Development and Maintenance of RepeatMasker

RepeatMasker的开发与维护

• 批准号: 8847758
• 负责人: Arian Fredericus Anthonius Smit
• 金额: $ 44.61万
• 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 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8847758
• 关键词: Address; Animals; Back; Benchmarking; Bioinformatics; Biology; Brain; Collaborations; Communities; Complex; Computer software; Consensus; Consensus Sequence; DNA Transposable Elements; Data Quality; Databases; Detection; Development; Development Plans; Evolution; Eye; Family; Future; Genome; Genomics; Grant; Health; Hereditary Disease; Housing; Human; Human Genome; Institutes; Junk DNA; Knowledge; Libraries; Light; Maintenance; Medical; Methods; Modeling; Mutation; Phylogeny; Play; Pluripotent Stem Cells; Process; Publications; Research; Research Personnel; Role; Running; Scientist; Seeds; Sensitivity and Specificity; Sequence Analysis; Shapes; Source Code; Specificity; Speed; Staging; Study models; Time; Variant; Vertebrates; Work; base; comparative; computerized tools; dark matter; design; feeding; genome analysis; genome sequencing; genome-wide; improved; innovation; markov model; neurodevelopment; programs; reconstruction; research and development; software development; success; tool; tumorigenesis; vertebrate genome

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, RepeatModeler, a program designed to derive RepeatMasker-grade databases of IR consensus sequences, and related software. The source code for these tools is freely available to the public. We have recently co-created a database of profile Hidden Markov Models, called Dfam, for repeat families found in the human genome. RepeatMasker can use this database and we have found dramatically increased sensitivity over previous results. Our research and development plans include the following: a) We propose several ways in which sensitivity of detection can still be improved, including the creation of better profiles and exploiting our false positive and false negative benchmarks. b) To prepare for the onslaught of the 10,000 vertebrate genome project, we propose significant speed up strategies for both library creation and repeat analysis, and plan to improve repeat analysis for NextGen generated genomes. c) Dfam is meant to eventually comprise repeats for "all" genomes In collaboration with our colleagues at the Howard Hughes Medical Institute who house Dfam, we aim to develop tools to simplify and enhance submission and curation of entries. d) We plan to optimize our method of superimposing the RepeatMasker annotation of reconstructed ancestral genomes on extant genomes. We also propose several strategies involving IRs that could improve the construction of ancestral genomes.

描述（由申请人提供）： 大多数真核生物基因组都包含大量散在重复序列（IR），它们是大多数自私扩增的转座元件的残余物。转座元件对基因组具有异常广泛的诱变作用，而IR的识别提供了关于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。这笔赠款将继续支持 RepeatMasker 的维护和进一步开发，RepeatMasker 是一种计算工具，已成为 IR 识别和表征的事实上的标准；RepeatModeler 是一个旨在派生 IR 一致序列的 RepeatMasker 级数据库的程序，以及相关软件。这些工具的源代码免费向公众开放。我们最近共同创建了一个名为 Dfam 的隐马尔可夫模型数据库，用于在人类基因组中发现的重复家族。 RepeatMasker 可以使用该数据库，我们发现与之前的结果相比，灵敏度显着提高。我们的研究和开发计划包括以下内容：a）我们提出了几种仍然可以提高检测灵敏度的方法，包括创建更好的配置文件以及利用我们的误报和误报基准。 b) 为了准备迎接 10,000 个脊椎动物基因组计划的冲击，我们提出了文库创建和重复分析的显着加速策略，并计划改进 NextGen 生成的基因组的重复分析。 c) Dfam 旨在最终包含“所有”基因组的重复序列 通过与 Dfam 所在地霍华德休斯医学研究所的同事合作，我们的目标是开发工具来简化和增强条目的提交和管理。 d) 我们计划优化将重建祖先基因组的 RepeatMasker 注释叠加到现存基因组上的方法。我们还提出了几种涉及 IR 的策略，可以改善祖先基因组的构建。