Cited by 280Single-cell and spatial transcriptomicsGene expression and cancer classificationGene Regulatory Network Analysis

DestVI identifies continuums of cell types in spatial transcriptomics data

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Lopez, Romain, Li, Baoguo, Keren-Shaul, Hadas, Boyeau, Pierre, Kedmi, Merav, Pilzer, David, Jelinski, Adam, Yofe, Ido +9 more·2022·Nature Biotechnology

Published version of a preprint

Abstract

Most spatial transcriptomics technologies are limited by their resolution, with spot sizes larger than that of a single cell. Although joint analysis with single-cell RNA sequencing can alleviate this problem, current methods are limited to assessing discrete cell types, revealing the proportion of cell types inside each spot. To identify continuous variation of the transcriptome within cells of the same type, we developed Deconvolution of Spatial Transcriptomics profiles using Variational Inference (DestVI). Using simulations, we demonstrate that DestVI outperforms existing methods for estimating gene expression for every cell type inside every spot. Applied to a study of infected lymph nodes and of a mouse tumor model, DestVI provides high-resolution, accurate spatial characterization of the cellular organization of these tissues and identifies cell-type-specific changes in gene expression between different tissue regions or between conditions. DestVI is available as part of the open-source software package scvi-tools (https://scvi-tools.org). DestVI models continuous cell states in spatial transcriptomics data.

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  • DestVI proposed a framework that jointly learned latent representations of scRNA-seq datasets and spatial spot expression datasets to deconvolute cell-type proportions and related transcriptional states in single spots.

    “DestVI proposed a framework that jointly learned the latent representations of scRNA-seq datasets and spatial spot expression datasets to deconvolute cell-type proportions and related transcriptional states in single spots [126].”

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Research works printed but not linked: 5

  1. Kingma, D. P. & Welling, M. Auto-encoding variational Bayes. Int. Conf. Learning Representations (2014).
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  5. Ba, J. L., Kiros, J. R. & Hinton, G. E. Layer normalization. Preprint at https://arxiv.org/abs/1607.06450 (2016). · arXiv

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Authors
Lopez, R., Li, B., Keren-Shaul, H., Boyeau, P., Kedmi, M., Pilzer, D., Jelinski, A., Yofe, I., David, E., Wagner, A., Ergen, C., Addadi, Y., Golani, O., Ronchese, F., Jordan, M. I., Amit, I., & Yosef, N.
Affiliations
  • University of California, Berkeley (US)
  • Weizmann Institute of Science (IL)
  • Malaghan Institute of Medical Research (NZ)
  • Ragon Institute of MGH, MIT and Harvard (US)
Corresponding author
  • Amit, Ido
  • Yosef, Nir
Venue
Nature Biotechnology
Published
2022-04-21
Volume
40
Issue
9
Pages
1360-1369
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W4224218779
Cited by
276
References
98
Citations by year
2026: 63 · 2025: 67 · 2024: 71 · 2023: 40 · 2022: 25 · 2021: 9
FWCI
17.06
Type
journal article
Language
en
Open access
Locations
  • Nature Biotechnology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (U19 AI090023)
  • Chan-Zuckerberg BioHub
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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords
spatial transcriptomics, cell type deconvolution, variational inference, single-cell RNA sequencing, gene expression estimation, lymph node infection, mouse tumor model, cell organization
MeSH terms
Exome Sequencing, Animals, Neoplasms, Software, Gene Expression Profiling, Mice, Single-Cell Analysis, Transcriptome

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