CAREER: Computational Tools for Interpreting Genomes

职业：解释基因组的计算工具

• 批准号: 0846218
• 负责人: Xiaohui Xie
• 金额: $ 75.2万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0846218&HistoricalAwards=false
• 关键词: CAREER; Computational; Tools; Interpreting; Genomes

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).This is a CAREER award to support the research of Dr. Xiaohui Xie in the Department of Computer Science at UC-Irvine. Dr. Xie is a second year, tenure-track Assistant Professor. Identification of all functional elements encoded in genomes is a fundamental need in genomic research. A powerful approach for discovering functional elements in the genome is through comparative genomics. Functional sequences are often under strong selection pressure to remain conserved so they can stand out from the surrounding sequence by virtue of greater levels of conservation. This research is developing novel statistical and computational tools for comparative genome analysis and for discovering functional elements in genomes by modeling the evolutionary constraints of these functional elements from their biased nucleotide substitution patterns. An assumption underlying more common methods for comparative genomics is that the functional sequences are evolving at a slower rate than neutral sequences, and are modeled as having shorter evolutionary distance between species than neutral sequences. In fact, many functional nucleotides can change between certain nucleotides without affecting the function they encode so that mutation-based approaches may have less power for detecting less obvious functional elements. Secondly, the rate-based methods only determine whether a sequence is conserved or not, but do not provide information regarding the specific constraints encoded at each nucleotide of the conserved sequence. This work is examining whether substitution patterns between different nucleotides show a bias over evolutionary time through the development of algorithms to infer these patterns directly from sequence alignments. As part of his CAREER plan, Dr. Xie is developing an extensive curriculum of two new bioinformatics courses, one undergraduate and the other graduate and two additional courses in computational biology. The research includes the involvement of students from the minority science program at UCI and from the California State Summer School for Mathematics and Science (COSMOS) program, a high school student summer school program. The results from this research will provide new scientific resources because the computational tools and results will be freely available through publicly-accessible web services at http://www.ics.uci.edu/~xhx/.

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。这是一个职业奖，以支持加州大学欧文分校计算机科学系谢晓晖博士的研究。谢博士是第二年，终身助理教授。鉴定基因组中编码的所有功能元件是基因组研究的基本需求。比较基因组学是发现基因组中功能元件的一个强有力的方法。功能序列通常在强大的选择压力下保持保守，因此它们可以凭借更高的保守水平从周围的序列中脱颖而出。这项研究正在开发新的统计和计算工具，用于比较基因组分析和发现基因组中的功能元件，通过模拟这些功能元件的进化限制，从他们的偏见核苷酸取代模式。比较基因组学的一个假设是功能序列的进化速度比中性序列慢，并且被建模为物种之间的进化距离比中性序列短。事实上，许多功能性核苷酸可以在某些核苷酸之间发生变化，而不会影响它们编码的功能，因此基于突变的方法在检测不太明显的功能元件时可能具有较低的能力。其次，基于速率的方法仅确定序列是否保守，但不提供关于在保守序列的每个核苷酸处编码的特定约束的信息。这项工作正在研究不同核苷酸之间的取代模式是否显示出进化时间的偏差，通过开发算法来直接从序列比对中推断这些模式。作为他的职业生涯计划的一部分，谢博士正在开发两个新的生物信息学课程，一个本科生和另一个研究生和两个计算生物学课程的广泛课程。这项研究包括来自UCI少数民族科学项目和加州州立数学和科学暑期学校（COSMOS）项目的学生的参与，这是一个高中生暑期学校项目。这项研究的结果将提供新的科学资源，因为计算工具和结果将通过http://www.ics.uci.edu/~xhx/的公共访问网络服务免费提供。