Algorithms and Software for Molecular Sequence Exploration

生物分子序列的比对已成为现代分子生物学和生物技术研究的重要内容。这个项目将开发和测试探索DNA和蛋白质序列的算法技术，重点是较新的或较少分析的生物现象的技术。有几个集中的领域：根据最近获得的序列数据和对突变机制的积累了解，从根本上重新检查比对模型和参数的生物学基础；将参数比对方法扩展到应用于更广泛的序列分析问题；开发组织大量比对的方法，以便在不给研究人员带来负担的情况下提供替代比对；形成包含变异的重复亚串的概念，并利用精确重复研究中的深层定理；将蛋白质结构比对问题与位置理论的一系列有效技术联系起来。分子序列比对是人类基因组计划等获得各种基因组DNA全序列转录本的项目的必要补充。物种内和物种间的序列比较极大地加速了分子生物学和生物技术的许多任务。该项目的潜在影响将是开发更多基于生物学的比对模型，生产新的软件，以及使成熟的数学和计算技术适应分子生物学的问题。由于序列比较现在已经成为分子生物学以及商业生物技术和制药公司的许多方面的关键，改进的序列比较模型和软件可能会对识别疾病基因的方式、了解新识别的基因的功能以及识别新的候选药物分子靶标的方式产生重大影响。这项工作是由计算生物学活动(BIO)和计算理论计划(CEISE)资助的。

Comparison of bio-molecular sequences has become essential in modern molecular biology and biotechnology. This project will develop and test algorithmic techniques to explore DNA and protein sequences, with emphasis on techniques for newer or less analyzed biological phenomena. There are several areas of concentration: A fundamental re-examination of the biological basis for alignment models and parameters in light of the recently available sequence data and the accumulating understanding of mutation mechanisms; Expansion of parametric alignment methods to apply to a broader range of sequence analysis problems; Development of methods to organize a large set of alignments, in order to present alternative alignments without overwhelming the researcher; Formalizing notions of repeated substrings containing variations, and exploiting deep theorems from the study of exact repeats; Connecting the problem of protein structure alignment to a body of efficient techniques from Location Theory. Molecular sequence comparison is the essential complement of projects, such as the human genome project, that are obtaining the full DNA sequence transcript of various genomes. Comparison of sequences inside and across species has tremendously accelerated many tasks in molecular biology and biotechnology. The potential impact of this project will be in the development of more biologically based alignment models, in the production of novel software, and in the adaptation of mature mathematical and computational techniques to problems in molecular biology. Since sequence comparison has now become critical in molecular biology and in many aspects of commercial bio-technology and pharmaceutical companies, improved models and software for sequence comparison may have a significant impact on the way disease genes are identified, on the way newly identified genes are understood to function, and on the way new candidate molecular targets for medicines are identified. This work is funded by the Computational Biology Activity (BIO) and the program in the Theory of Computing (CISE).