Beyond comparisons of means: understanding changes in gene expression at the single-cell level

Genome Biol. 2016 Apr 15:17:70. doi: 10.1186/s13059-016-0930-3.

Abstract

Traditional differential expression tools are limited to detecting changes in overall expression, and fail to uncover the rich information provided by single-cell level data sets. We present a Bayesian hierarchical model that builds upon BASiCS to study changes that lie beyond comparisons of means, incorporating built-in normalization and quantifying technical artifacts by borrowing information from spike-in genes. Using a probabilistic approach, we highlight genes undergoing changes in cell-to-cell heterogeneity but whose overall expression remains unchanged. Control experiments validate our method's performance and a case study suggests that novel biological insights can be revealed. Our method is implemented in R and available at https://github.com/catavallejos/BASiCS.

Keywords: Cellular heterogeneity; Differential expression; Single-cell RNA-seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bayes Theorem
  • Gene Expression Profiling / methods*
  • Genetic Heterogeneity
  • Humans
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Sequence Analysis, RNA / methods*
  • Single-Cell Analysis / methods*
  • Web Browser