Mapping single-cell data to reference atlases by transfer learning

Lotfollahi M, Naghipourfar M, Luecken MD, Khajavi M, Buettner M, Wagenstetter M, Avsec Z, Gayoso A, Yosef N, Interlandi M, Rybakov S, Misharin A, Theis FJ (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Nature Biotechnology Nature Publishing Group

Book Volume: 40

Pages Range: 121-130

Journal Issue: 1

DOI: 10.1038/s41587-021-01001-7

Abstract

Large single-cell atlases are now routinely generated to serve as references for analysis of smaller-scale studies. Yet learning from reference data is complicated by batch effects between datasets, limited availability of computational resources and sharing restrictions on raw data. Here we introduce a deep learning strategy for mapping query datasets on top of a reference called single-cell architectural surgery (scArches). scArches uses transfer learning and parameter optimization to enable efficient, decentralized, iterative reference building and contextualization of new datasets with existing references without sharing raw data. Using examples from mouse brain, pancreas, immune and whole-organism atlases, we show that scArches preserves biological state information while removing batch effects, despite using four orders of magnitude fewer parameters than de novo integration. scArches generalizes to multimodal reference mapping, allowing imputation of missing modalities. Finally, scArches retains coronavirus disease 2019 (COVID-19) disease variation when mapping to a healthy reference, enabling the discovery of disease-specific cell states. scArches will facilitate collaborative projects by enabling iterative construction, updating, sharing and efficient use of reference atlases.

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Technische Universität München (TUM) DE Germany (DE) University of California, Berkeley US United States (USA) (US) Westfälische Wilhelms-Universität (WWU) Münster DE Germany (DE) Northwestern University US United States (USA) (US)

How to cite

APA:

Lotfollahi, M., Naghipourfar, M., Luecken, M.D., Khajavi, M., Buettner, M., Wagenstetter, M.,... Theis, F.J. (2022). Mapping single-cell data to reference atlases by transfer learning. Nature Biotechnology, 40(1), 121-130. https://doi.org/10.1038/s41587-021-01001-7

MLA:

Lotfollahi, Mohammad, et al. "Mapping single-cell data to reference atlases by transfer learning." Nature Biotechnology 40.1 (2022): 121-130.

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