Maintenance and Development of RepeatMasker and RepeatModeler

RepeatMasker和RepeatModeler的维护和开发

• 批准号: 8235956
• 负责人: Arian Fredericus Anthonius Smit
• 金额: $ 39.77万
• 依托单位: INSTITUTE FOR SYSTEMS BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8235956
• 关键词: Algorithms; Amino Acid Sequence; Animals; Bioinformatics; Birds; Classification; Code; Complex; Computer software; Consensus; Consensus Sequence; DNA; DNA Maintenance; DNA Transposable Elements; Databases; Detection; Development; Elements; Evolution; Family; Genbank; Genome; Genomics; Grant; Hereditary Disease; Human Genome; Label; Length; Libraries; Link; Maintenance; Masks; Metadata; Mutation; Organism; Output; Peptide Sequence Determination; Performance; Phylogenetic Analysis; Phylogeny; Population Study; Process; Property; Protein Databases; Quality Control; Research; Resources; Sequence Analysis; Series; Source Code; Speed; Time; United States National Institutes of Health; Use of New Techniques; Variant; base; computerized tools; design; genome sequencing; homologous recombination; improved; mammalian genome; open source; programs; public health relevance; tool; web page; web site

DESCRIPTION (provided by applicant): Most eukaryotic genomes include vast numbers of interspersed repeats (IRs), which are the remnants of mostly selfishly amplified transposable elements. Transposable elements have an exceptionally wide-ranging mutagenic effect on genomes, while recognition of IRs provide unparalleled information on genome evolution and is crucial in many aspects of bioinformatics. This grant would continue support for the maintenance and further development of RepeatMasker, a computational tool that has become the de facto standard for identification and characterization of IRs, and support the development of RepeatModeler, a program designed to derive RepeatMasker-grade databases of IR consensus sequences. The source codes for these tools are freely available to the public. Development will emphasize the following: a) As sequencing of new vertebrate species continues to accelerate, further development of the de novo repeat identifying program RepeatModeler is a priority. Unlike other such programs in development, RepeatModeler is specifically geared for the analysis of mammalian and bird genomes. b) Now the RepeatMasker code has been completely refactored, the emphasis of its development shifts towards increasing its sensitivity and accuracy, and addition of options like a mode for analyzing low coverage assemblies and recognition of chimaeric elements created by homologous recombinations. c) The maintenance of the DNA consensus sequence database with many RepeatMasker-specific metadata, the Transposable Element protein database, and the website with, among others, a growing number of pre-annotated genomes, will take an effort that is more likely to grow than to shrink in size. d) We aim to further automate and refine the process of "phylogenetic labeling" of consensus sequences in the library, and to expand the databases with refined sets of subfamily sequences, which will make the prediction of potentially polymorphic elements and the precise time of older insertions possible. As part of our efforts to increase the sensitivity and speed of the RepeatMasker program, we propose to develop an improved search engine, starting from the open source BLASTZ code. PUBLIC HEALTH RELEVANCE: RepeatMasker is the default tool to annotate the repetitive portion of complex genomes like the human genome, which is an essential and standard process in any genomic sequence analysis. In recent years it has become clear that interspersed repeats are responsible for a large fraction of "copy number" or structural allelic variations like large deletions, duplications and insertion of foreign DNA, which are far more common than previously assumed and are much more likely than small mutations to be associated with phenotypic differences and genetic diseases.

描述（由申请人提供）：大多数真核基因组都包括大量散布的重复序列（IRS），这些重复序列是大多数自私放大的转座元素的残余物。转座元素对基因组具有异常广泛的诱变作用，而对IRS的识别则提供了有关基因组进化的无与伦比的信息，并且在生物信息学的许多方面至关重要。该赠款将继续支持ReponMasker的维护和进一步开发，ReponMasker是一种计算工具，已成为IRS识别和表征的事实上的标准，并支持ReponModeler的开发，该计划旨在得出IR共识序列的ReponMasker级数据库。这些工具的源代码可供公众免费使用。开发将强调以下内容：a）随着新脊椎动物的测序继续加速，从头重复识别程序重复模型的进一步发展是一个优先事项。与开发中的其他此类程序不同，重复模型专门用于分析哺乳动物和鸟类基因组。 b）现在已经完全重构了重复验证码，其发展的重点转向提高其敏感性和准确性，并添加了诸如分析低覆盖范围组件的模式以及对同源重组产生的嵌合元件的识别的模式。 c）维持DNA共识序列数据库，其中许多重复验证者特异性元数据，可转座元素蛋白质数据库以及带有越来越多的预通量基因组的网站将采取的努力比缩小大小更可能成长。 d）我们的目标是进一步自动化和完善图书馆共识序列的“系统发育标记”的过程，并使用精致的亚家族序列扩展数据库，这将使潜在的多态性元素和较旧插入的精确时间的预测成为可能。作为提高ReponMasker程序的灵敏度和速度的努力的一部分，我们建议从开源Blastz代码开始开发改进的搜索引擎。 公共卫生相关性：ReponMasker是注释复杂基因组（如人类基因组）的重复部分的默认工具，这是任何基因组序列分析中的必不可少的和标准过程。近年来，很明显，散布的重复序列是造成大部分“拷贝数”或结构性等位基因变化的很大一部分，例如大删除，重复和外源DNA的插入，这比以前假定的更为普遍，并且比小突变更可能与表型差异和遗传疾病相关。