Fast, sensitive and accurate integration of single-cell data with Harmony

被引:3782
|
作者
Korsunsky, Ilya [1 ,2 ,3 ,4 ,5 ,6 ]
Millard, Nghia [1 ,2 ,3 ,4 ,6 ]
Fan, Jean [7 ]
Slowikowski, Kamil [1 ,2 ,3 ,4 ,5 ,6 ]
Zhang, Fan [1 ,2 ,3 ,4 ,5 ,6 ]
Wei, Kevin [2 ,3 ,4 ]
Baglaenko, Yuriy [1 ,2 ,3 ,4 ,5 ,6 ]
Brenner, Michael [2 ,3 ,4 ]
Loh, Po-ru [1 ,5 ,6 ]
Raychaudhuri, Soumya [1 ,2 ,3 ,4 ,5 ,6 ,8 ]
机构
[1] Brigham & Womens Hosp, Ctr Data Sci, 75 Francis St, Boston, MA 02115 USA
[2] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Med, Div Rheumatol, 75 Francis St, Boston, MA 02115 USA
[4] Harvard Med Sch, Boston, MA 02115 USA
[5] Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA
[6] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA
[7] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA
[8] Univ Manchester, Manchester Acad Hlth Sci Ctr, Versus Arthrit Ctr Genet & Genom, Ctr Musculoskeletal Res, Manchester, Lancs, England
基金
美国国家卫生研究院;
关键词
RNA-SEQ; GENE-EXPRESSION; IDENTITY;
D O I
10.1038/s41592-019-0619-0
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The emerging diversity of single-cell RNA-seq datasets allows for the full transcriptional characterization of cell types across a wide variety of biological and clinical conditions. However, it is challenging to analyze them together, particularly when datasets are assayed with different technologies, because biological and technical differences are interspersed. We present Harmony (https://github.com/immunogenomics/harmony), an algorithm that projects cells into a shared embedding in which cells group by cell type rather than dataset-specific conditions. Harmony simultaneously accounts for multiple experimental and biological factors. In six analyses, we demonstrate the superior performance of Harmony to previously published algorithms while requiring fewer computational resources. Harmony enables the integration of similar to 10(6) cells on a personal computer. We apply Harmony to peripheral blood mononuclear cells from datasets with large experimental differences, five studies of pancreatic islet cells, mouse embryogenesis datasets and the integration of scRNA-seq with spatial transcriptomics data.
引用
收藏
页码:1289 / +
页数:14
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