Continued Improvements of Whole Genome Shotgun Assembly

全基因组鸟枪组装的持续改进

• 批准号: 7920507
• 负责人: JAMES A YORKE
• 金额: $ 7.13万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-05 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7920507
• 关键词: African; Award; Collaborations; Computer software; Data; Data Quality; Detection; Elephants; Evaluation; Genes; Genetic Structures; Genome; Goals; Government; Human Genome; Lead; Location; Measures; Methods; Nucleic Acid Regulatory Sequences; Output; Partner in relationship; Procedures; Process; Public Health; Reading; Repetitive Sequence; Research Personnel; Shotguns; Techniques; Time; Whole-Genome Shotgun Sequencing; Work; base; cost; experience; genome sequencing; improved; open source; programs; software development; statistics; tool; vector

DESCRIPTION (provided by applicant): Our goal is to develop a set of pre- and post-processing tools that are independent of the assembly software used and thus could be immediately implemented at all major sequencing/assembly centers. We will make our software and methods freely available, open source. Pre-processing: Specific Aim 1. Improving draft genome assemblies through better use of read data, (a) Vector Trimming: Improperly trimmed vector sequences often cause genome assemblies to break unnecessarily. We propose an improved vector trimming method that determines vector sequence automatically, (b) We propose to preprocess the read data to increase the amount of useable sequence on the 3' ends of the reads using overlap-based error correction followed by overlap-based trimming. We propose to use low quality bases on the 3' ends of the reads to help resolve repetitive regions. This procedure would be used to further improve UMD Overlapper. (c) We propose to use our read extension and error correction routines to create better assemblies of genomes sequenced at low. Post-processing:We propose to develop a set of assembler-independent techniques that can be used at any sequencing/assembly center or in the framework of any sequencing consortium. Specific Aim 2. Assembly evaluation software. We have developed a Compression/Expansion (CE) statistic that allows us to detect misassembled regions in the draft assemblies. We also developed software that uses shooting method to determine which inserts lie in easy to assemble (not necessarily unique) regions of the genome and exactly measure their size. We propose to develop integrated assembly evaluation/misassembly detection software that uses statistics based on read and mate pair placements and data obtained from the shooting methods to detect problems in draft assemblies. Specific Aim 3. Assembly reconciliation. We propose to create software that enhances a given draft assembly using alternate draft assemblies of the same genome created from the same read data with different assembly programs, or with the same assembly program using different parameters. The U.S. government spends hundreds of millions of dollars on whole genome shotgun sequencing. We believe that if the goals of this project are achieved, significantly better and cheaper genomes will be produced. The cost of using our techniques will be negligible compared to the cost of generating reads. Our approach may find more genes and regulatory regions and lead to a better understanding of the genetic structure of the various genomes. The ultimate goal of this project is to improve public health by better understanding the human genome and the genomes of other species.

描述（由申请人提供）：我们的目标是开发一组独立于所使用的组装软件的预处理和后处理工具，因此可以在所有主要的测序/组装中心立即实现。我们将免费提供我们的软件和方法，开源。预处理：特定目的1。通过更好地使用读取数据来改善基因组组装草案，（a）矢量修剪：不当修剪的矢量序列通常会导致基因组组件不必要地破裂。我们提出了一种改进的矢量修剪方法，该方法可以自动确定向量序列，（b）我们建议使用基于重叠的误差校正，然后基于重叠的修剪来预处读取数据，以增加读取数据的3'端上的可用序列量。我们建议在读取的3'末端使用低质量基础，以帮助解决重复区域。此过程将用于进一步改善UMD重叠。 （c）我们建议使用我们的读取扩展和误差校正例程，以创建以下测序的基因组的更好组装。后处理：我们建议开发一组无独立的技术，这些技术可在任何测序/组装中心或任何测序联盟的框架中使用。特定目标2。组装评估软件。我们已经开发了一个压缩/扩展（CE）统计量，该统计量使我们能够检测组装草案中的错误组装区域。我们还开发了使用拍摄方法来确定哪些插入物的软件，位于基因组的易于组装（不一定是独特的）区域并准确衡量其大小。我们建议开发集成的组装评估/误配检测软件，该软件使用基于阅读和配对的统计数据以及从拍摄方法获得的数据来检测草案组件中的问题。特定目标3。集会对帐。我们建议创建软件，以使用具有不同的组装程序的相同读取数据或使用不同参数的相同读取数据创建的相同基因组的替代草稿组件来增强给定的草稿组件。美国政府在整个基因组shot弹枪测序上花费了数亿美元。我们认为，如果实现了该项目的目标，将产生更好，更便宜的基因组。与生成读取的成本相比，使用我们的技术的成本可以忽略不计。我们的方法可能会发现更多的基因和调节区域，并可以更好地理解各种基因组的遗传结构。该项目的最终目标是通过更好地了解人类基因组和其他物种的基因组来改善公共卫生。