Computational methods for allele-specific expression in single cells

Trends Genet. 2024 Nov;40(11):939-949. doi: 10.1016/j.tig.2024.07.003. Epub 2024 Aug 10.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Alleles*
  • Allelic Imbalance / genetics
  • Animals
  • Computational Biology* / methods
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / genetics
  • Humans
  • Sequence Analysis, RNA* / methods
  • Single-Cell Analysis* / methods