Department of Internal Medicine
Bioinformatics and Computational Biology Faculty
Yi Xing, Ph.D.
Departments of Internal Medicine and Biomedical Engineering
Current Research Topics:
Our laboratory uses genomic, computational and molecular approaches to study gene expression and RNA processing in mammalian genomes. We develop computational and statistical tools for exon-level analysis of mammalian transcriptomes using high-density exon microarray and ultra-deep RNA-sequencing data. We conduct computational and experimental research to elucidate the molecular mechanism and regulatory impact of evolutionary changes in gene expression and RNA processing. We are also studying the role of alternative splicing and microRNAs in human diseases.
(1) Pre-mRNA splicing and alternative splicing
Alternative splicing is a major source of transcript and protein diversity in higher eukaryotes. During the splicing of precursor mRNAs, alternative choices of exons and splice sites can produce different mRNA and protein isoforms from a single gene. In the last decade, genomic data indicate that pre-mRNA alternative splicing is widespread in human and many other genomes. This has fascinating implications for the understanding of gene regulation and many human diseases. We develop bioinformatic tools to discover novel alternative splicing events from sequence and microarray data. We use these data to study pre-mRNA alternative splicing at functional, regulatory and evolutionary levels. We are also interested in the discovery and characterization of disease mutations that disrupt pre-mRNA splicing.
(2) Bioinformatic tool for exon-level analysis of mammalian transcriptomes.
For a long time, studies of alternative splicing were limited by the lack of high-throughput tools for global profiling of alternatively spliced transcripts. This situation is changing with the development of new transcriptome profiling technologies for splicing analysis. For example, RNA-seq (based on Illumina Solexa sequencing) is emerging as a powerful technology for exon-level expression analysis. By mapping millions of RNA-seq reads to individual transcripts and exons, one can estimate the overall abundance of the mRNA transcripts as well as the splicing levels of individual exons. My laboratory is currently developing computational tools for global analysis of splicing using public and in-house RNA-seq data. We are also developing statistical tools for a next-generation exon array, which has a much higher probe density per exon and also includes multiple probes for splice junctions.
(3) Comparative genomics
Our laboratory has a broad interest in comparative and evolutionary genomics. We study genome evolution using combined genomic, bioinformatic and experimental approaches. We are particularly interested in the evolutionary origin and regulatory impact of species-specific coding and non-coding RNA sequences.
(4) Disease-specific perturbation of splicing regulation
Aberrant alternative splicing is a major cause of human diseases. Defects in global regulators of alternative splicing have been implicated in cancers and a variety of genetic disorders. We are developing methods to construct global splicing regulatory networks from heterogeneous genome, transcriptome and protein-RNA interaction data. In collaboration with clinical colleagues, we are combining genomic, computational and experimental tools to delineate disease-specific perturbation of splicing regulatory networks. Currently, we focus on neurological diseases and muscular dystrophy.
Honors, Awards, and Organizations
- Basil O’Connor Starter Scholar Research Award, March of Dimes Foundation (2010-2012)
- Junior Faculty Grant, Edward Mallinckrodt Jr. Foundation (2009)
- 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
Links of Interest
- Warzecha CC., Jiang P., Amirikian, K., Dittmar, KA., Lu, H., Shen, S., Guo, W., Xing Y., Carstens RP. (2010) An ESRP-regulated splicing programme is abrogated during the epithelial-mesenchymal transition. EMBO J, advance access.
- Lin L.*, Shen S.*, Jiang P., Sato S., Davidson BL., Xing Y. (2010) Evolution of alternative splicing in primate brain transcriptomes. Human Molecular Genetics, 19:2958-2973 (*joint first authors).
- Shen S., Warzecha CC., Carstens RP., Xing Y. (2010) MADS+: discovery of differential splicing events from Affymetrix exon junction array data. Bioinformatics, 26:268-269.
- Lin L., Jiang P., Shen S., Sato S., Davidson BL., Xing Y. (2009) Large-scale analysis of exonized mammalian-wide interspersed repeats (MIRs) in primate genomes. Human Molecular Genetics. 18: 2204-2214
- Lin, L., Shen, S., Tye, A., Cai, JJ., Jiang, P., Davidson, BL., Xing, Y. (2008) Diverse splicing patterns of exonized Alu elements in human tissues. PLoS Genetics. 4(10):e1000225.
- 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).
- 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., 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.
- Xing,Y., Resch,A.,Lee,C. (2004) The multiassembly problem: reconstructing multiple transcript isoforms from EST fragment mixtures. Genome Research. 14(3):426-4.