PreprintCited by 13,200Single-cell and spatial transcriptomicsGene expression and cancer classificationGenomics and Phylogenetic Studies

Integrated analysis of single cell transcriptomic data across conditions, technologies, and species

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Butler, Andrew, Satija, Rahul·2017·Nature Biotechnology

Preprint — published as 10.1038/nbt.4096 · Paper page

Abstract

Single cell RNA-seq (scRNA-seq) has emerged as a transformative tool to discover and define cellular phenotypes. While computational scRNA-seq methods are currently well suited for experiments representing a single condition, technology, or species, analyzing multiple datasets simultaneously raises new challenges. In particular, traditional analytical workflows struggle to align subpopulations that are present across datasets, limiting the possibility for integrated or comparative analysis. Here, we introduce a new computational strategy for scRNA-seq alignment, utilizing common sources of variation to identify shared subpopulations between datasets as part of our R toolkit Seurat. We demonstrate our approach by aligning scRNA-seq datasets of PBMCs under resting and stimulated conditions, hematopoietic progenitors sequenced across two profiling technologies, and pancreatic cell ‘atlases’ generated from human and mouse islets. In each case, we learn distinct or transitional cell states jointly across datasets, and can identify subpopulations that could not be detected by analyzing datasets independently. We anticipate that these methods will serve not only to correct for batch or technology-dependent effects, but also to facilitate general comparisons of scRNA-seq datasets, potentially deepening our understanding of how distinct cell states respond to perturbation, disease, and evolution. Availability: Installation instructions, documentation, and tutorials are available at http://www.satijalab.org/seurat

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  • Using a publicly available adult dataset, the study identified 14 inhibitory interneuron subpopulations that encompass known anatomically and physiologically defined subtypes.

    “utilizing a publicly available dataset22,23, we identified 14 inhibitory interneuron subpopulations that encompass known anatomically and physiologically defined subtypes24,25”

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Authors
Butler, A., & Satija, R.
Affiliations
New York Genome Center (US)
Corresponding author
Satija, Rahul
Venue
Nature Biotechnology
Publisher
openRxiv
Published
2017-07-18
Volume
36
Issue
5
Pages
411-420
ISSN
0733-222X (ISSN-L)
OpenAlex
W2794480084
Cited by
13,200
References
53
Citations by year
2026: 1305 · 2025: 1837 · 2024: 2122 · 2023: 1921 · 2022: 1786 · 2021: 1832 · 2020: 1417 · 2019: 760 · 2018: 205 · 2017: 5 · 2015: 1 · 2014: 1 · 2013: 1
FWCI
380.84
Type
journal article
Language
en
Open access
Locations
  • Nature Biotechnology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Science Foundation (1342536)
  • National Institutes of Health (1dp2hg009623-01)
  • National Human Genome Research Institute (DP2-HG-009623)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
Keywords
Seurat, peripheral blood mononuclear cells, hematopoietic progenitor cells, pancreatic islets, cell state transitions, statistical power
MeSH terms
Data Analysis, Animals, Humans, Leukocytes, Mononuclear, Software, Sequence Analysis, RNA, Gene Expression Profiling, Computers, Molecular, Mice, Single-Cell Analysis, High-Throughput Nucleotide Sequencing, Transcriptome

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