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The Specious Art of Single-Cell Genomics

View ORCID ProfileTara Chari, Joeyta Banerjee, 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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Joeyta Banerjee
2Department of Computing and Mathematical Sciences, 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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  • For correspondence: lpachter@caltech.edu
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Abstract

Dimensionality reduction is standard practice for filtering noise and identifying relevant dimensions in large-scale data analyses. In biology, single-cell expression studies almost always 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 analysis of cell relationships. However, there is little theoretical support for this practice. We examine the theoretical and practical implications of low-dimensional embedding of single-cell data, and find extensive distortions incurred on the global and local properties of biological patterns relative to the highdimensional, ambient space. In lieu of this, we propose semi-supervised dimensionality reduction to higher dimension, and show that such targeted reduction guided by the metadata associated with single-cell experiments provides useful latent space representations for hypothesis-driven biological discovery.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Updated analysis and explanation of two-dimensional embeddings on a greater variety of metrics. 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 September 27, 2021.
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The Specious Art of Single-Cell Genomics
Tara Chari, Joeyta Banerjee, 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, Joeyta Banerjee, Lior Pachter
bioRxiv 2021.08.25.457696; doi: https://doi.org/10.1101/2021.08.25.457696

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