Alternative splicing: Human disease and quantitative analysis from high-throughput sequencing

Alternative splicing contributes to the majority of protein diversity in higher eukaryotes by allowing one gene to generate multiple distinct protein isoforms. It adds another regulation layer of gene expression. Up to 95% of human multi-exon genes undergo alternative splicing to encode proteins with different functions. Moreover, around 15% of human hereditary diseases and cancers are associated with alternative splicing. Regulation of alternative splicing is attributed to a set of delicate machineries interacting with each other in aid of important biological processes such as cell development and differentiation. Given the importance of alternative splicing events, their accurate mapping and quantification are paramount for downstream analysis, especially for associating disease with alternative splicing. However, deriving accurate isoform expression from high-throughput RNA-seq data remains a challenging task. In this mini-review, we aim to illustrate I) mechanisms and regulation of alternative splicing, II) alternative splicing associated human disease, III) computational tools for the quantification of isoforms and alternative splicing from RNA-seq.