Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Trends Genet. 2024 Nov;40(11):939-949. doi: 10.1016/j.tig.2024.07.003. Epub 2024 Aug 10.
Allele-specific expression (ASE) is a powerful signal that can be used to investigate multiple molecular mechanisms, such as cis-regulatory effects and imprinting. Single-cell RNA-sequencing (scRNA-seq) enables ASE characterization at the resolution of individual cells. In this review, we highlight the computational methods for processing and analyzing single-cell ASE data. We first describe a bioinformatics pipeline to obtain ASE counts from raw reads synthesized from previous literature. We then discuss statistical methods for detecting allelic imbalance and its variability across conditions using scRNA-seq data. In addition, we describe other methods that use single-cell ASE to address specific biological questions. Finally, we discuss future directions and emphasize the need for an integrated, optimized bioinformatics pipeline, and further development of statistical methods for different technologies.
等位基因特异性表达 (ASE) 是一种强大的信号,可以用于研究多种分子机制,如顺式调控效应和印迹。单细胞 RNA 测序 (scRNA-seq) 能够以单个细胞的分辨率来描述 ASE 特征。在这篇综述中,我们重点介绍了用于处理和分析单细胞 ASE 数据的计算方法。我们首先描述了一个从之前文献中合成的原始读段中获取 ASE 计数的生物信息学流程。然后,我们讨论了使用 scRNA-seq 数据检测等位基因失衡及其在不同条件下变异性的统计方法。此外,我们还描述了其他利用单细胞 ASE 来解决特定生物学问题的方法。最后,我们讨论了未来的方向,并强调需要一个集成的、优化的生物信息学流程,以及针对不同技术的统计方法的进一步发展。