Department of Internal Medicine

Bioinformatics and Computational Biology Faculty

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Yi Xing, Ph.D.
Assistant Professor
Departments of Internal Medicine and Biomedical Engineering

Our group is interested in the regulation and evolution of gene expression, in particular at the RNA level. We also develop computational methods for the analysis and integration of high-throughput genomic data.  A major goal of our research is to understand particular biological systems and diseases using genomic and bioinformatic tools.  We are working closely with collaborators in the study of cancer, stem cell biology and neuroscience.
 
1) Pre-mRNA splicing and alternative splicing
Our laboratory is interested in the functional impact, regulatory mechanism and evolution of pre-mRNA splicing and alternative splicing. Pre-mRNA splicing is a crucial step in eukaryotic gene expression. Variations in pre-mRNA splicing (i.e. alternative splicing) can give rise to functionally distinct transcripts and protein products from a single gene. In the last decade, genomic data indicate that pre-mRNA alternative splicing is widespread in higher eukaryotes, with a profound impact on gene regulation and human diseases. We develop computational tools to discover novel alternative splicing events and infer their likely functional consequences. We use high-density oligonucleotide microarrays to identify alternative splicing events during development, cellular signaling events, as well as disease-associated aberrant splice variants. We are also interested in the discovery and characterization of disease mutations that disrupt pre-mRNA splicing.

2) Genome evolution
Our laboratory has a broad interest in comparative and evolutionary genomics. We are particularly interested in the evolution of mammalian gene expression, and the origin and regulatory impact of species-specific coding and non-coding RNA sequences.
 
3) Microarray analysis
We develop computational tools for microarray data analysis. We are currently working with Wing Wong lab at Stanford University on Affymetrix Exon Arrays. The Exon Array is a high-density expression microarray platform, with six million probes targeting all exons in a genome. It provides a genome-wide view of gene expression at exon resolution. Its design is drastically different from conventional 3’ expression microarrays, and requires a completely new set of analytic tools. We are developing statistical methods for gene-level and exon-level analyses of Exon Arrays.

Honors, Awards, and Organizations

• UCLA Dissertation Year Fellowship (2005-2006)
• UCLA MBI Amgen Dissertation Award
• Finalist, Walter M. Fitch Prize, Society for Molecular Biology and Evolution
• International Society for Computational Biology
• RNA Society
• Society for Molecular Biology and Evolution

Recent Publications

• Lin, L., Shen, S., Tye, A., Cai, J., Jiang, P., Davidson, BL., Xing, Y. (2008) Diverse splicing patterns of exonized Alu elements in human tissues. PLoS Genetics, Accepted.
• Xing, Y.*, Stoilov, P., Kapur, K., Han, A., Jiang, H., Shen, S., Black, DL., Wong, WH*. (2008) MADS: a New and Improved Method for Analysis of Differential Alternative Splicing by Exon-tiling Microarrays. RNA.14(8):1470-1479 (* joint corresponding authors).
• Chiao, E, Elezar, M, Xing, Y.,Xiong, A., Kmet, M., Millan, M., Glenn, J., Wong, WH., Baker, J. (2008) Isolation and Transcriptional Profiling of Purified Hepatic Cells Derived from Human Embryonic Stem Cells. Stem Cells, 26(8):2032-2041.
• Calarco, JA.*, Xing, Y.*, Caceres, M.*, Calarco, JP., Xiao, X., Pan, Q., Lee, C., Preuss, T. and Blencowe, B. (2007) Global analysis of alternative splicing differences between humans and chimpanzees. Genes and Development. 21:2963-2975. (* joint first authors).
• Xing, Y. *, Ouyang, Z., Kapur, K., Scott, MP., Wong, WH*. (2007) Assessing the conservation of mammalian gene expression using high-density Exon Arrays. Molecular Biology and Evolution. 24(6):1-3. (* joint corresponding authors).
• Lee , JA., Xing, Y., Nguyen, D., Xie, J., Lee, C., Black, DL. (2007) Depolarization and CaM Kinase IV Modulate NMDA Receptor Splicing through Two Essential RNA Elements. PLoS Biology. 5(2):e40.
• Xing, Y., Kapur, K., Wong, WH. (2006) Probe selection and expression index computation of Affymetrix Exon Arrays. PLoS ONE. 1(1):e88.
• Xing, Y., Lee, C. (2006) Alternative splicing and RNA selection pressure: evolutionary consequences for eukaryotic genomes. Nature Reviews Genetics. 7:499-509.
• Xing,Y.,Lee,C. (2005) Protein modularity of alternatively spliced exons is associated with tissue-specific regulation of alternative splicing. PLoS Genetics. 1(3):e34.
• Xing,Y.,Lee,C. (2005) Evidence of functional selection pressure for alternative splicing events that accelerate evolution of protein subsequences. Proc. Natl. Acad. Sci. U.S.A. 102:13526-13531.
• Xing,Y.,Lee,C. (2004) Negative selection pressure against premature protein truncation is reduced by alternative splicing and diploidy. Trends in Genetics. 20:472-5.
• Resch,A., Xing,Y., Modrek,B.,Gorlick,M., Riley,R., Lee, C. (2004) Assessing the impact of alternative splicing on domain interactions in the human proteome. Journal of Proteome Research. 3:76-83.
• Xing,Y., Resch,A.,Lee,C. (2004) The multiassembly problem: reconstructing multiple transcript isoforms from EST fragment mixtures. Genome Research. 14(3):426-4.

Links of Interest

• Dr. Xing's Laboratory
• University of Iowa College of Engineering

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