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DestVI identifies continuums of cell types in spatial transcriptomics data
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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 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].”
From Challenges in AI-driven Biomedical Multimodal Data Fusion and Analysis (2025) · cites this paper as [126]
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“Despite the many 107 deconvolution methods(26-31) developed for spatial transcriptomics (ST) data, few recognize 108 spatial dependency explicitly.”
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“Each spot is independently assigned with the number of cells (5-15) and the number of cell types (1-5) uniformly, and the final cell-type assignment is determined by a uniform Dirichlet distribution.”
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“…(for 10x Visium and Slide-seq) (Andersson et al. 2020, Elosua-Bayes et al. 2021, Song and Su 2021, Cable et al. 2022, Kleshchevnikov et al. 2022, Lopez et al. 2022, Miller et al. 2022, Sun et al. 2022, Hao et al. 2024), predicting the spatial distribution of RNA transcripts (Lopez et al. 2019,…”
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“In this work, we benchmark five well-performing spatial transcriptomics deconvolution methods (Cell2location (Kleshchevnikov et al. 2022), RCTD (Cable et al. 2022), Tangram (Biancalani et al. 2021), SpatialDWLS (Dong and Yuan 2021), and DestVI (Lopez et al. 2022)) and assess whether they can be readily applied to emer…”
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“…2021), using seeded non-negative matrix factorization, and Deconvolution of Spatial Tran-scriptomics pro fi les using Variational Inference (DestVI) (Lopez et al, 2022), applying variational inference with autoencoder architectures, may help mitigate contamination and provide cleaner estimates of…”
Zhang, Y., Ming, W., Yu, B., Wang, L., Lu, K., Xu, L., Ni, Y., Deng, R., & Chen, D. (2025) · Cell Genomics · doi:10.1016/j.xgen.2025.101105 · Cited by 6
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“DestVI (Lopez et al. 2022) utilizes the continuous variation of transcriptome within cells of the same type, which facilitates optimization of mixture of cell types.”
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“…as a proxy for TF activity, STAN estimates spatially informed TF activity, which is further refined by incorporating cell-type deconvolution approaches (e.g. Cell2location [ 16 ], DestVI [ 17 ], Tangram [ 18 ], Stereoscope [ 19 ], RCTD [ 20 ], and others) to identify cell-type-specific TFs.”
Sang-aram, C., Browaeys, R., Seurinck, R., & Saeys, Y. (2023) · eLife · doi:10.7554/elife.88431.1 · Cited by 4
SIMVI reveals intrinsic and spatial-induced states in spatial omics dataPreprint
Dong, M., Su, D. G., Kluger, H. M., Fan, R., & Kluger, Y. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.08.28.554970 · Cited by 4
“To address these limitations, advanced deconvolution methods such as Tangram [51], CARD [52], and DestVI [53] could help reveal the single-cell profile within each pixel by using scRNA-seq references.”
Zhang, D., Yu, N., Li, W., Sun, X. G., Zou, Q., Li, X., Liu, Z., Yuan, Z., Zhang, W., & Gao, R. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.22.581503 · Cited by 4
Generative modeling of spatially resolved perturbation responses with CONCERTPreprint
Lin, X., Kong, Z., Fu, B., Ghosh, S., Kellis, M., & Žitnik, M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.08.686890 · Cited by 6
“In parallel, spatial transcriptomics methods address deconvolution and spatial patterning [25–33] yet do not analyze responses to perturbations.”
Robust Spatial Cell‐Type Deconvolution with Qualitative Reference for Spatial Transcriptomics
Dong, Q., Yang, Y., Luo, Z., Shen, H., Shi, X., & Liu, J. (2025) · Small Methods · doi:10.1002/smtd.202401145 · Cited by 4
Mouse-Specific Single cell cytokine activity prediction and Estimation (MouSSE)
Javaid, A., & Frost, H. R. (2025) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1013475 · Cited by 3
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Doan, L. M. T., Verma, S., Eftekhari, N., Angione, C., & Occhipinti, A. (2025) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2025.111195 · Cited by 4
Reconstructing single-cell resolution from spatial transcriptomics with CellRefiner
Bourgain-Chang, E., Kuang, X., Cang, Z., & Nie, Q. H. (2026) · Nature Communications · doi:10.1038/s41467-026-70090-2 · Cited by 3
Multimodal spatial omics: From data acquisition to computational integration
Işık, E. B., Usta, Y. H., Riazi, M., Liu, H., Roach, W., Zhou, H., Nicolaou, A., Rattray, M., & Georgaka, S. (2026) · Patterns · doi:10.1016/j.patter.2026.101592 · Cited by 5
“98 Hybrid approaches combine probabilistic inference with deep learning for spatial prediction tasks.”
Interpretable spatial multi-omics data integration and dimensionality reduction with SpaMV
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Masked adversarial neural network for cell type deconvolution in spatial transcriptomics
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Xu, Y., Yu, B., Chen, X., Peng, A., Tao, Q., He, Y., Wang, Y., & Li, X. (2025) · National Science Review · doi:10.1093/nsr/nwaf030 · Cited by 3
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Decoding spatial transcriptomics: Current trends and future prospects in data analysis methodologies
Li, R., Chen, X., & Yang, X. (2024) · Chinese Science Bulletin (Chinese Version) · doi:10.1360/tb-2024-0332 · Cited by 3
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Metadata
- 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
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2022-04-21
- Volume
- 40
- Issue
- 9
- Pages
- 1360-1369
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC9756396
- OpenAlex
- W4224218779
- Semantic Scholar
- d88d598ef4cdd976986d65e6f9849e5b7b223ecb
- Cited by
- 276
- References
- 98
- Citations by year
- 2026: 63 · 2025: 67 · 2024: 71 · 2023: 40 · 2022: 25
- FWCI
- 17.06
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- 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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