Alignment Software for Second-Generation Sequencing

用于第二代测序的比对软件

• 批准号: 8068060
• 负责人: Steven L. Salzberg
• 金额: $ 70.77万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-06 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8068060
• 关键词: Alternative Splicing; Back; Base Sequence; Biology; Computer software; Computers; DNA; DNA Sequence; DNA Sequence Analysis; Data; Data Set; Development; Disease; Explosion; Gene Expression Profile; Gene Mutation; Generations; Genes; Genetic Variation; Genome; Hour; Human; Human Genetics; Human Genome; Introns; Journals; Length; Maintenance; Malignant Neoplasms; Maps; Medicine; Memory; Messenger RNA; Metric; Output; Paper; Protein Isoforms; Protocols documentation; RNA; RNA Sequences; RNA Splicing; Reading; Research; Research Personnel; Running; Site; Software Tools; Speed; Statistical Models; System; Technology; Time; Transcript; Update; Variant; Work; base; cell type; computerized tools; design; exome; falls; genome sequencing; high standard; human disease; improved; next generation; novel; open source; programs; research study; software systems; tool

DESCRIPTION (provided by applicant): The latest generation of DNA sequencing technology has spurred a tremendous increase in the use of sequencing to answer fundamental questions in biology and medicine. Whole-genome sequencing is being used to study cancer, to study common disease-causing variants in the human genome, and to create a better picture of human diversity. Sequencing of messenger RNA through the protocol known as RNA-seq has led to an explosion of projects to characterize the transcriptome of many cell types in many species. These sequencing-based studies generate enormous amounts of data, which in turn require sophisticated, efficient computational tools to align the DNA sequence back to a reference genome and to help interpret the results. Our group has developed a suite of software tools for alignment of DNA and RNA to a reference genome. These include Bowtie, a very fast short-read alignment program; TopHat, an alignment program that aligns spliced transcripts (mRNA) across introns; and Cufflinks, a program that assembles complete transcripts, including alternative splice variants, from the alignments that TopHat produces. Our tools have been designed to handle very large next-generation sequence data sets, reducing alignment times that took multiple CPU-days with previous tools to just minutes. They also have relatively modest memory requirements, allowing them to be run on a desktop computer. For these and other reasons, these programs have become the preferred tools for numerous research groups; the Bowtie program alone has already attracted a very large user base, with over 20,000 downloads since its initial release in 2008. In this proposal, we ask for support to maintain these open-source software programs, adapt them to continuously changing DNA sequencing technology, and add new features designed to improve the alignments and to assist investigators with their analyses. PUBLIC HEALTH RELEVANCE: Many biomedical researchers are now using large-scale DNA sequencing to study human disease and genetic mutations. The analysis of these new types of sequence data requires highly sophisticated software that can align billions of DNA fragments to the human genome and identify various types of genetic variations. This proposal will support a suite of software tools that will help researchers take advantage of the latest DNA sequencing technology and apply it to the study of human genetics.

描述（由申请人提供）：最新一代的DNA测序技术刺激了测序在回答生物学和医学基本问题方面的巨大增长。全基因组测序正被用于研究癌症，研究人类基因组中常见的致病变异，并更好地描绘人类多样性。通过被称为RNA-seq的协议对信使RNA进行测序，导致了许多项目的爆发，以表征许多物种中许多细胞类型的转录组。这些基于测序的研究产生了大量的数据，这反过来又需要复杂、高效的计算工具来将DNA序列与参考基因组对齐，并帮助解释结果。我们的团队开发了一套软件工具，用于将DNA和RNA与参考基因组进行比对。其中包括Bowtie，一个非常快速的短读对齐程序；TopHat是一种比对程序，用于比对内含子间的剪接转录物（mRNA）；以及Cufflinks，这是一个从TopHat产生的比对中组装完整转录本的程序，包括可选择的剪接变体。我们的工具设计用于处理非常大的下一代序列数据集，将以前的工具需要多个cpu天的校准时间缩短到几分钟。它们对内存的要求也相对较低，因此可以在台式电脑上运行。由于这些和其他原因，这些程序已成为许多研究小组的首选工具；Bowtie程序本身就已经吸引了庞大的用户群，自2008年首次发布以来，下载量已超过2万次。在本提案中，我们请求支持维护这些开源软件程序，使其适应不断变化的DNA测序技术，并添加旨在改进比对并协助调查人员进行分析的新功能。