Wen Wei Xiong, Mead Adam J, Thongjuea Supat
MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
MRC WIMM Centre for Computational Biology, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
Comput Struct Biotechnol J. 2020 Feb 5;18:332-343. doi: 10.1016/j.csbj.2020.01.009. eCollection 2020.
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.
RNA的可变剪接产生异构体多样性，从而产生维持细胞功能和特性所必需的不同蛋白质。下一代转录组测序（主要使用批量RNA测序）彻底改变了可变剪接的发现，该技术揭示了稳态和应激条件下正常细胞的RNA剪接和错误剪接。单细胞RNA测序研究主要集中在基因水平的表达分析，并揭示了不同细胞类型之间可区分的基因表达特征。单细胞可变剪接是一个新兴的研究领域，有望揭示批量和基因水平分析所无法察觉的转录组动态。在这篇综述中，我们将讨论单细胞可变剪接分析的技术进展、单细胞中异构体检测和定量的计算策略、单细胞可变剪接分析的当前应用及其对个性化医疗未来可能的贡献。
