CAREER: Computational Tools for Interpreting Genomes

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CAREER奖，用于支持加州大学欧文分校计算机科学系谢晓辉博士的研究。谢博士是二年级的终身助理教授。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要。比较基因组学是发现基因组中功能元素的一种有效方法。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水平的保守性从周围序列中脱颖而出。本研究正在开发新的统计和计算工具，用于比较基因组分析，并通过从这些功能元件的偏倚核苷酸取代模式中模拟这些功能元件的进化约束来发现基因组中的功能元件。比较基因组学常用方法的一个假设是，功能序列的进化速度比中性序列慢，并且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改变而不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素时可能能力较弱。其次，基于速率的方法仅确定序列是否保守，但不提供有关保守序列每个核苷酸编码的特定约束的信息。这项工作是通过开发直接从序列比对中推断这些模式的算法，研究不同核苷酸之间的替代模式是否在进化时间中表现出偏见。作为他职业规划的一部分，谢博士正在开发两门新的生物信息学课程，一门本科和另一门研究生课程，以及两门额外的计算生物学课程。这项研究包括来自加州大学洛杉矶分校少数民族科学项目和加州州立数学与科学暑期学校（COSMOS）项目的学生，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公众可访问的网络服务http://www.ics.uci.edu/~xhx/免费提供。

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/.