Technological advances and computational approaches for alternative splicing analysis in single cells

Alternative splicing of RNAs generates isoform diversity, resulting in different proteins that are necessary for maintaining cellular function and identity. The discovery of alternative splicing has been revolutionized by next-generation transcriptomic sequencing mainly using bulk RNA-sequencing, which has unravelled RNA splicing and mis-splicing of normal cells under steady-state and stress conditions. Single-cell RNA-sequencing studies have focused on gene-level expression analysis and revealed gene expression signatures distinguishable between different cellular types. Single-cell alternative splicing is an emerging area of research with the promise to reveal transcriptomic dynamics invisible to bulk- and gene-level analysis. In this review, we will discuss the technological advances for single-cell alternative splicing analysis, computational strategies for isoform detection and quantitation in single cells, and current applications of single-cell alternative splicing analysis and its potential future contributions to personalized medicine.