@article{c36a666216d1475fbcb6c35903e31570,
title = "Comprehensive Integration of Single-Cell Data",
abstract = "Single-cell transcriptomics has transformed our ability to characterize cell states, but deep biological understanding requires more than a taxonomic listing of clusters. As new methods arise to measure distinct cellular modalities, a key analytical challenge is to integrate these datasets to better understand cellular identity and function. Here, we develop a strategy to “anchor” diverse datasets together, enabling us to integrate single-cell measurements not only across scRNA-seq technologies, but also across different modalities. After demonstrating improvement over existing methods for integrating scRNA-seq data, we anchor scRNA-seq experiments with scATAC-seq to explore chromatin differences in closely related interneuron subsets and project protein expression measurements onto a bone marrow atlas to characterize lymphocyte populations. Lastly, we harmonize in situ gene expression and scRNA-seq datasets, allowing transcriptome-wide imputation of spatial gene expression patterns. Our work presents a strategy for the assembly of harmonized references and transfer of information across datasets.",
keywords = "integration, multi-modal, scATAC-seq, scRNA-seq, single cell, single-cell ATAC sequencing, single-cell RNA sequencing",
author = "Tim Stuart and Andrew Butler and Paul Hoffman and Christoph Hafemeister and Efthymia Papalexi and Mauck, {William M.} and Yuhan Hao and Marlon Stoeckius and Peter Smibert and Rahul Satija",
note = "Funding Information: This work was supported by an NIH New Innovator Award ( 1DP2HG009623- 01 ; R.S.) NIH Human Biomolecular Atlas Program Award ( 1OT2OD026673-01 ) and R01 ( 5R01MH071679-12 ; R.S.), Chan Zuckerberg Awards HCA-A-1704-01895 (R.S. and P.S.) and HCA2-A-1708-02755 (R.S), and an NSF Graduate Fellowship ( DGE1342536 ; A.B.). We acknowledge members of the Satija Lab, NYGC Technology Innovation lab, Claude Desplan, Dan Littman, and Gord Fishell for helpful comments and discussion and Josh Batson and Will Allen for sharing data and metadata. Funding Information: This work was supported by an NIH New Innovator Award (1DP2HG009623- 01; R.S.) NIH Human Biomolecular Atlas Program Award (1OT2OD026673-01) and R01 (5R01MH071679-12; R.S.), Chan Zuckerberg Awards HCA-A-1704-01895 (R.S. and P.S.) and HCA2-A-1708-02755 (R.S), and an NSF Graduate Fellowship (DGE1342536; A.B.). We acknowledge members of the Satija Lab, NYGC Technology Innovation lab, Claude Desplan, Dan Littman, and Gord Fishell for helpful comments and discussion and Josh Batson and Will Allen for sharing data and metadata. T.S. A.B. and R.S. conceived the research. T.S. and A.B. led computational work assisted by P.H. C.H. and Y.H. and supervised by R.S. E.P. and M.S. led experimental work with assistance from W.M.M. and supervised by P.S. All authors participated in interpretation and writing the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = jun,
day = "13",
doi = "10.1016/j.cell.2019.05.031",
language = "English (US)",
volume = "177",
pages = "1888--1902.e21",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",
}