DETECTING SUBTLE SEQUENCE SIGNALS IN GENOMIC JUNK

检测基因组垃圾中的细微序列信号

• 批准号: 2519133
• 负责人: Charles E Lawrence
• 金额: $ 19.02万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-20 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2519133
• 关键词: DNA binding protein; RNA binding protein; computer assisted sequence analysis; computer program /software; computer system design /evaluation; genetic regulatory element; genetic techniques; genome; mathematical model; model design /development; nucleic acid sequence; structural genes; transfer RNA

Only 3% of human genome is expected to code for proteins. The remaining 97% has been called "junk DNA". As highlighted in research news articles, several recent results indicated that there may be hidden treasure in this "junk". The highlighted findings include the discovery of regulatory signals in minisatellites, novel 3' untranslated region (3'UTR) RNA binding motifs is C-elegant Lin-14 genes and novel RNA secondary structure regulatory motifs in 5'UTRs of tRNA synthetase genes of gram-positive bacteria. The novelty of these findings leave open two important questions. Are these "grotesque deviants" or "first emissaries"? And if they are emissaries, how can their world be discovered? If these recent findings are emissaries, then their identification and characterization ill have a major impact on the next phase of the human genome project, and the numerous health benefits expected to be derived from this project. We recently described a novel method for the detection of subtle sequence signals and its application to protein sequence alignment (Lawrence, et al., 1993). The strength of this method rests on the sampling models based on the physicochemical characteristics of macromolecules and complexes. We have previously applied the predecessor of this method to the identification of gene regulation elements, but we have only begun to exploit its full potential. The main coal of this research is to adapt these methods for the identification and characterization of novel sequence signals in the non-coding regions of genomes. Specifically, we plan to adapt these methods through three developments: l) sampling models that focus on characteristics of DNA interactions in complex contexts; 2) sampling models based on the energetics of RNA/RNA interaction; and 3) a set of universally applicable enhancements. To achieve these ends, we will develop and distribute a software system for the identification and characterization of subtle sequence signals in non-coding regions of genomes.

人类基因组中只有3%的基因编码蛋白质。 其余 97%的DNA被称为“垃圾DNA”。 正如研究新闻所强调的那样， 文章，最近的一些结果表明，可能有隐藏的 在这个“垃圾”里的宝藏。 突出的发现包括 小卫星中的调节信号，新的3'非翻译区 （3 'UTR）RNA结合基序是C-优雅的Lin-14基因和新的RNA tRNA合成酶基因5 'UTR的二级结构调控基序 革兰氏阳性菌 这些发现的新奇留下了两个空白 重要的问题 这些是“怪诞的离经叛道者”还是“第一个 使者”？ 如果他们是使者，他们的世界 发现了吗如果这些最近的发现是使者，那么他们的 鉴定和定性将对下一个 人类基因组计划的第一阶段，以及众多的健康益处 预计将从该项目中获得。 我们最近描述了一部小说 一种微弱序列信号的检测方法及其应用 蛋白质序列比对（Lawrence，et al.，1993年）。 的强度 该方法依赖于基于物理化学的采样模型， 大分子和复合物的特性。我们先前已经 将该方法的前身应用于基因的鉴定 监管要素，但我们才刚刚开始充分利用其 潜力 本研究的主要目的是将这些方法应用于 新序列信号的识别和表征 基因组的非编码区。 具体来说，我们计划调整这些 方法通过三个发展：l）抽样模型，重点是 复杂背景下DNA相互作用的特征; 2）采样 基于RNA/RNA相互作用的能量学的模型;以及3）一组 普遍适用的增强。 为了实现这些目标，我们将 开发和分发用于识别的软件系统， 非编码区的细微序列信号的表征 基因组