PreprintCited by 379Single-cell and spatial transcriptomicsGene expression and cancer classificationTopological and Geometric Data Analysis

The Specious Art of Single-Cell Genomics

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Chari, Tara, Pachter, Lior·2021·PLoS Computational Biology

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.

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  • Relying only on 2D embeddings can lead to misinterpretation of relationships between cells.

    “a recent study showed that relying only on 2D embeddings can lead to misinterpretation of the relationships between cells”

    From Best practices for single-cell analysis across modalities (2023) · cites this paper as [49]

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  1. [43]Badoiu M, Dhamdhere K, Gupta A, Rabinovich Y, Räcke H, Ravi R, et al. Approximation algorithms for low-distortion embeddings into low-dimensional spaces. In: SODA. vol. 5. Citeseer; 2005. p. 119– 128.
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Authors
Chari, T., & Pachter, L.
Affiliations
California Institute of Technology (US)
Corresponding author
Pachter, Lior
Venue
PLoS Computational Biology
Publisher
openRxiv
Published
2021-08-26
Volume
19
Issue
8
Pages
e1011288-e1011288
ISSN
1553-734X (ISSN-L)
OpenAlex
W4385945347
Cited by
379
References
93
Citations by year
2026: 73 · 2025: 97 · 2024: 102 · 2023: 63 · 2022: 40 · 2021: 3
FWCI
29.85
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • PLoS Computational Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by-nc)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • California Institute of Technology
  • Resnick Sustainability Institute for Science, Energy and Sustainability, California Institute of Technology
  • National Institutes of Health
  • National Institute of Mental Health (U19MH114830)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Topological and Geometric Data Analysis
Keywords
single-cell genomics, dimensionality reduction, embedding distortion, high-dimensional data, exploratory data analysis
MeSH terms
Data Analysis, Humans, Genomics

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