CAREER: Computational Tools for Interpreting Genomes

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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/.