From another direction, the accumulation of large databases of cDNA and expressed sequence tag (EST) sequences has enabled large-scale computational studies, which have assessed the scope of AS in the mammalian transcriptome [3,8,10,28]. Other computational studies have analyzed the tissue specificity of AS events and identified sets of exons and genes that exhibit tissue-biased expression [29,30]. However, a number of significant questions about tissue-specific alternative splicing have not yet been comprehensively addressed. Which tissues have the highest and lowest proportions of alternative splicing? Do tissues differ in their usage of different AS types, such as exon skipping, alternative 5' splice site choice or alternative 3' splice site choice? Which tissues are most distinct from other tissues in the spectrum of alternative mRNA isoforms they express? And to what extent do expression levels of known splicing factors explain AS patterns in different tissues?
