Computational principles and challenges in single-cell data integration
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.
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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].”
From Assessing the limits of zero-shot foundation models in single-cell biology (2023) · cites this paper as [14]
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 .”
From Assessing the limits of zero-shot foundation models in single-cell biology (2023) · cites this paper as [14]
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Methods and applications for single-cell and spatial multi-omics
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Self-citation
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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