NEW WORD BASED METHODS FOR DNA SEQUENCE ASSEMBLY

基于新单词的 DNA 序列组装方法

• 批准号: 2536784
• 负责人: MAXIMILLIAN A KARLOVITZ
• 金额: $ 10万
• 依托单位: DANIEL H. WAGNER ASSOCIATES, INC.
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2536784
• 关键词: artificial intelligence; computer assisted sequence analysis; computer program /software; computer system design /evaluation; method development; nucleic acid sequence

The growing use of DNA sequence data in research, databases, diagnostic and therapeutic biotechnology, and even litigation dramatically increases the need to improve the quality of data being used. This proposal addresses the problem of assembling a large set of sequenced DNA fragments into a finished consensus. In order for a sequencing project to produce high quality finished sequence data, the assembly of sequence fragments must be correct and accurate both in its large scale structure and in the fine scale detail of the alignment of individual base calls. We propose to investigate new algorithms for consensus estimation and assembly of DNA sequence fragments. Recent novel word- based approaches to consensus estimation offer promise as a method for de novo assembly and for exploring alternative assemblies on the large scale. This will be especially important when sequences contain large exact or approximate repeats. We propose to develop several main enhancements to these algorithms. In particular, we will develop a global optimization algorithm for determining consensus sequences, replacing current locally optimizing methods. Also, we propose to develop algorithms allowing alternative alignments in regions of ambiguity. This approach will allow us to assess alignment accuracy at both the large and fine scale level. PROPOSED COMMERCIAL APPLICATION Accurate assemblies are at the heart of many sequencing projects central to biopharmaceutical, agricultural, and basic research as well as to the Human Genome Project. The proposed advances will provide the potential for simultaneously increasing reliability and automation in a bioinformatics software market totaling about 100 million dollars per year.

在研究，数据库，诊断中，DNA序列数据的使用日益增长 和治疗性生物技术，甚至诉讼 增加了提高所使用数据质量的需求。 这 提案解决了组装​​大量测序的问题 DNA片段成最终的共识。为了进行测序 项目生成高质量的成品数据，组装 序列片段必须大规模正确且准确 结构以及个人对齐方式的细节 基本电话。我们建议研究共识的新算法 DNA序列片段的估计和组装。 最近的小说单词 - 基于共识估计的方法提供了承诺作为一种方法 从头大会和探索大型组装 规模。 当序列包含大的序列时，这将特别重要 精确或近似重复。 我们建议开发几个主要 这些算法的增强。 特别是，我们将发展一个 用于确定共识序列的全局优化算法， 替换当前当前优化方法。 另外，我们建议 开发算法，允许在 歧义。 这种方法将使我们能够评估一致性的准确性 大型和精细的水平。 拟议的商业应用 准确的组件是许多测序项目中心的核心 生物制药，农业和基础研究以及 人类基因组项目。 拟议的进步将提供潜力 同时提高可靠性和自动化 生物信息学软件市场总计约1亿美元 年。