ZIFA: Dimensionality reduction for zero-inflated single-cell gene expression analysis

被引:409
作者
Pierson, Emma [1 ]
Yau, Christopher [1 ,2 ]
机构
[1] Univ Oxford, Dept Stat, Oxford OX1 3TG, England
[2] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
HETEROGENEITY;
D O I
10.1186/s13059-015-0805-z
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Single-cell RNA-seq data allows insight into normal cellular function and various disease states through molecular characterization of gene expression on the single cell level. Dimensionality reduction of such high-dimensional data sets is essential for visualization and analysis, but single-cell RNA-seq data are challenging for classical dimensionality-reduction methods because of the prevalence of dropout events, which lead to zero-inflated data. Here, we develop a dimensionality-reduction method, (Z)ero (I)nflated (F)actor (A)nalysis (ZIFA), which explicitly models the dropout characteristics, and show that it improves modeling accuracy on simulated and biological data sets.
引用
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页数:10
相关论文
共 17 条
[1]   Dissecting genomic diversity, one cell at a time [J].
Blainey, Paul C. ;
Quake, Stephen R. .
NATURE METHODS, 2014, 11 (01) :19-21
[2]   Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells [J].
Buettner, Florian ;
Natarajan, Kedar N. ;
Casale, F. Paolo ;
Proserpio, Valentina ;
Scialdone, Antonio ;
Theis, Fabian J. ;
Teichmann, Sarah A. ;
Marioni, John C. ;
Stegie, Oliver .
NATURE BIOTECHNOLOGY, 2015, 33 (02) :155-160
[3]  
Islam S, 2014, NAT METHODS, V11, P163, DOI [10.1038/NMETH.2772, 10.1038/nmeth.2772]
[4]  
Kharchenko PV, 2014, NAT METHODS, V11, P740, DOI [10.1038/nmeth.2967, 10.1038/NMETH.2967]
[5]   MULTIDIMENSIONAL-SCALING BY OPTIMIZING GOODNESS OF FIT TO A NONMETRIC HYPOTHESIS [J].
KRUSKAL, JB .
PSYCHOMETRIKA, 1964, 29 (01) :1-27
[6]  
Lawrence N, 2005, J MACH LEARN RES, V6, P1783
[7]   Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma [J].
Patel, Anoop P. ;
Tirosh, Itay ;
Trombetta, John J. ;
Shalek, Alex K. ;
Gillespie, Shawn M. ;
Wakimoto, Hiroaki ;
Cahill, Daniel P. ;
Nahed, Brian V. ;
Curry, William T. ;
Martuza, Robert L. ;
Louis, David N. ;
Rozenblatt-Rosen, Orit ;
Suva, Mario L. ;
Regev, Aviv ;
Bernstein, Bradley E. .
SCIENCE, 2014, 344 (6190) :1396-1401
[8]   Low-coverage single-cell mRNA sequencing reveals cellular heterogeneity and activated signaling pathways in developing cerebral cortex [J].
Pollen, Alex A. ;
Nowakowski, Tomasz J. ;
Shuga, Joe ;
Wang, Xiaohui ;
Leyrat, Anne A. ;
Lui, Jan H. ;
Li, Nianzhen ;
Szpankowski, Lukasz ;
Fowler, Brian ;
Chen, Peilin ;
Ramalingam, Naveen ;
Sun, Gang ;
Thu, Myo ;
Norris, Michael ;
Lebofsky, Ronald ;
Toppani, Dominique ;
Kemp, Darnell W., II ;
Wong, Michael ;
Clerkson, Barry ;
Jones, Brittnee N. ;
Wu, Shiquan ;
Knutsson, Lawrence ;
Alvarado, Beatriz ;
Wang, Jing ;
Weaver, Lesley S. ;
May, Andrew P. ;
Jones, Robert C. ;
Unger, Marc A. ;
Kriegstein, Arnold R. ;
West, Jay A. A. .
NATURE BIOTECHNOLOGY, 2014, 32 (10) :1053-+
[9]   Spatial reconstruction of single-cell gene expression data [J].
Satija, Rahul ;
Farrell, Jeffrey A. ;
Gennert, David ;
Schier, Alexander F. ;
Regev, Aviv .
NATURE BIOTECHNOLOGY, 2015, 33 (05) :495-U206
[10]   Single-cell RNA-seq reveals dynamic paracrine control of cellular variation [J].
Shalek, Alex K. ;
Satija, Rahul ;
Shuga, Joe ;
Trombetta, John J. ;
Gennert, Dave ;
Lu, Diana ;
Chen, Peilin ;
Gertner, Rona S. ;
Gaublomme, Jellert T. ;
Yosef, Nir ;
Schwartz, Schraga ;
Fowler, Brian ;
Weaver, Suzanne ;
Wang, Jing ;
Wang, Xiaohui ;
Ding, Ruihua ;
Raychowdhury, Raktima ;
Friedman, Nir ;
Hacohen, Nir ;
Park, Hongkun ;
May, Andrew P. ;
Regev, Aviv .
NATURE, 2014, 510 (7505) :363-+