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      Adversarial dense graph convolutional networks for single-cell classification

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      , , , ,
      Bioinformatics
      Oxford University Press

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          Abstract

          Motivation

          In single-cell transcriptomics applications, effective identification of cell types in multicellular organisms and in-depth study of the relationships between genes has become one of the main goals of bioinformatics research. However, data heterogeneity and random noise pose significant difficulties for scRNA-seq data analysis.

          Results

          We have proposed an adversarial dense graph convolutional network architecture for single-cell classification. Specifically, to enhance the representation of higher-order features and the organic combination between features, dense connectivity mechanism and attention-based feature aggregation are introduced for feature learning in convolutional neural networks. To preserve the features of the original data, we use a feature reconstruction module to assist the goal of single-cell classification. In addition, HNNVAT uses virtual adversarial training to improve the generalization and robustness. Experimental results show that our model outperforms the existing classical methods in terms of classification accuracy on benchmark datasets.

          Availability and implementation

          The source code of HNNVAT is available at https://github.com/DisscLab/HNNVAT.

          Supplementary information

          Supplementary data are available at Bioinformatics online.

          Graphical Abstract

          Graphical Abstract

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          Most cited references22

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          Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage

          Tissue fibrosis is a major cause of mortality that results from the deposition of matrix proteins by an activated mesenchyme. Macrophages accumulate in fibrosis, but the role of specific subgroups in supporting fibrogenesis has not been investigated in vivo. Here we used single-cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of macrophages in bleomycin-induced lung fibrosis in mice. A novel computational framework for the annotation of scRNA-seq by reference to bulk transcriptomes (SingleR) enabled the subclustering of macrophages and revealed a disease-associated subgroup with a transitional gene expression profile intermediate between monocyte-derived and alveolar macrophages. These CX3CR1+SiglecF+ transitional macrophages localized to the fibrotic niche and had a profibrotic effect in vivo. Human orthologues of genes expressed by the transitional macrophages were upregulated in samples from patients with idiopathic pulmonary fibrosis. Thus, we have identified a pathological subgroup of transitional macrophages that are required for the fibrotic response to injury.
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            A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure.

            Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells. We detected subpopulations of ductal cells with distinct expression profiles and validated their existence with immuno-histochemistry stains. Moreover, among human beta- cells, we detected heterogeneity in the regulation of genes relating to functional maturation and levels of ER stress. Finally, we deconvolved bulk gene expression samples using the single-cell data to detect disease-associated differential expression. Our dataset provides a resource for the discovery of novel cell type-specific transcription factors, signaling receptors, and medically relevant genes.
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              A Comprehensive Survey on Graph Neural Networks

              Deep learning has revolutionized many machine learning tasks in recent years, ranging from image classification and video processing to speech recognition and natural language understanding. The data in these tasks are typically represented in the Euclidean space. However, there is an increasing number of applications, where data are generated from non-Euclidean domains and are represented as graphs with complex relationships and interdependency between objects. The complexity of graph data has imposed significant challenges on the existing machine learning algorithms. Recently, many studies on extending deep learning approaches for graph data have emerged. In this article, we provide a comprehensive overview of graph neural networks (GNNs) in data mining and machine learning fields. We propose a new taxonomy to divide the state-of-the-art GNNs into four categories, namely, recurrent GNNs, convolutional GNNs, graph autoencoders, and spatial-temporal GNNs. We further discuss the applications of GNNs across various domains and summarize the open-source codes, benchmark data sets, and model evaluation of GNNs. Finally, we propose potential research directions in this rapidly growing field.
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                Author and article information

                Contributors
                Role: Associate Editor
                Journal
                Bioinformatics
                Bioinformatics
                bioinformatics
                Bioinformatics
                Oxford University Press
                1367-4803
                1367-4811
                February 2023
                20 January 2023
                20 January 2023
                : 39
                : 2
                : btad043
                Affiliations
                School of Computer Science and Technology, China University of Mining and Technology , Xuzhou 221116, China
                School of Computer Science and Technology, China University of Mining and Technology , Xuzhou 221116, China
                School of Computer Science, Northwestern Polytechnical University , Xi’an 710072, China
                Central Lab, Changzhi Medical College , Changzhi 046000, China
                School of Computer Science and Technology, China University of Mining and Technology , Xuzhou 221116, China
                Author notes
                Author information
                https://orcid.org/0000-0003-1644-1006
                Article
                btad043
                10.1093/bioinformatics/btad043
                9919433
                36661313
                03e2439d-4c00-4f46-942f-6d0a7fd3a675
                © The Author(s) 2023. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 October 2022
                : 30 December 2022
                : 09 January 2023
                : 19 January 2023
                : 11 February 2023
                Page count
                Pages: 7
                Funding
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 61972399
                Categories
                Original Paper
                Gene Expression
                AcademicSubjects/SCI01060

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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