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Single cell RNA-seq denoising using a deep count autoencoder

By Gökcen Eraslan, Lukas M. Simon, Maria Mircea, Nikola S. Mueller, Fabian J. Theis

Posted 13 Apr 2018
bioRxiv DOI: 10.1101/300681 (published DOI: 10.1038/s41467-018-07931-2)

Single-cell RNA sequencing (scRNA-seq) has enabled researchers to study gene expression at a cellular resolution. However, noise due to amplification and dropout may obstruct analyses, so scalable denoising methods for increasingly large but sparse scRNAseq data are needed. We propose a deep count autoencoder network (DCA) to denoise scRNA-seq datasets. DCA takes the count distribution, overdispersion and sparsity of the data into account using a zero-inflated negative binomial noise model, and nonlinear gene-gene or gene-dispersion interactions are captured. Our method scales linearly with the number of cells and can therefore be applied to datasets of millions of cells. We demonstrate that DCA denoising improves a diverse set of typical scRNA-seq data analyses using simulated and real datasets. DCA outperforms existing methods for data imputation in quality and speed, enhancing biological discovery.

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