Alternative splicing is a major source of regulatory and functional diversity in higher eukaryotes. In humans, over 90% of multi-exon genes are alternatively spliced, and aberrant alternative splicing causes a broad range of diseases. We have developed computational tools for global analysis of splicing regulatory networks using high-density splicing microarray and ultra-deep transcriptome sequencing. We have used these technologies to dissect an extensive epithelial-specific splicing regulatory network with critical roles in embryonic development and cancer metastasis. In a separate study, by combining high-throughput approaches with detailed molecular investigations, we have shown that humans and closely related species display widespread differences in exon usage and splicing patterns. These findings shed light on how evolutionary innovations in RNA processing expand the functional and regulatory repertoire of eukaryotic genomes.
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