Gene set inference from single-cell sequencing data using a hybrid of matrix factorization and variational autoencoders

Recent advances in single-cell RNA sequencing have driven the simultaneous measurement of the expression of thousands of genes in thousands of single cells. These growing datasets allow us to model gene sets in biological networks at an unprecedented level of detail, in spite of heterogeneous cell p...

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Veröffentlicht in:	Nature machine intelligence Jg. 2; H. 12; S. 800 - 809
Hauptverfasser:	Lukassen, Soeren, Ten, Foo Wei, Adam, Lukas, Eils, Roland, Conrad, Christian
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 01.12.2020 Nature Publishing Group
Schlagworte:	631/114/1305 631/114/2114 631/114/2785 Algorithms Artificial neural networks Bias Coders Datasets Decomposition Engineering Factorization Gene expression Gene sequencing Inference Neural networks Performance evaluation Ribonucleic acid RNA
ISSN:	2522-5839
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Abstract	Recent advances in single-cell RNA sequencing have driven the simultaneous measurement of the expression of thousands of genes in thousands of single cells. These growing datasets allow us to model gene sets in biological networks at an unprecedented level of detail, in spite of heterogeneous cell populations. Here, we propose a deep neural network model that is a hybrid of matrix factorization and variational autoencoders, which we call restricted latent variational autoencoder (resVAE). The model uses weights as factorized matrices to obtain gene sets, while class-specific inputs to the latent variable space facilitate a plausible identification of cell types. This artificial neural network model seamlessly integrates functional gene set inference, experimental covariate effect isolation, and static gene identification, which we conceptually demonstrate here for four single-cell RNA sequencing datasets. The wealth of data generated by single-cell RNA sequencing can be used to identify gene sets across cells, as well as to identify specific cells. Lukassen and colleagues propose a method combining matrix factorization and variational auto encoders that can capture both cross-cell and cell-specific information.
AbstractList	Recent advances in single-cell RNA sequencing have driven the simultaneous measurement of the expression of thousands of genes in thousands of single cells. These growing datasets allow us to model gene sets in biological networks at an unprecedented level of detail, in spite of heterogeneous cell populations. Here, we propose a deep neural network model that is a hybrid of matrix factorization and variational autoencoders, which we call restricted latent variational autoencoder (resVAE). The model uses weights as factorized matrices to obtain gene sets, while class-specific inputs to the latent variable space facilitate a plausible identification of cell types. This artificial neural network model seamlessly integrates functional gene set inference, experimental covariate effect isolation, and static gene identification, which we conceptually demonstrate here for four single-cell RNA sequencing datasets.The wealth of data generated by single-cell RNA sequencing can be used to identify gene sets across cells, as well as to identify specific cells. Lukassen and colleagues propose a method combining matrix factorization and variational auto encoders that can capture both cross-cell and cell-specific information. Recent advances in single-cell RNA sequencing have driven the simultaneous measurement of the expression of thousands of genes in thousands of single cells. These growing datasets allow us to model gene sets in biological networks at an unprecedented level of detail, in spite of heterogeneous cell populations. Here, we propose a deep neural network model that is a hybrid of matrix factorization and variational autoencoders, which we call restricted latent variational autoencoder (resVAE). The model uses weights as factorized matrices to obtain gene sets, while class-specific inputs to the latent variable space facilitate a plausible identification of cell types. This artificial neural network model seamlessly integrates functional gene set inference, experimental covariate effect isolation, and static gene identification, which we conceptually demonstrate here for four single-cell RNA sequencing datasets. The wealth of data generated by single-cell RNA sequencing can be used to identify gene sets across cells, as well as to identify specific cells. Lukassen and colleagues propose a method combining matrix factorization and variational auto encoders that can capture both cross-cell and cell-specific information.
Author	Eils, Roland Conrad, Christian Adam, Lukas Lukassen, Soeren Ten, Foo Wei
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SubjectTerms	631/114/1305 631/114/2114 631/114/2785 Algorithms Artificial neural networks Bias Coders Datasets Decomposition Engineering Factorization Gene expression Gene sequencing Inference Neural networks Performance evaluation Ribonucleic acid RNA
Title	Gene set inference from single-cell sequencing data using a hybrid of matrix factorization and variational autoencoders
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