Generative modeling and latent space arithmetics predict single-cell perturbation response across cell types, studies and species
Open accessAbstract
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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- 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
- green
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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