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

被引:3816
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
相关论文
共 48 条
  • [1] X-Box tiliding Protein 1 Is Essential for Insulin Regulation of Pancreatic α-Cell Function
    Akiyama, Masaru
    Liew, Chong Wee
    Lu, Shusheng
    Hu, Jiang
    Martinez, Rachael
    Hambro, Ben
    Kennedy, Robert T.
    Kulkarni, Rohit N.
    [J]. DIABETES, 2013, 62 (07) : 2439 - 2449
  • [2] The immune cell landscape in kidneys of patients with lupus nephritis
    Arazi, Arnon
    Rao, Deepak A.
    Berthier, Celine C.
    Davidson, Anne
    Liu, Yanyan
    Hoover, Paul J.
    Chicoine, Adam
    Eisenhaure, Thomas M.
    Jonsson, A. Helena
    Li, Shuqiang
    Lieb, David J.
    Zhang, Fan
    Slowikowski, Kamil
    Browne, Edward P.
    Noma, Akiko
    Sutherby, Danielle
    Steelman, Scott
    Smilek, Dawn E.
    Tosta, Patti
    Apruzzese, William
    Massarotti, Elena
    Dall'Era, Maria
    Park, Meyeon
    Kamen, Diane L.
    Furie, Richard A.
    Payan-Schober, Fernanda
    Pendergraft, William F., III
    McInnis, Elizabeth A.
    Buyon, Jill P.
    Petri, Michelle A.
    Putterman, Chaim
    Kalunian, Kenneth C.
    Woodle, E. Steve
    Lederer, James A.
    Hildeman, David A.
    Nusbaum, Chad
    Raychaudhuri, Soumya
    Kretzler, Matthias
    Anolik, Jennifer H.
    Brenner, Michael B.
    Wofsy, David
    Hacohen, Nir
    Diamond, Betty
    Waguespack, Dia
    Connery, Sean M.
    McMahon, Maureen A.
    McCune, William J.
    Kado, Ruba B.
    Hsu, Raymond
    Cunningham, Melissa A.
    [J]. NATURE IMMUNOLOGY, 2019, 20 (07) : 902 - +
  • [3] Gene Ontology: tool for the unification of biology
    Ashburner, M
    Ball, CA
    Blake, JA
    Botstein, D
    Butler, H
    Cherry, JM
    Davis, AP
    Dolinski, K
    Dwight, SS
    Eppig, JT
    Harris, MA
    Hill, DP
    Issel-Tarver, L
    Kasarskis, A
    Lewis, S
    Matese, JC
    Richardson, JE
    Ringwald, M
    Rubin, GM
    Sherlock, G
    [J]. NATURE GENETICS, 2000, 25 (01) : 25 - 29
  • [4] Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment
    Azizi, Elham
    Carr, Ambrose J.
    Plitas, George
    Cornish, Andrew E.
    Konopacki, Catherine
    Prabhakaran, Sandhya
    Nainys, Juozas
    Wu, Kenmin
    Kiseliovas, Vaidotas
    Setty, Manu
    Choi, Kristy
    Fromme, Rachel M.
    Phuong Dao
    McKenney, Peter T.
    Wasti, Ruby C.
    Kadaveru, Krishna
    Mazutis, Linas
    Rudensky, Alexander Y.
    Pe'er, Dana
    [J]. CELL, 2018, 174 (05) : 1293 - +
  • [5] A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure
    Baron, Maayan
    Veres, Adrian
    Wolock, Samuel L.
    Faust, Aubrey L.
    Gaujoux, Renaud
    Vetere, Amedeo
    Ryu, Jennifer Hyoje
    Wagner, Bridget K.
    Shen-Orr, Shai S.
    Klein, Allon M.
    Melton, Douglas A.
    Yanai, Itai
    [J]. CELL SYSTEMS, 2016, 3 (04) : 346 - +
  • [6] Dimensionality reduction for visualizing single-cell data using UMAP
    Becht, Etienne
    McInnes, Leland
    Healy, John
    Dutertre, Charles-Antoine
    Kwok, Immanuel W. H.
    Ng, Lai Guan
    Ginhoux, Florent
    Newell, Evan W.
    [J]. NATURE BIOTECHNOLOGY, 2019, 37 (01) : 38 - +
  • [7] Fast unfolding of communities in large networks
    Blondel, Vincent D.
    Guillaume, Jean-Loup
    Lambiotte, Renaud
    Lefebvre, Etienne
    [J]. JOURNAL OF STATISTICAL MECHANICS-THEORY AND EXPERIMENT, 2008,
  • [8] A test metric for assessing single-cell RNA-seq batch correction
    Buettner, Maren
    Miao, Zhichao
    Wolf, F. Alexander
    Teichmann, Sarah A.
    Theis, Fabian J.
    [J]. NATURE METHODS, 2019, 16 (01) : 43 - +
  • [9] Pancreatic α-cell dysfunction in diabetes
    Burcelin, R.
    Knauf, C.
    Cani, P. D.
    [J]. DIABETES & METABOLISM, 2008, 34 : S49 - S55
  • [10] Integrating single-cell transcriptomic data across different conditions, technologies, and species
    Butler, Andrew
    Hoffman, Paul
    Smibert, Peter
    Papalexi, Efthymia
    Satija, Rahul
    [J]. NATURE BIOTECHNOLOGY, 2018, 36 (05) : 411 - +