Deep learning tackles single-cell analysis-a survey of deep learning for scRNA-seq analysis.

Since its selection as the method of the year in 2013, single-cell technologies have become mature enough to provide answers to complex research questions. With the growth of single-cell profiling technologies, there has also been a significant increase in data collected from single-cell profilings, resulting in computational challenges to process these massive and complicated datasets. To address these challenges, deep learning (DL) is positioned as a competitive alternative for single-cell analyses besides the traditional machine learning approaches. Here, we survey a total of 25 DL algorithms and their applicability for a specific step in the single cell RNA-seq processing pipeline. Specifically, we establish a unified mathematical representation of variational autoencoder, autoencoder, generative adversarial network and supervised DL models, compare the training strategies and loss functions for these models, and relate the loss functions of these models to specific objectives of the data processing step. Such a presentation will allow readers to choose suitable algorithms for their particular objective at each step in the pipeline. We envision that this survey will serve as an important information portal for learning the application of DL for scRNA-seq analysis and inspire innovative uses of DL to address a broader range of new challenges in emerging multi-omics and spatial single-cell sequencing.

Characterizing Macrophages Diversity in COVID-19 Patients Using Deep Learning.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for coronavirus disease 2019 (COVID-19), has affected the lives of billions and killed millions of infected people. This virus has been demonstrated to have different outcomes among individuals, with some of them presenting a mild infection, while others present severe symptoms or even death. The identification of the molecular states related to the severity of a COVID-19 infection has become of the utmost importance to understanding the differences in critical immune response. In this study, we computationally processed a set of publicly available single-cell RNA-Seq (scRNA-Seq) data of 12 Bronchoalveolar Lavage Fluid (BALF) samples diagnosed as having a mild, severe, or no infection, and generated a high-quality dataset that consists of 63,734 cells, each with 23,916 genes. We extended the cell-type and sub-type composition identification and our analysis showed significant differences in cell-type composition in mild and severe groups compared to the normal. Importantly, inflammatory responses were dramatically elevated in the severe group, which was evidenced by the significant increase in macrophages, from 10.56% in the normal group to 20.97% in the mild group and 34.15% in the severe group. As an indicator of immune defense, populations of T cells accounted for 24.76% in the mild group and decreased to 7.35% in the severe group. To verify these findings, we developed several artificial neural networks (ANNs) and graph convolutional neural network (GCNN) models. We showed that the GCNN models reach a prediction accuracy of the infection of 91.16% using data from subtypes of macrophages. Overall, our study indicates significant differences in the gene expression profiles of inflammatory response and immune cells of severely infected patients.