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Identifying cellular-to-phenotype associations by elucidating hierarchical relationships in high-dimensional cytometry data

View ORCID ProfileAdam Chan, Wei Jiang, Emily Blyth, View ORCID ProfileJean Yang, View ORCID ProfileEllis Patrick
doi: https://doi.org/10.1101/2021.07.08.451609
Adam Chan
1School of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, Australia
2Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
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Wei Jiang
3Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
4Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
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Emily Blyth
3Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
4Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia
5Blood Transplant and Cell Therapies Program, Department of Haematology, Westmead Hospital, NSW Australia
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Jean Yang
1School of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, Australia
2Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia
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Ellis Patrick
1School of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales, Australia
3Centre for Cancer Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
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  • For correspondence: ellis.patrick@sydney.edu.au
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Abstract

High-throughput single cell technologies hold the promise of discovering novel cellular relationships with disease. However, analytical workflows constructed for these technologies to associate cell proportions with disease often employ unsupervised clustering techniques that overlook the valuable hierarchical structures that have been used to define cell types. We present treekoR, a framework that empirically recapitulates these structures, facilitating multiple quantifications and comparisons of cell type proportions. Our results from twelve case studies reinforce the importance of quantifying proportions relative to parent populations in the analyses of cytometry data — as failing to do so can lead to missing important biological insights.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Figure resolution updated; declarations updated; some grammatical nuances updated

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 16, 2021.
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Identifying cellular-to-phenotype associations by elucidating hierarchical relationships in high-dimensional cytometry data
Adam Chan, Wei Jiang, Emily Blyth, Jean Yang, Ellis Patrick
bioRxiv 2021.07.08.451609; doi: https://doi.org/10.1101/2021.07.08.451609
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Identifying cellular-to-phenotype associations by elucidating hierarchical relationships in high-dimensional cytometry data
Adam Chan, Wei Jiang, Emily Blyth, Jean Yang, Ellis Patrick
bioRxiv 2021.07.08.451609; doi: https://doi.org/10.1101/2021.07.08.451609

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