thus proposes to create computational methods and tools to fill this gap by identifying distal controlling switches of protein coding genes in the mammalian genomes. The project will involve graduate students, undergraduates, and high school students, disseminate research results through seminars, conferences, papers, tools, websites, etc. The developed methods and tools will be essential for the annotation of mammalian genomes and understanding of human health.Given experimental methods tend to be costly and performance of available computational methods is still suboptimal, this project will develop novel computational methods and tools for the identification of the target genes of distal regulatory regions in mammalian genomes through achieving the following two main research goals: (i) creating computational methods and tools to infer the constraints of interactions between distal regions and their target genes; and (ii) creating computational methods and tools to predict the target genes of distal regulatory regions. The fulfillment of these goals will significantly advance the studies on gene transcriptional regulation and the annotation of mammalian genomes. The project also has educational goals including: (i) mentoring minority high school students; (ii) educating graduates and undergraduates; and (iii) disseminating research discoveries. These educational activities will be well integrated with the proposed research activities. The results from this project can be found at http://www.cs.ucf.edu/~xiaoman/ETThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.