SAVER: Gene Expression Recovery for Single-cell RNA Sequencing

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2018 Jun 27

PMID 29941873

Citations 305

Authors

Mo Huang

Jingshu Wang

Eduardo Torre

Hannah Dueck

Sydney Shaffer

Roberto Bonasio

John I Murray

Arjun Raj

Mingyao Li

Nancy R Zhang

Affiliations

Soon will be listed here.

Abstract

In single-cell RNA sequencing (scRNA-seq) studies, only a small fraction of the transcripts present in each cell are sequenced. This leads to unreliable quantification of genes with low or moderate expression, which hinders downstream analysis. To address this challenge, we developed SAVER (single-cell analysis via expression recovery), an expression recovery method for unique molecule index (UMI)-based scRNA-seq data that borrows information across genes and cells to provide accurate expression estimates for all genes.

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References

Jiang L, Chen H, Pinello L, Yuan G . GiniClust: detecting rare cell types from single-cell gene expression data with Gini index. Genome Biol. 2016; 17(1):144. PMC: 4930624. DOI: 10.1186/s13059-016-1010-4. View

Friedman J, Hastie T, Tibshirani R . Regularization Paths for Generalized Linear Models via Coordinate Descent. J Stat Softw. 2010; 33(1):1-22. PMC: 2929880. View

Zeisel A, Munoz-Manchado A, Codeluppi S, Lonnerberg P, La Manno G, Jureus A . Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq. Science. 2015; 347(6226):1138-42. DOI: 10.1126/science.aaa1934. View

Padovan-Merhar O, Nair G, Biaesch A, Mayer A, Scarfone S, Foley S . Single mammalian cells compensate for differences in cellular volume and DNA copy number through independent global transcriptional mechanisms. Mol Cell. 2015; 58(2):339-52. PMC: 4402149. DOI: 10.1016/j.molcel.2015.03.005. View

Baron M, Veres A, Wolock S, Faust A, Gaujoux R, Vetere A . A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure. Cell Syst. 2016; 3(4):346-360.e4. PMC: 5228327. DOI: 10.1016/j.cels.2016.08.011. View

Li W, Li J . An accurate and robust imputation method scImpute for single-cell RNA-seq data. Nat Commun. 2018; 9(1):997. PMC: 5843666. DOI: 10.1038/s41467-018-03405-7. View

Wills Q, Livak K, Tipping A, Enver T, Goldson A, Sexton D . Single-cell gene expression analysis reveals genetic associations masked in whole-tissue experiments. Nat Biotechnol. 2013; 31(8):748-52. DOI: 10.1038/nbt.2642. View

Bacher R, Chu L, Leng N, Gasch A, Thomson J, Stewart R . SCnorm: robust normalization of single-cell RNA-seq data. Nat Methods. 2017; 14(6):584-586. PMC: 5473255. DOI: 10.1038/nmeth.4263. View

La Manno G, Gyllborg D, Codeluppi S, Nishimura K, Salto C, Zeisel A . Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells. Cell. 2016; 167(2):566-580.e19. PMC: 5055122. DOI: 10.1016/j.cell.2016.09.027. View

10.

Kharchenko P, Silberstein L, Scadden D . Bayesian approach to single-cell differential expression analysis. Nat Methods. 2014; 11(7):740-2. PMC: 4112276. DOI: 10.1038/nmeth.2967. View

11.

Hrvatin S, Hochbaum D, Nagy M, Cicconet M, Robertson K, Cheadle L . Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nat Neurosci. 2017; 21(1):120-129. PMC: 5742025. DOI: 10.1038/s41593-017-0029-5. View

12.

Pierson E, Yau C . ZIFA: Dimensionality reduction for zero-inflated single-cell gene expression analysis. Genome Biol. 2015; 16:241. PMC: 4630968. DOI: 10.1186/s13059-015-0805-z. View

13.

Svensson V, Natarajan K, Ly L, Miragaia R, Labalette C, Macaulay I . Power analysis of single-cell RNA-sequencing experiments. Nat Methods. 2017; 14(4):381-387. PMC: 5376499. DOI: 10.1038/nmeth.4220. View

14.

Lun A, McCarthy D, Marioni J . A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor. F1000Res. 2016; 5:2122. PMC: 5112579. DOI: 10.12688/f1000research.9501.2. View

15.

Lun A, Bach K, Marioni J . Pooling across cells to normalize single-cell RNA sequencing data with many zero counts. Genome Biol. 2016; 17:75. PMC: 4848819. DOI: 10.1186/s13059-016-0947-7. View

16.

Chen R, Wu X, Jiang L, Zhang Y . Single-Cell RNA-Seq Reveals Hypothalamic Cell Diversity. Cell Rep. 2017; 18(13):3227-3241. PMC: 5782816. DOI: 10.1016/j.celrep.2017.03.004. View

17.

Torre E, Dueck H, Shaffer S, Gospocic J, Gupte R, Bonasio R . Rare Cell Detection by Single-Cell RNA Sequencing as Guided by Single-Molecule RNA FISH. Cell Syst. 2018; 6(2):171-179.e5. PMC: 6078200. DOI: 10.1016/j.cels.2018.01.014. View

18.

Finak G, McDavid A, Yajima M, Deng J, Gersuk V, Shalek A . MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data. Genome Biol. 2015; 16:278. PMC: 4676162. DOI: 10.1186/s13059-015-0844-5. View

19.

Satija R, Farrell J, Gennert D, Schier A, Regev A . Spatial reconstruction of single-cell gene expression data. Nat Biotechnol. 2015; 33(5):495-502. PMC: 4430369. DOI: 10.1038/nbt.3192. View

20.

Raj A, Peskin C, Tranchina D, Vargas D, Tyagi S . Stochastic mRNA synthesis in mammalian cells. PLoS Biol. 2006; 4(10):e309. PMC: 1563489. DOI: 10.1371/journal.pbio.0040309. View