A deep neural network to de-noise single-cell RNA sequencing data

Single-cell RNA sequencing (scRNA-seq), a powerful technique for investigating the transcriptome of individual cells, enables the discovery of heterogeneous cell populations, rare cell types, and transcriptional dynamics in separate cells. Yet, scRNA-seq data analysis is limited by the problem of measurement dropouts, i.e., genes displaying zero expression levels. We introduce ZiPo, a deep artificial neural network for rate estimation and library size prediction in scRNA-seq data which incorporates adjustable zero inflation in the distribution to capture the dropouts. ZiPo builds upon established concepts, including using deep autoencoders and adopting the Poisson and negative binomial distributions, by taking advantage of novel strategies, including library size prediction and residual connections, to improve the overall performance. A significant innovation of ZiPo is the introduction of a scale-invariant loss term, making the weights sparse and, hence, the model biologically more interpretable. ZiPo quickly handles vast singular and mixed datasets, with the processing time directly proportional to the number of cells. In this paper, we demonstrate the power of ZiPo on three datasets and show its advantages over other current techniques. The code used to produce the results in this manuscript is available at https://bitbucket.org/habilzare/alzheimer/src/master/code/deep/ZiPo/.