title: Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells.
abstract: Recent technical developments have enabled the transcriptomes of hundreds of cells to be assayed in an unbiased manner, opening up the possibility that new subpopulations of cells can be found. However, the effects of potential confounding factors, such as the cell cycle, on the heterogeneity of gene expression and therefore on the ability to robustly identify subpopulations remain unclear. We present and validate a computational approach that uses latent variable models to account for such hidden factors. We show that our single-cell latent variable model (scLVM) allows the identification of otherwise undetectable subpopulations of cells that correspond to different stages during the differentiation of naive T cells into T helper 2 cells. Our approach can be used not only to identify cellular subpopulations but also to tease apart different sources of gene expression heterogeneity in single-cell transcriptomes.
authors.affiliation: 1] Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany. [2] European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Florian
authors.initials: F
authors.lastname: Buettner
authors.affiliation: 1] European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. [2] Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Kedar N
authors.initials: KN
authors.lastname: Natarajan
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: F Paolo
authors.initials: FP
authors.lastname: Casale
authors.affiliation: 1] European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. [2] Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Proserpio
authors.affiliation: 1] European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. [2] Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Antonio
authors.initials: A
authors.lastname: Scialdone
authors.affiliation: 1] Helmholtz Zentrum München-German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany. [2] Department of Mathematics, Technische Universität München, Munich, Germany.
authors.forename: Fabian J
authors.identifier: 0000000224191943
authors.initials: FJ
authors.lastname: Theis
authors.affiliation: 1] European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. [2] Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Teichmann
authors.affiliation: 1] European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. [2] Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Marioni
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
authors.forename: Oliver
authors.identifier: 0000000288187193
authors.initials: O
authors.lastname: Stegle
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics*; D019295:Computational Biology; D018507:Gene Expression Regulation, Developmental; D018740:Genetic Heterogeneity; D051379:Mice; D008962:Models, Theoretical; D000066450:Mouse Embryonic Stem Cells; D012313:RNA / Q000235:genetics; D017423:Sequence Analysis, RNA; D059010:Single-Cell Analysis; D018418:Th2 Cells / Q000166:cytology*; D059467:Transcriptome / Q000235:genetics
chemical_list: D012313:RNA