Welcome to the Xing Laboratory of RNA Genomics and Bioinformatics!
We are in the Department of Internal Medicine and Department of Biomedical Engineering at University of Iowa. We are also affliated with the Ph.D. programs in Genetics and Biosciences.
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.