@article{9e1f35c10f83497ea870c84da0d36687,
title = "Integrated analysis of multimodal single-cell data",
abstract = "The simultaneous measurement of multiple modalities represents an exciting frontier for single-cell genomics and necessitates computational methods that can define cellular states based on multimodal data. Here, we introduce “weighted-nearest neighbor” analysis, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities. We apply our procedure to a CITE-seq dataset of 211,000 human peripheral blood mononuclear cells (PBMCs) with panels extending to 228 antibodies to construct a multimodal reference atlas of the circulating immune system. Multimodal analysis substantially improves our ability to resolve cell states, allowing us to identify and validate previously unreported lymphoid subpopulations. Moreover, we demonstrate how to leverage this reference to rapidly map new datasets and to interpret immune responses to vaccination and coronavirus disease 2019 (COVID-19). Our approach represents a broadly applicable strategy to analyze single-cell multimodal datasets and to look beyond the transcriptome toward a unified and multimodal definition of cellular identity.",
keywords = "CITE-seq, COVID-19, T cell, immune system, multimodal analysis, reference mapping, single cell genomics",
author = "Yuhan Hao and Stephanie Hao and Erica Andersen-Nissen and Mauck, {William M.} and Shiwei Zheng and Andrew Butler and Lee, {Maddie J.} and Wilk, {Aaron J.} and Charlotte Darby and Michael Zager and Paul Hoffman and Marlon Stoeckius and Efthymia Papalexi and Mimitou, {Eleni P.} and Jaison Jain and Avi Srivastava and Tim Stuart and Fleming, {Lamar M.} and Bertrand Yeung and Rogers, {Angela J.} and McElrath, {Juliana M.} and Blish, {Catherine A.} and Raphael Gottardo and Peter Smibert and Rahul Satija",
note = "Funding Information: We acknowledge Dan Littman and members of the Satija and Technology Innovation Labs for general discussion. This work was supported by the Chan Zuckerberg Initiative (EOSS-0000000082 to R.S. and HCA-A-1704-01895 to P.S. and R.S.), the NIH (RM1HG011014-01 to P.S. and R.S. 1OT2OD026673-01 to R.S. DP2HG009623-01 to R.S. R21HG009748-03 to P.S. U19AI128914 to R.G. and UM1 AI068618 to J.M.M.), the Bill and Melinda Gates Foundation (OPP1113682 to C.A.B. and A.J.R.), and the Brotman Baty Institute (to M.Z.). P.S. and R.S. conceived the study. Y.H. S.Z. A.B. C.D. M.Z. P.H. J.J. A.S. and T.S. performed computational work, supervised by R.G. and R.S. S.H. E.A.-N. W.M.M. M.J.L. A.J.W. M.S. E.P. E.P.M. L.B.F. B.Y. and A.J.R. performed experimental work, supervised by J.M.E. C.A.B. and P.S. All authors participated in interpretation and writing the manuscript. In the past three years, R.S. has worked as a consultant for Bristol-Myers Squibb, Regeneron, and Kallyope and served as an SAB member for ImmunAI, Apollo Life Sciences GmbH, Nanostring, and the NYC Pandemic Response Lab. R.G. has received consulting income from Juno Therapeutics, Takeda, Infotech Soft, Celgene, and Merck, he has received research support from Janssen Pharmaceuticals and Juno Therapeutics, and he declares ownership in CellSpace Biosciences. P.S. is a co-inventor of a patent related to this work. B.Z.Y. is an employee at BioLegend Inc. which is the exclusive licensee of the New York Genome Center patent application related to this work. Funding Information: We acknowledge Dan Littman and members of the Satija and Technology Innovation Labs for general discussion. This work was supported by the Chan Zuckerberg Initiative ( EOSS-0000000082 to R.S. and HCA-A-1704-01895 to P.S. and R.S.), the NIH ( RM1HG011014-01 to P.S. and R.S., 1OT2OD026673-01 to R.S., DP2HG009623-01 to R.S., R21HG009748-03 to P.S., U19AI128914 to R.G., and UM1 AI068618 to J.M.M.), the Bill and Melinda Gates Foundation ( OPP1113682 to C.A.B. and A.J.R.), and the Brotman Baty Institute (to M.Z.). Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = jun,
day = "24",
doi = "10.1016/j.cell.2021.04.048",
language = "English (US)",
volume = "184",
pages = "3573--3587.e29",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "13",
}