Cited by 703Single-cell and spatial transcriptomicsGene Regulatory Network AnalysisGene expression and cancer classification

Probabilistic harmonization and annotation of single‐cell transcriptomics data with deep generative models

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Xu, Chenling, Lopez, Romain, Mehlman, Edouard, Regier, Jeffrey, Jordan, Michael I, Yosef, Nir·2021·Molecular Systems Biology

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Abstract

As the number of single‐cell transcriptomics datasets grows, the natural next step is to integrate the accumulating data to achieve a common ontology of cell types and states. However, it is not straightforward to compare gene expression levels across datasets and to automatically assign cell type labels in a new dataset based on existing annotations. In this manuscript, we demonstrate that our previously developed method, scVI, provides an effective and fully probabilistic approach for joint representation and analysis of scRNA‐seq data, while accounting for uncertainty caused by biological and measurement noise. We also introduce single‐cell ANnotation using Variational Inference (scANVI), a semi‐supervised variant of scVI designed to leverage existing cell state annotations. We demonstrate that scVI and scANVI compare favorably to state‐of‐the‐art methods for data integration and cell state annotation in terms of accuracy, scalability, and adaptability to challenging settings. In contrast to existing methods, scVI and scANVI integrate multiple datasets with a single generative model that can be directly used for downstream tasks, such as differential expression. Both methods are easily accessible through scvi‐tools.

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  • 125 supertypes represented cell types that could be reliably reidentified in reference datasets (mean F1 score = 0.91) using hierarchical probabilistic Bayesian mapping.

    “To map SEA-AD data to cell types consistently across all 84 donors, we first defined robust transcriptional types, named supertypes, in the BICCN reference; 125 supertypes represented cell types that could be reliably reidentified in reference datasets (mean F1 score = 0.91) using hierarchical probabilistic Bayesian mapping47,48(Extended Data Fig. 5a,b).”

    From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [48]

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Research works printed but not linked: 4

  1. Goldberger J, Ben‐Reuven E (2017) Training deep neural‐networks using a noise adaptation layer. In Proceedings of the International Conference on Learning Representations, Toulon, France
  2. Kingma DP, Mohamed S, Jimenez Rezende D, Welling M (2014) Semisupervised learning with deep generative models. Adv Neural Inf Process Syst 27: 3581–3589
  3. Kingma DP, Welling M (2014) Auto‐encoding variational Bayes. In Proceedings of the International Conference on Learning Representations, Banff, Canada
  4. Louizos C, Swersky K, Li Y, Welling M, Zemel R (2016) The variational fair autoencoder. In Proceedings of the International Conference on Learning Representations, San Juan, Puerto Rico

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Authors
Xu, C., Lopez, R., Mehlman, E., Regier, J., Jordan, M. I., & Yosef, N.
Affiliations
  • University of California, Berkeley (US)
  • École Polytechnique (FR)
  • University of Michigan (US)
  • Harvard University (US)
Corresponding author
Yosef, Nir
Venue
Molecular Systems Biology
Published
2021-01-01
Volume
17
Issue
1
Pages
e9620-e9620
ISSN
1744-4292 (ISSN-L)
OpenAlex
W3121168830
Cited by
691
References
83
Citations by year
2026: 206 · 2025: 188 · 2024: 126 · 2023: 91 · 2022: 44 · 2021: 29 · 2020: 6 · 2019: 1
FWCI
23.55
Type
journal article
Language
en
Open access
Locations
  • Molecular Systems Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (U19 AI090023)
  • NIH | National Institute of Mental Health (U19 MH114821)
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 Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
Keywords
single-cell transcriptomics, data integration, cell type annotation, scVI, scANVI, variational inference, deep generative models, stochastic modeling, uncertainty quantification, semi-supervised learning, differential gene expression
MeSH terms
Supervised Machine Learning, Humans, Sequence Analysis, RNA, Computational Biology, Gene Expression Profiling, Databases, Genetic, Molecular Sequence Annotation, Single-Cell Analysis

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