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      DeepImpute: an accurate, fast, and scalable deep neural network method to impute single-cell RNA-seq data

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          Abstract

          Single-cell RNA sequencing (scRNA-seq) offers new opportunities to study gene expression of tens of thousands of single cells simultaneously. We present DeepImpute, a deep neural network-based imputation algorithm that uses dropout layers and loss functions to learn patterns in the data, allowing for accurate imputation. Overall, DeepImpute yields better accuracy than other six publicly available scRNA-seq imputation methods on experimental data, as measured by the mean squared error or Pearson’s correlation coefficient. DeepImpute is an accurate, fast, and scalable imputation tool that is suited to handle the ever-increasing volume of scRNA-seq data, and is freely available at https://github.com/lanagarmire/DeepImpute.

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          Most cited references27

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          From Louvain to Leiden: guaranteeing well-connected communities

          Community detection is often used to understand the structure of large and complex networks. One of the most popular algorithms for uncovering community structure is the so-called Louvain algorithm. We show that this algorithm has a major defect that largely went unnoticed until now: the Louvain algorithm may yield arbitrarily badly connected communities. In the worst case, communities may even be disconnected, especially when running the algorithm iteratively. In our experimental analysis, we observe that up to 25% of the communities are badly connected and up to 16% are disconnected. To address this problem, we introduce the Leiden algorithm. We prove that the Leiden algorithm yields communities that are guaranteed to be connected. In addition, we prove that, when the Leiden algorithm is applied iteratively, it converges to a partition in which all subsets of all communities are locally optimally assigned. Furthermore, by relying on a fast local move approach, the Leiden algorithm runs faster than the Louvain algorithm. We demonstrate the performance of the Leiden algorithm for several benchmark and real-world networks. We find that the Leiden algorithm is faster than the Louvain algorithm and uncovers better partitions, in addition to providing explicit guarantees.
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            Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells

            Recent molecular studies have revealed that, even when derived from a seemingly homogenous population, individual cells can exhibit substantial differences in gene expression, protein levels, and phenotypic output 1–5 , with important functional consequences 4,5 . Existing studies of cellular heterogeneity, however, have typically measured only a few pre-selected RNAs 1,2 or proteins 5,6 simultaneously because genomic profiling methods 3 could not be applied to single cells until very recently 7–10 . Here, we use single-cell RNA-Seq to investigate heterogeneity in the response of bone marrow derived dendritic cells (BMDCs) to lipopolysaccharide (LPS). We find extensive, and previously unobserved, bimodal variation in mRNA abundance and splicing patterns, which we validate by RNA-fluorescence in situ hybridization (RNA-FISH) for select transcripts. In particular, hundreds of key immune genes are bimodally expressed across cells, surprisingly even for genes that are very highly expressed at the population average. Moreover, splicing patterns demonstrate previously unobserved levels of heterogeneity between cells. Some of the observed bimodality can be attributed to closely related, yet distinct, known maturity states of BMDCs; other portions reflect differences in the usage of key regulatory circuits. For example, we identify a module of 137 highly variable, yet co-regulated, antiviral response genes. Using cells from knockout mice, we show that variability in this module may be propagated through an interferon feedback circuit involving the transcriptional regulators Stat2 and Irf7. Our study demonstrates the power and promise of single-cell genomics in uncovering functional diversity between cells and in deciphering cell states and circuits.
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              The technology and biology of single-cell RNA sequencing.

              The differences between individual cells can have profound functional consequences, in both unicellular and multicellular organisms. Recently developed single-cell mRNA-sequencing methods enable unbiased, high-throughput, and high-resolution transcriptomic analysis of individual cells. This provides an additional dimension to transcriptomic information relative to traditional methods that profile bulk populations of cells. Already, single-cell RNA-sequencing methods have revealed new biology in terms of the composition of tissues, the dynamics of transcription, and the regulatory relationships between genes. Rapid technological developments at the level of cell capture, phenotyping, molecular biology, and bioinformatics promise an exciting future with numerous biological and medical applications.
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                Author and article information

                Contributors
                lgarmire@med.umich.edu
                Journal
                Genome Biol
                Genome Biol
                Genome Biology
                BioMed Central (London )
                1474-7596
                1474-760X
                18 October 2019
                18 October 2019
                2019
                : 20
                : 211
                Affiliations
                [1 ]ISNI 0000 0001 2188 0957, GRID grid.410445.0, Department of Information and Computer Science, , University of Hawaii at Manoa, ; Honolulu, HI 96816 USA
                [2 ]ISNI 0000 0001 2188 0957, GRID grid.410445.0, Department of Epidemiology, , University of Hawaii Cancer Center, ; 701 Ilalo Street, Honolulu, HI 96813 USA
                [3 ]ISNI 0000 0001 2188 0957, GRID grid.410445.0, Department of Molecular Biology and Bioengineering, , University of Hawaii at Manoa, ; Honolulu, HI 96816 USA
                [4 ]ISNI 0000000086837370, GRID grid.214458.e, Department of Computational Medicine and Bioinformatics, , University of Michigan, ; Ann Arbor, MI 48105 USA
                Author information
                http://orcid.org/0000-0002-4654-2126
                Article
                1837
                10.1186/s13059-019-1837-6
                6798445
                31627739
                8b3b8109-28b1-4919-a8ac-6f48d3d58eab
                © The Author(s). 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 July 2019
                : 26 September 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: K01ES025434
                Award ID: R01 LM012373
                Award ID: R01 HD084633
                Categories
                Method
                Custom metadata
                © The Author(s) 2019

                Genetics
                rna-seq,single-cell,imputation,deep learning,machine learning,neural network,dropout,deepimpute
                Genetics
                rna-seq, single-cell, imputation, deep learning, machine learning, neural network, dropout, deepimpute

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