title: MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data.
abstract: Single-cell transcriptomics reveals gene expression heterogeneity but suffers from stochastic dropout and characteristic bimodal expression distributions in which expression is either strongly non-zero or non-detectable. We propose a two-part, generalized linear model for such bimodal data that parameterizes both of these features. We argue that the cellular detection rate, the fraction of genes expressed in a cell, should be adjusted for as a source of nuisance variation. Our model provides gene set enrichment analysis tailored to single-cell data. It provides insights into how networks of co-expressed genes evolve across an experimental treatment. MAST is available at https://github.com/RGLab/MAST .
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. gfinak@fredhutch.org.
authors.forename: Greg
authors.initials: G
authors.lastname: Finak
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. amcdavid@fredhutch.org.
authors.forename: Andrew
authors.initials: A
authors.lastname: McDavid
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. myajima@fredhutch.org.
authors.forename: Masanao
authors.initials: M
authors.lastname: Yajima
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. jdeng@fredhutch.org.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Deng
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA, 98101, USA. vgersuk@benaroyaresearch.org.
authors.forename: Vivian
authors.initials: V
authors.lastname: Gersuk
authors.affiliation: Institute for Medical Engineering & Science, MIT, Boston, MA, 01239-4307, USA. shalek@mit.edu.|Department of Chemistry, MIT, Boston, MA, 01239-4307, USA. shalek@mit.edu.|Ragon Institute of MGH, MIT, & Harvard, Boston, MA, 02139-3583, USA. shalek@mit.edu.|Broad Institute of MIT & Harvard, Boston, MA, 01242, USA. shalek@mit.edu.
authors.forename: Alex K
authors.initials: AK
authors.lastname: Shalek
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. cslichte@fredhutch.org.
authors.forename: Chloe K
authors.initials: CK
authors.lastname: Slichter
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. hwmiller@fredhutch.org.
authors.forename: Hannah W
authors.initials: HW
authors.lastname: Miller
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. jmcelrat@fredhutch.org.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. mprlic@fredhutch.org.
authors.forename: Martin
authors.initials: M
authors.lastname: Prlic
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, WA, 98101, USA. plinsley@benaroyaresearch.org.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Linsley
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. rgottard@fredhutch.org.|Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA. rgottard@fredhutch.org.
authors.forename: Raphael
authors.initials: R
authors.lastname: Gottardo
mesh_terms: D000818:Animals; D003627:Data Interpretation, Statistical; D003713:Dendritic Cells / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D014644:Genetic Variation; D006801:Humans; D016014:Linear Models; D051379:Mice; D017423:Sequence Analysis, RNA / Q000379:methods*; D059010:Single-Cell Analysis; D059467:Transcriptome