Discovery and quantification of transcript variants with SQUARETM mRNA-Seq

The vast majority of genes are alternatively spliced and produce a variety of mature transcripts. These transcript variants often encode proteins with different structures and functions, and changes in the expression of variants from the same gene can lead to profound biological effects (reviewed in 1). Various transcriptional events, including splicing from alternative 5’ or 3’ splice-sites, exon skipping, intron retention and the usage of different promoters or polyadenylation signals lead to a staggering number of potential transcript variants for each gene. Current next generation sequencing (NGS) technologies fail to adequately address this diversity; most RNA-seq experiments result in the cumulative quantification of all variants of a gene, without regard for the different structures and abundances of each transcript.