Linnorm: improved statistical analysis for single cell RNA-seq expression data

被引:76
作者
Yip, Shun H. [1 ,2 ,3 ,4 ]
Wang, Panwen [2 ,3 ]
Kocher, Jean-Pierre A. [2 ,3 ]
Sham, Pak Chung [1 ,5 ,6 ]
Wang, Junwen [2 ,3 ,7 ]
机构
[1] Univ Hong Kong, LKS Fac Med, Ctr Genom Sci, Hong Kong, Hong Kong, Peoples R China
[2] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ 85259 USA
[3] Mayo Clin, Ctr Individualized Med, Scottsdale, AZ 85259 USA
[4] Univ Hong Kong, LKS Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China
[5] Univ Hong Kong, LKS Fac Med, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China
[6] Univ Hong Kong, LKS Fac Med, State Key Lab Cognit & Brain Sci, Hong Kong, Hong Kong, Peoples R China
[7] Arizona State Univ, Dept Biomed Informat, Scottsdale, AZ 85259 USA
关键词
GENE-EXPRESSION; TRANSCRIPTOME;
D O I
10.1093/nar/gkx828
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy.
引用
收藏
页数:12
相关论文
共 32 条
[1]   SCnorm: robust normalization of single-cell RNA-seq data [J].
Bacher, Rhonda ;
Chu, Li-Fang ;
Leng, Ning ;
Gasch, Audrey P. ;
Thomson, James A. ;
Stewart, Ron M. ;
Newton, Michael ;
Kendziorski, Christina .
NATURE METHODS, 2017, 14 (06) :584-+
[2]   Design and computational analysis of single-cell RNA-sequencing experiments [J].
Bacher, Rhonda ;
Kendziorski, Christina .
GENOME BIOLOGY, 2016, 17
[3]   Trimmomatic: a flexible trimmer for Illumina sequence data [J].
Bolger, Anthony M. ;
Lohse, Marc ;
Usadel, Bjoern .
BIOINFORMATICS, 2014, 30 (15) :2114-2120
[4]   Near-optimal probabilistic RNA-seq quantification [J].
Bray, Nicolas L. ;
Pimentel, Harold ;
Melsted, Pall ;
Pachter, Lior .
NATURE BIOTECHNOLOGY, 2016, 34 (05) :525-527
[5]  
Brennecke P, 2013, NAT METHODS, V10, P1093, DOI [10.1038/nmeth.2645, 10.1038/NMETH.2645]
[6]   Single-Cell RNA-Seq Reveals Dynamic, Random Monoallelic Gene Expression in Mammalian Cells [J].
Deng, Qiaolin ;
Ramskold, Daniel ;
Reinius, Bjorn ;
Sandberg, Rickard .
SCIENCE, 2014, 343 (6167) :193-196
[7]   Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq [J].
Islam, Saiful ;
Kjallquist, Una ;
Moliner, Annalena ;
Zajac, Pawel ;
Fan, Jian-Bing ;
Lonnerberg, Peter ;
Linnarsson, Sten .
GENOME RESEARCH, 2011, 21 (07) :1160-1167
[8]   SAMstrt: statistical test for differential expression in single-cell transcriptome with spike-in normalization [J].
Katayama, Shintaro ;
Tohonen, Virpi ;
Linnarsson, Sten ;
Kere, Juha .
BIOINFORMATICS, 2013, 29 (22) :2943-2945
[9]   Droplet Barcoding for Single-Cell Transcriptomics Applied to Embryonic Stem Cells [J].
Klein, Allon M. ;
Mazutis, Linas ;
Akartuna, Ilke ;
Tallapragada, Naren ;
Veres, Adrian ;
Li, Victor ;
Peshkin, Leonid ;
Weitz, David A. ;
Kirschner, Marc W. .
CELL, 2015, 161 (05) :1187-1201
[10]   voom: precision weights unlock linear model analysis tools for RNA-seq read counts [J].
Law, Charity W. ;
Chen, Yunshun ;
Shi, Wei ;
Smyth, Gordon K. .
GENOME BIOLOGY, 2014, 15 (02)