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      SingleCellSignalR: inference of intercellular networks from single-cell transcriptomics

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          Abstract

          Single-cell transcriptomics offers unprecedented opportunities to infer the ligand–receptor (LR) interactions underlying cellular networks. We introduce a new, curated LR database and a novel regularized score to perform such inferences. For the first time, we try to assess the confidence in predicted LR interactions and show that our regularized score outperforms other scoring schemes while controlling false positives. SingleCellSignalR is implemented as an open-access R package accessible to entry-level users and available from https://github.com/SCA-IRCM. Analysis results come in a variety of tabular and graphical formats. For instance, we provide a unique network view integrating all the intercellular interactions, and a function relating receptors to expressed intracellular pathways. A detailed comparison of related tools is conducted. Among various examples, we demonstrate SingleCellSignalR on mouse epidermis data and discover an oriented communication structure from external to basal layers.

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          Most cited references24

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          The canonical Notch signaling pathway: unfolding the activation mechanism.

          Notch signaling regulates many aspects of metazoan development and tissue renewal. Accordingly, the misregulation or loss of Notch signaling underlies a wide range of human disorders, from developmental syndromes to adult-onset diseases and cancer. Notch signaling is remarkably robust in most tissues even though each Notch molecule is irreversibly activated by proteolysis and signals only once without amplification by secondary messenger cascades. In this Review, we highlight recent studies in Notch signaling that reveal new molecular details about the regulation of ligand-mediated receptor activation, receptor proteolysis, and target selection.
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            The Universal Protein Resource (UniProt): an expanding universe of protein information

            The Universal Protein Resource (UniProt) provides a central resource on protein sequences and functional annotation with three database components, each addressing a key need in protein bioinformatics. The UniProt Knowledgebase (UniProtKB), comprising the manually annotated UniProtKB/Swiss-Prot section and the automatically annotated UniProtKB/TrEMBL section, is the preeminent storehouse of protein annotation. The extensive cross-references, functional and feature annotations and literature-based evidence attribution enable scientists to analyse proteins and query across databases. The UniProt Reference Clusters (UniRef) speed similarity searches via sequence space compression by merging sequences that are 100% (UniRef100), 90% (UniRef90) or 50% (UniRef50) identical. Finally, the UniProt Archive (UniParc) stores all publicly available protein sequences, containing the history of sequence data with links to the source databases. UniProt databases continue to grow in size and in availability of information. Recent and upcoming changes to database contents, formats, controlled vocabularies and services are described. New download availability includes all major releases of UniProtKB, sequence collections by taxonomic division and complete proteomes. A bibliography mapping service has been added, and an ID mapping service will be available soon. UniProt databases can be accessed online at or downloaded at .
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              PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data

              Abstract Single-cell RNA sequencing is an increasingly used method to measure gene expression at the single cell level and build cell-type atlases of tissues. Hundreds of single-cell sequencing datasets have already been published. However, studies are frequently deposited as raw data, a format difficult to access for biological researchers due to the need for data processing using complex computational pipelines. We have implemented an online database, PanglaoDB, accessible through a user-friendly interface that can be used to explore published mouse and human single cell RNA sequencing studies. PanglaoDB contains pre-processed and pre-computed analyses from more than 1054 single-cell experiments covering most major single cell platforms and protocols, based on more than 4 million cells from a wide range of tissues and organs. The online interface allows users to query and explore cell types, genetic pathways and regulatory networks. In addition, we have established a community-curated cell-type marker compendium, containing more than 6000 gene-cell-type associations, as a resource for automatic annotation of cell types.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                04 June 2020
                20 March 2020
                20 March 2020
                : 48
                : 10
                : e55
                Affiliations
                [1 ] Institut de Recherche en Cancérologie de Montpellier , Inserm, F-34298 Montpellier, France
                [2 ] Institut régional du Cancer Montpellier , F-34298 Montpellier, France
                [3 ] Université de Montpellier , F-34090 Montpellier, France
                [4 ] Département d’Hématologie Biologique, CHU Montpellier , Hôpital Saint Eloi, F-34090 Montpellier, France
                Author notes
                To whom correspondence should be addressed. Tel: +33 467 612 392; Fax: +33 467 613 787; Email: jacques.colinge@ 123456inserm.fr
                Author information
                http://orcid.org/0000-0002-2904-7430
                http://orcid.org/0000-0002-1268-9058
                Article
                gkaa183
                10.1093/nar/gkaa183
                7261168
                32196115
                d544f5e1-70e0-4ad1-9c02-d4fa3e089b96
                © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

                History
                : 10 March 2020
                : 23 January 2020
                : 12 December 2019
                Page count
                Pages: 12
                Funding
                Funded by: Labex EpiGenMed Postdoctoral Fellowship;
                Award ID: ANR-10-LABX-12-01
                Funded by: Fondation ARC pour la Recherche sur le Cancer, DOI 10.13039/501100004097;
                Award ID: PJA 20141201975
                Categories
                AcademicSubjects/SCI00010
                Narese/7
                Narese/24
                Methods Online

                Genetics
                Genetics

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