Cited by 472Single-cell and spatial transcriptomicsBioinformatics and Genomic NetworksGene Regulatory Network Analysis

Computational principles and challenges in single-cell data integration

Argelaguet, Ricard, Cuomo, Anna S. E., Stegle, Oliver, Marioni, John C.·2021·Nature Biotechnology

Abstract

The development of single-cell multimodal assays provides a powerful tool for investigating multiple dimensions of cellular heterogeneity, enabling new insights into development, tissue homeostasis and disease. A key challenge in the analysis of single-cell multimodal data is to devise appropriate strategies for tying together data across different modalities. The term 'data integration' has been used to describe this task, encompassing a broad collection of approaches ranging from batch correction of individual omics datasets to association of chromatin accessibility and genetic variation with transcription. Although existing integration strategies exploit similar mathematical ideas, they typically have distinct goals and rely on different principles and assumptions. Consequently, new definitions and concepts are needed to contextualize existing methods and to enable development of new methods.

Integrity signals

Registry

Crossref · 10.1038/s41587-021-00895-7

Cites

156 of 156 references verified0 citation errors · 0 not checkable

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Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Holistic representations of cells can be obtained only with analyses across modalities, in which several modalities of the same cells are jointly examined.

    “Holistic representations of cells can be obtained only with analyses across modalities245, whereby several modalities of the same cells are jointly examined.”

    From Best practices for single-cell analysis across modalities (2023) · cites this paper as [245]

  • A common task in single-cell analysis is to eliminate batch effects without removing meaningful biological differences, allowing for data integration.

    “Hence, a common task in single-cell analysis is to eliminate batch effects without removing meaningful biological differences, allowing for data integration [13, 14, 15].”
  • Much of the work in single-cell biology is inherently exploratory, where labels may not be available a priori.

    “However, much of the work in single-cell biology is inherently exploratory, where labels may not be available a priori .”

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Authors
Argelaguet, R., Cuomo, A. S. E., Stegle, O., & Marioni, J. C.
Affiliations
  • Babraham Institute (GB)
  • European Bioinformatics Institute (GB)
  • German Cancer Research Center (DE)
Corresponding author
  • Argelaguet, Ricard
  • Cuomo, Anna S. E.
  • Stegle, Oliver
  • Marioni, John C.
Venue
Nature Biotechnology
Published
2021-05-03
Volume
39
Issue
10
Pages
1202-1215
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W3159800610
Cited by
472
References
156
Citations by year
2026: 103 · 2025: 89 · 2024: 94 · 2023: 94 · 2022: 71 · 2021: 21
FWCI
7.35
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • EMBL International PhD Programme
  • European Commission (810296)
  • Core funding from EMBL and DKFZ
  • Cancer Research UK (C9545/A29580)
  • Core funding from CRUK (grant number listed above) and EMBL
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords
single-cell data integration, batch effect correction, chromatin accessibility, transcription, cellular heterogeneity, integration strategies
MeSH terms
Animals, Chromatin, Data Interpretation, Statistical, Humans, Genetic Variation, Computational Biology, Genomics, Precision Medicine, Single-Cell Analysis

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