scVAE: variational auto-encoders for single-cell gene expression data

Author:

Grønbech Christopher Heje123,Vording Maximillian Fornitz3,Timshel Pascal N4,Sønderby Casper Kaae1,Pers Tune H4,Winther Ole123

Affiliation:

1. Department of Biology, Bioinformatics Centre, University of Copenhagen

2. Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, København Ø 2100, Denmark

3. Section for Cognitive Systems, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby 2800, Denmark

4. Faculty of Health and Medical Sciences, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, København N 2200, Denmark

Abstract

Abstract Motivation Models for analysing and making relevant biological inferences from massive amounts of complex single-cell transcriptomic data typically require several individual data-processing steps, each with their own set of hyperparameter choices. With deep generative models one can work directly with count data, make likelihood-based model comparison, learn a latent representation of the cells and capture more of the variability in different cell populations. Results We propose a novel method based on variational auto-encoders (VAEs) for analysis of single-cell RNA sequencing (scRNA-seq) data. It avoids data preprocessing by using raw count data as input and can robustly estimate the expected gene expression levels and a latent representation for each cell. We tested several count likelihood functions and a variant of the VAE that has a priori clustering in the latent space. We show for several scRNA-seq datasets that our method outperforms recently proposed scRNA-seq methods in clustering cells and that the resulting clusters reflect cell types. Availability and implementation Our method, called scVAE, is implemented in Python using the TensorFlow machine-learning library, and it is freely available at https://github.com/scvae/scvae. Supplementary information Supplementary data are available at Bioinformatics online.

Funder

Lundbeck Foundation

Novo Nordisk Foundation

Novo Nordisk Foundation Center for Basic Metabolic Research

Danish Ministry of Higher Education and Science [Elite Research Travel Grant 2018]

Publisher

Oxford University Press (OUP)

Subject

Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability

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