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Learning interpretable latent autoencoder representations with annotations of feature sets

Sergei Rybakov, View ORCID ProfileMohammad Lotfollahi, View ORCID ProfileFabian J. Theis, View ORCID ProfileF. Alexander Wolf
doi: https://doi.org/10.1101/2020.12.02.401182
Sergei Rybakov
1Institute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany
2Department of Mathematics, Technical University of Munich, Munich, Germany
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  • For correspondence: sergei.rybakov@helmholtz-muenchen.de fabian.theis@helmholtz-muenchen.de alex.wolf@helmholtz-muenchen.de
Mohammad Lotfollahi
1Institute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany
3School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany
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Fabian J. Theis
1Institute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany
2Department of Mathematics, Technical University of Munich, Munich, Germany
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  • For correspondence: sergei.rybakov@helmholtz-muenchen.de fabian.theis@helmholtz-muenchen.de alex.wolf@helmholtz-muenchen.de
F. Alexander Wolf
1Institute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany
4Cellarity Inc., Cambridge, MA, USA
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  • For correspondence: sergei.rybakov@helmholtz-muenchen.de fabian.theis@helmholtz-muenchen.de alex.wolf@helmholtz-muenchen.de
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Abstract

Existing methods for learning latent representations for single-cell RNA-seq data are based on autoencoders and factor models. However, representations learned by autoencoders are hard to interpret and representations learned by factor models have limited flexibility. Here, we introduce a framework for learning interpretable autoencoders based on regularized linear decoders. It decomposes variation into interpretable components using prior knowledge in the form of annotated feature sets obtained from public databases. Through this, it provides an alternative to enrichment techniques and factor models for the task of explaining observed variation with biological knowledge. Benchmarking our model on two single-cell RNA-seq datasets, we demonstrate how our model outperforms an existing factor model regarding scalability while maintaining interpretability.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Presented at the 15th Machine Learning in Computational Biology (MLCB) meeting. Copyright 2020 by the author(s).

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 03, 2020.
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Learning interpretable latent autoencoder representations with annotations of feature sets
Sergei Rybakov, Mohammad Lotfollahi, Fabian J. Theis, F. Alexander Wolf
bioRxiv 2020.12.02.401182; doi: https://doi.org/10.1101/2020.12.02.401182
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Learning interpretable latent autoencoder representations with annotations of feature sets
Sergei Rybakov, Mohammad Lotfollahi, Fabian J. Theis, F. Alexander Wolf
bioRxiv 2020.12.02.401182; doi: https://doi.org/10.1101/2020.12.02.401182

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