Comprehensive Integration of Single-Cell Data

Tim Stuart, Andrew Butler, Paul Hoffman, Christoph Hafemeister, Efthymia Papalexi, William M. Mauck, Yuhan Hao, Marlon Stoeckius, Peter Smibert, Rahul Satija

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1888-1902.e21
JournalCell
Volume177
Issue number7
DOIs
StatePublished - Jun 13 2019

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Keywords

  • integration
  • multi-modal
  • scATAC-seq
  • scRNA-seq
  • single cell
  • single-cell ATAC sequencing
  • single-cell RNA sequencing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019). Comprehensive Integration of Single-Cell Data. Cell, 177(7), 1888-1902.e21. https://doi.org/10.1016/j.cell.2019.05.031