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The Specious Art of Single-Cell Genomics

View ORCID ProfileTara Chari, View ORCID ProfileLior Pachter
doi: https://doi.org/10.1101/2021.08.25.457696
Tara Chari
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California
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Lior Pachter
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California
2Department of Computing and Mathematical Sciences, California Institute of Technology, Pasadena, California
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Abstract

Dimensionality reduction is standard practice for filtering noise and identifying relevant features in large-scale data analyses. In biology, single-cell genomics studies typically begin with reduction to two or three dimensions to produce ‘all-in-one’ visuals of the data that are amenable to the human eye, and these are subsequently used for qualitative and quantitative exploratory analysis. However, there is little theoretical support for this practice, and we show that extreme dimension reduction, from hundreds or thousands of dimensions to two, inevitably induces significant distortion of high-dimensional datasets. We therefore examine the practical implications of low-dimensional embedding of single-cell data, and find that extensive distortions and inconsistent practices make such embeddings counter-productive for exploratory, biological analyses. In lieu of this, we discuss alternative approaches for conducting targeted embedding and feature exploration, to enable hypothesis-driven biological discovery.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Manuscript updated to include broader discussion of uses and practices for 2D embedding in single-cell genomics, covering more relevant applications in results, and alternative strategies in the discussion. Supplemental files updated accordingly.

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 4.0 International license.
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Posted December 22, 2022.
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The Specious Art of Single-Cell Genomics
Tara Chari, Lior Pachter
bioRxiv 2021.08.25.457696; doi: https://doi.org/10.1101/2021.08.25.457696
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The Specious Art of Single-Cell Genomics
Tara Chari, Lior Pachter
bioRxiv 2021.08.25.457696; doi: https://doi.org/10.1101/2021.08.25.457696

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