title: Beyond comparisons of means: understanding changes in gene expression at the single-cell level.
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.
authors.affiliation: MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, UK. catalina.vallejos@mrc-bsu.cam.ac.uk.|EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK. catalina.vallejos@mrc-bsu.cam.ac.uk.
authors.forename: Catalina A
authors.initials: CA
authors.lastname: Vallejos
authors.affiliation: MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, UK. sylvia.richardson@mrc-bsu.cam.ac.uk.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Richardson
authors.affiliation: EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK. marioni@ebi.ac.uk.|Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK. marioni@ebi.ac.uk.
authors.forename: John C
authors.initials: JC
authors.lastname: Marioni
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D020869:Gene Expression Profiling / Q000379:methods*; D018740:Genetic Heterogeneity; D006801:Humans; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology; D017423:Sequence Analysis, RNA / Q000379:methods*; D059010:Single-Cell Analysis / Q000379:methods*; D064878:Web Browser
keywords: Cellular heterogeneity; Differential expression; Single-cell RNA-seq