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De Donno, C. ; Hediyeh-Zadeh, S. ; Moinfar, A.A. ; Wagenstetter, M. ; Zappia, L. ; Lotfollahi, M. ; Theis, F.J.

Population-level integration of single-cell datasets enables multi-scale analysis across samples.

Nat. Methods 20, 1683-1692 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
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The increasing generation of population-level single-cell atlases has the potential to link sample metadata with cellular data. Constructing such references requires integration of heterogeneous cohorts with varying metadata. Here we present single-cell population level integration (scPoli), an open-world learner that incorporates generative models to learn sample and cell representations for data integration, label transfer and reference mapping. We applied scPoli on population-level atlases of lung and peripheral blood mononuclear cells, the latter consisting of 7.8 million cells across 2,375 samples. We demonstrate that scPoli can explain sample-level biological and technical variations using sample embeddings revealing genes associated with batch effects and biological effects. scPoli is further applicable to single-cell sequencing assay for transposase-accessible chromatin and cross-species datasets, offering insights into chromatin accessibility and comparative genomics. We envision scPoli becoming an important tool for population-level single-cell data integration facilitating atlas use but also interpretation by means of multi-scale analyses.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 1548-7091
e-ISSN 1548-7105
Journal Nature Methods
Quellenangaben Volume: 20, Issue: 11, Pages: 1683-1692 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants Joachim Herz Stiftung
Helmholtz Association's Initiative and Networking Fund through Helmholtz AI
European Union (ERC)
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
Bavarian Ministry of Science and the Arts in the framework of the Bavarian Research Association 'ForInter'