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      Realistic in silico generation and augmentation of single-cell RNA-seq data using generative adversarial networks

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          Abstract

          A fundamental problem in biomedical research is the low number of observations available, mostly due to a lack of available biosamples, prohibitive costs, or ethical reasons. Augmenting few real observations with generated in silico samples could lead to more robust analysis results and a higher reproducibility rate. Here, we propose the use of conditional single-cell generative adversarial neural networks (cscGAN) for the realistic generation of single-cell RNA-seq data. cscGAN learns non-linear gene–gene dependencies from complex, multiple cell type samples and uses this information to generate realistic cells of defined types. Augmenting sparse cell populations with cscGAN generated cells improves downstream analyses such as the detection of marker genes, the robustness and reliability of classifiers, the assessment of novel analysis algorithms, and might reduce the number of animal experiments and costs in consequence. cscGAN outperforms existing methods for single-cell RNA-seq data generation in quality and hold great promise for the realistic generation and augmentation of other biomedical data types.

          Abstract

          Low sample numbers often limit the robustness of analyses in biomedical research. Here, the authors introduce a method to generate realistic scRNA-seq data using GANs that learn gene expression dependencies from complex samples, and show that augmenting spare cell populations improves downstream analyses.

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          Image-to-Image Translation with Conditional Adversarial Networks

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            PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells

            Single-cell RNA-seq quantifies biological heterogeneity across both discrete cell types and continuous cell transitions. Partition-based graph abstraction (PAGA) provides an interpretable graph-like map of the arising data manifold, based on estimating connectivity of manifold partitions (https://github.com/theislab/paga). PAGA maps preserve the global topology of data, allow analyzing data at different resolutions, and result in much higher computational efficiency of the typical exploratory data analysis workflow. We demonstrate the method by inferring structure-rich cell maps with consistent topology across four hematopoietic datasets, adult planaria and the zebrafish embryo and benchmark computational performance on one million neurons. Electronic supplementary material The online version of this article (10.1186/s13059-019-1663-x) contains supplementary material, which is available to authorized users.
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              Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq.

              Our understanding of the development and maintenance of tissues has been greatly aided by large-scale gene expression analysis. However, tissues are invariably complex, and expression analysis of a tissue confounds the true expression patterns of its constituent cell types. Here we describe a novel strategy to access such complex samples. Single-cell RNA-seq expression profiles were generated, and clustered to form a two-dimensional cell map onto which expression data were projected. The resulting cell map integrates three levels of organization: the whole population of cells, the functionally distinct subpopulations it contains, and the single cells themselves-all without need for known markers to classify cell types. The feasibility of the strategy was demonstrated by analyzing the transcriptomes of 85 single cells of two distinct types. We believe this strategy will enable the unbiased discovery and analysis of naturally occurring cell types during development, adult physiology, and disease.
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                Author and article information

                Contributors
                sbonn@uke.de
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                9 January 2020
                9 January 2020
                2020
                : 11
                : 166
                Affiliations
                [1 ]ISNI 0000 0001 2180 3484, GRID grid.13648.38, Institute of Medical Systems Biology, , University Medical Center Hamburg-Eppendorf, ; Hamburg, Germany
                [2 ]ISNI 0000 0001 2180 3484, GRID grid.13648.38, Center for Internal Medicine, III. Medical Clinic and Polyclinic, , University Medical Center Hamburg-Eppendorf, ; Hamburg, Germany
                [3 ]Genevention GmbH, Goettingen, Germany
                [4 ]ISNI 0000 0004 0438 0426, GRID grid.424247.3, German Center for Neurodegenerative Diseases, ; Tuebingen, Germany
                Author information
                http://orcid.org/0000-0002-2646-3674
                http://orcid.org/0000-0002-0944-7226
                http://orcid.org/0000-0003-0933-6152
                http://orcid.org/0000-0003-4366-5662
                Article
                14018
                10.1038/s41467-019-14018-z
                6952370
                31919373
                26c1cb0b-b5d5-40c4-94b9-2585abbb1d81
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 25 August 2018
                : 13 December 2019
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                © The Author(s) 2020

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                computational models,machine learning
                Uncategorized
                computational models, machine learning

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