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Research Article
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Resolution of the curse of dimensionality in single-cell RNA sequencing data analysis

View ORCID ProfileYusuke Imoto, View ORCID ProfileTomonori Nakamura, Emerson G Escolar, View ORCID ProfileMichio Yoshiwaki, Yoji Kojima, Yukihiro Yabuta, Yoshitaka Katou, View ORCID ProfileTakuya Yamamoto, View ORCID ProfileYasuaki Hiraoka  Correspondence email, View ORCID ProfileMitinori Saitou  Correspondence email
Yusuke Imoto
1Institute for the Advanced Study of Human Biology, Kyoto University Institute for Advanced Study, Kyoto University, Kyoto, Japan
Roles: Conceptualization, Data curation, Software, Formal analysis, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing—original draft, review, and editing, Code implementation
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  • ORCID record for Yusuke Imoto
Tomonori Nakamura
1Institute for the Advanced Study of Human Biology, Kyoto University Institute for Advanced Study, Kyoto University, Kyoto, Japan
2Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
3The Hakubi Center for Advanced Research, Kyoto University, Kyoto, Japan
Roles: Conceptualization, Data curation, Formal analysis, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing—original draft, review, and editing
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  • ORCID record for Tomonori Nakamura
Emerson G Escolar
4Graduate School of Human Development and Environment, Kobe University, Kobe, Japan
5Center for Advanced Intelligence Project, RIKEN, Tokyo, Japan
Roles: Investigation and writing—original draft, review, and editing
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Michio Yoshiwaki
5Center for Advanced Intelligence Project, RIKEN, Tokyo, Japan
Roles: Investigation and writing—original draft, review, and editing
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  • ORCID record for Michio Yoshiwaki
Yoji Kojima
1Institute for the Advanced Study of Human Biology, Kyoto University Institute for Advanced Study, Kyoto University, Kyoto, Japan
2Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
6Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan
Roles: Data curation and investigation
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Yukihiro Yabuta
1Institute for the Advanced Study of Human Biology, Kyoto University Institute for Advanced Study, Kyoto University, Kyoto, Japan
2Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Roles: Investigation
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Yoshitaka Katou
2Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Roles: Investigation and code implementation
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Takuya Yamamoto
1Institute for the Advanced Study of Human Biology, Kyoto University Institute for Advanced Study, Kyoto University, Kyoto, Japan
5Center for Advanced Intelligence Project, RIKEN, Tokyo, Japan
6Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan
Roles: Conceptualization
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  • ORCID record for Takuya Yamamoto
Yasuaki Hiraoka
1Institute for the Advanced Study of Human Biology, Kyoto University Institute for Advanced Study, Kyoto University, Kyoto, Japan
5Center for Advanced Intelligence Project, RIKEN, Tokyo, Japan
7Center for Advanced Study, Kyoto University Institute for Advanced Study, Kyoto University, Kyoto, Japan
Roles: Conceptualization, Supervision, Funding acquisition, Investigation, Project administration, Writing—original draft, review, and editing
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  • ORCID record for Yasuaki Hiraoka
  • For correspondence: hiraoka.yasuaki.6z@kyoto-u.ac.jp saitou@anat2.med.kyoto-u.ac.jp
Mitinori Saitou
1Institute for the Advanced Study of Human Biology, Kyoto University Institute for Advanced Study, Kyoto University, Kyoto, Japan
2Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
6Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan
Roles: Conceptualization, Supervision, Funding acquisition, Project administration, Writing—original draft, review, and editing
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  • ORCID record for Mitinori Saitou
  • For correspondence: hiraoka.yasuaki.6z@kyoto-u.ac.jp saitou@anat2.med.kyoto-u.ac.jp
Published 9 August 2022. DOI: 10.26508/lsa.202201591
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Abstract

Single-cell RNA sequencing (scRNA-seq) can determine gene expression in numerous individual cells simultaneously, promoting progress in the biomedical sciences. However, scRNA-seq data are high-dimensional with substantial technical noise, including dropouts. During analysis of scRNA-seq data, such noise engenders a statistical problem known as the curse of dimensionality (COD). Based on high-dimensional statistics, we herein formulate a noise reduction method, RECODE (resolution of the curse of dimensionality), for high-dimensional data with random sampling noise. We show that RECODE consistently resolves COD in relevant scRNA-seq data with unique molecular identifiers. RECODE does not involve dimension reduction and recovers expression values for all genes, including lowly expressed genes, realizing precise delineation of cell fate transitions and identification of rare cells with all gene information. Compared with representative imputation methods, RECODE employs different principles and exhibits superior overall performance in cell-clustering, expression value recovery, and single-cell–level analysis. The RECODE algorithm is parameter-free, data-driven, deterministic, and high-speed, and its applicability can be predicted based on the variance normalization performance. We propose RECODE as a powerful strategy for preprocessing noisy high-dimensional data.

  • Received July 5, 2022.
  • Revision received July 15, 2022.
  • Accepted July 18, 2022.
  • © 2022 Imoto et al.
Creative Commons logoCreative Commons logohttps://creativecommons.org/licenses/by/4.0/

This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

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RECODE for scRNA-seq data
Yusuke Imoto, Tomonori Nakamura, Emerson G Escolar, Michio Yoshiwaki, Yoji Kojima, Yukihiro Yabuta, Yoshitaka Katou, Takuya Yamamoto, Yasuaki Hiraoka, Mitinori Saitou
Life Science Alliance Aug 2022, 5 (12) e202201591; DOI: 10.26508/lsa.202201591

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RECODE for scRNA-seq data
Yusuke Imoto, Tomonori Nakamura, Emerson G Escolar, Michio Yoshiwaki, Yoji Kojima, Yukihiro Yabuta, Yoshitaka Katou, Takuya Yamamoto, Yasuaki Hiraoka, Mitinori Saitou
Life Science Alliance Aug 2022, 5 (12) e202201591; DOI: 10.26508/lsa.202201591
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Volume 5, No. 12
December 2022
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