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A novel metric reveals previously unrecognized distortion in dimensionality reduction of scRNA-Seq data

View ORCID ProfileShamus M. Cooley, View ORCID ProfileTimothy Hamilton, View ORCID ProfileJ. Christian J. Ray, View ORCID ProfileEric J. Deeds
doi: https://doi.org/10.1101/689851
Shamus M. Cooley
1Interdepartmental Program for Bioinformatics, University of California – Los Angeles
3Institute for Quantitative and Computational Biosciences, University of California – Los Angeles
4Center for Computational Biology, University of Kansas – Lawrence
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  • ORCID record for Shamus M. Cooley
Timothy Hamilton
2Department of Integrative Biology and Physiology, University of California – Los Angeles
3Institute for Quantitative and Computational Biosciences, University of California – Los Angeles
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J. Christian J. Ray
4Center for Computational Biology, University of Kansas – Lawrence
5Department of Molecular Biosciences, University of Kansas – Lawrence
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  • For correspondence: deeds@ucla.edu jjray@ku.edu
Eric J. Deeds
2Department of Integrative Biology and Physiology, University of California – Los Angeles
3Institute for Quantitative and Computational Biosciences, University of California – Los Angeles
4Center for Computational Biology, University of Kansas – Lawrence
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  • For correspondence: deeds@ucla.edu jjray@ku.edu
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Abstract

High-dimensional data are becoming increasingly common in nearly all areas of science. Developing approaches to analyze these data and understand their meaning is a pressing issue. This is particularly true for the rapidly growing field of single-cell RNA-Seq (scRNA-Seq), a technique that simultaneously measures the expression of tens of thousands of genes in thousands to millions of single cells. The emerging consensus for analysis workflows reduces the dimensionality of the dataset before performing downstream analysis, such as assignment of cell types. One problem with this approach is that dimensionality reduction can introduce substantial distortion into the data; consider the familiar example of trying to represent the three-dimensional earth as a two-dimensional map. It is currently unclear if such distortion affects analysis of scRNA-Seq data sets. Here, we introduce a straightforward approach to quantifying this distortion by comparing the local neighborhoods of points before and after dimensionality reduction. We found that popular techniques like t-SNE and UMAP introduce substantial distortion even for relatively simple geometries such as simulated hyperspheres. For scRNA-Seq data, we found the distortion in local neighborhoods was often greater than 95% in the representations typically used for downstream analysis. This high level of distortion can readily introduce important errors into cell type identification, pseudotime ordering, and other analyses that rely on local relationships. We found that principal component analysis can generate accurate embeddings of the data, but only when using dimensionalities that are much higher than typically used in scRNA-Seq analysis. We suggest approaches to take these findings into account and call for a new generation of dimensional reduction algorithms that can accurately embed high dimensional data in its true latent dimension.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Revision addressing comments from readers.

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 September 28, 2020.
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A novel metric reveals previously unrecognized distortion in dimensionality reduction of scRNA-Seq data
Shamus M. Cooley, Timothy Hamilton, J. Christian J. Ray, Eric J. Deeds
bioRxiv 689851; doi: https://doi.org/10.1101/689851
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A novel metric reveals previously unrecognized distortion in dimensionality reduction of scRNA-Seq data
Shamus M. Cooley, Timothy Hamilton, J. Christian J. Ray, Eric J. Deeds
bioRxiv 689851; doi: https://doi.org/10.1101/689851

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