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Efficient and precise single-cell reference atlas mapping with Symphony

View ORCID ProfileJoyce B. Kang, View ORCID ProfileAparna Nathan, View ORCID ProfileFan Zhang, View ORCID ProfileNghia Millard, View ORCID ProfileLaurie Rumker, View ORCID ProfileD. Branch Moody, View ORCID ProfileIlya Korsunsky, View ORCID ProfileSoumya Raychaudhuri
doi: https://doi.org/10.1101/2020.11.18.389189
Joyce B. Kang
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
2Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
3Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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  • ORCID record for Joyce B. Kang
Aparna Nathan
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
2Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
3Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Fan Zhang
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
2Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
3Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Nghia Millard
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
2Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
3Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Laurie Rumker
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
2Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
3Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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D. Branch Moody
3Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
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Ilya Korsunsky
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
2Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
3Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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  • For correspondence: ikorsunskiy@bwh.harvard.edu soumya@broadinstitute.org
Soumya Raychaudhuri
1Center for Data Sciences, Brigham and Women’s Hospital, Boston, MA, USA
2Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
3Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
4Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
5Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
6Versus Arthritis Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
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  • For correspondence: ikorsunskiy@bwh.harvard.edu soumya@broadinstitute.org
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Abstract

Recent advances in single-cell technologies and integration algorithms make it possible to construct comprehensive reference atlases encompassing many donors, studies, disease states, and sequencing platforms. Much like mapping sequencing reads to a reference genome, it is essential to be able to map query cells onto complex, multimillion-cell reference atlases to rapidly identify relevant cell states and phenotypes. We present Symphony (https://github.com/immunogenomics/symphony), an algorithm for building integrated reference atlases of millions of cells in a convenient, portable format that enables efficient query mapping within seconds. Symphony localizes query cells within a stable low-dimensional reference embedding, facilitating reproducible downstream transfer of reference-defined annotations to the query. We demonstrate the power of Symphony by (1) mapping a multi-donor, multi-species query to predict pancreatic cell types, (2) localizing query cells along a developmental trajectory of human fetal liver hematopoiesis, and (3) inferring surface protein expression with a multimodal CITE-seq atlas of memory T cells.

Competing Interest Statement

SR receives research support from Biogen.

Footnotes

  • ↵** These authors jointly supervised this work.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 16, 2021.
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Efficient and precise single-cell reference atlas mapping with Symphony
Joyce B. Kang, Aparna Nathan, Fan Zhang, Nghia Millard, Laurie Rumker, D. Branch Moody, Ilya Korsunsky, Soumya Raychaudhuri
bioRxiv 2020.11.18.389189; doi: https://doi.org/10.1101/2020.11.18.389189
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Efficient and precise single-cell reference atlas mapping with Symphony
Joyce B. Kang, Aparna Nathan, Fan Zhang, Nghia Millard, Laurie Rumker, D. Branch Moody, Ilya Korsunsky, Soumya Raychaudhuri
bioRxiv 2020.11.18.389189; doi: https://doi.org/10.1101/2020.11.18.389189

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