PreprintCited by 21Single-cell and spatial transcriptomicsGene Regulatory Network AnalysisGene expression and cancer classification

Generative modeling and latent space arithmetics predict single-cell perturbation response across cell types, studies and species

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Lotfollahi, M., Wolf, F. Alexander, Theis, Fabian J.·2018·bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Accurately modeling cellular response to perturbations is a central goal of computational biology. While such modeling has been proposed based on statistical, mechanistic and machine learning models in specific settings, no generalization of predictions to phenomena absent from training data (‘out-of-sample’) has yet been demonstrated. Here, we present scGen, a model combining variational autoencoders and latent space vector arithmetics for high-dimensional single-cell gene expression data. In benchmarks across a broad range of examples, we show that scGen accurately models dose and infection response of cells across cell types, studies and species. In particular, we demonstrate that scGen learns cell type and species specific response implying that it captures features that distinguish responding from non-responding genes and cells. With the upcoming availability of large-scale atlases of organs in healthy state, we envision scGen to become a tool for experimental design through in silico screening of perturbation response in the context of disease and drug treatment.

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  • First applications of deep learning to scRNA-seq are starting to emerge from dimensionality reduction to denoising.

    “First applications to scRNA‐seq are starting to emerge from dimensionality reduction to denoising (e.g. scVis: Ding et al, 2018; scGen: preprint: Lotfollahi et al, 2018; DCA: Eraslan et al, 2019).”

    From Current best practices in single-cell RNA-seq analysis: a tutorial (2019) · cites this paper as Lotfollahi et al, 2018

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Research works printed but not linked: 3

  1. Froehlich, F. et al. Efficient parameterization of large-scale mechanistic models enables drug response prediction for cancer cell lines. bioRxiv 174094 (2017).
  2. Ghahramani, A., Watt, F. M. & Luscombe, N. M. Generative adversarial networks uncover epidermal regulators and predict single cell perturbations. bioRxiv 262501 (2018).
  3. White, T. Sampling generative networks: Notes on a few effective techniques. arXiv 1609.04468 (2016). · arXiv

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Authors
Lotfollahi, M., Wolf, F. A., & Theis, F. J.
Affiliations
Helmholtz Munich (DE)
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2018-11-29
OpenAlex
W2902382430
Cited by
21
References
67
Citations by year
2023: 2 · 2021: 5 · 2020: 6 · 2019: 8
Type
posted content
Language
en
Open access
Licence
cc-by-nc-nd
Locations
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
Funders
Deutsche Forschungsgemeinschaft (Subproject A17)
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
variational autoencoder, single-cell gene expression, out-of-sample forecasting, dose-response relationship, infection response, cell type specificity, species specificity, virtual screening, experimental design

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