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      IntAct App: a Cytoscape application for molecular interaction network visualization and analysis

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          Abstract

          Summary

          IntAct App is a Cytoscape 3 application that grants in-depth access to IntAct’s molecular interaction data. It build networks where nodes are interacting molecules (mainly proteins, but also genes, RNA, chemicals…) and edges represent evidence of interaction. Users can query a network by providing its molecules, identified by different fields and optionally include all their interacting partners in the resulting network. The app offers three visualizations: one only displaying interactions, another representing every evidence and the last one emphasizing evidence where mutated versions of proteins were used. Users can also filter networks and click on nodes and edges to access all their related details. Finally, the application supports automation of its main features via Cytoscape commands.

          Availability and implementation

          Implementation available at https://apps.cytoscape.org/apps/intactapp, while the source code is available at https://github.com/EBI-IntAct/IntactApp.

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          Most cited references8

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          Cytoscape: a software environment for integrated models of biomolecular interaction networks.

          Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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              The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases

              IntAct (freely available at http://www.ebi.ac.uk/intact) is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. IntAct has developed a sophisticated web-based curation tool, capable of supporting both IMEx- and MIMIx-level curation. This tool is now utilized by multiple additional curation teams, all of whom annotate data directly into the IntAct database. Members of the IntAct team supply appropriate levels of training, perform quality control on entries and take responsibility for long-term data maintenance. Recently, the MINT and IntAct databases decided to merge their separate efforts to make optimal use of limited developer resources and maximize the curation output. All data manually curated by the MINT curators have been moved into the IntAct database at EMBL-EBI and are merged with the existing IntAct dataset. Both IntAct and MINT are active contributors to the IMEx consortium (http://www.imexconsortium.org).
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                Author and article information

                Contributors
                Role: Associate Editor
                Journal
                Bioinformatics
                Bioinformatics
                bioinformatics
                Bioinformatics
                Oxford University Press
                1367-4803
                1367-4811
                15 October 2021
                07 May 2021
                07 May 2021
                : 37
                : 20
                : 3684-3685
                Affiliations
                [1 ] European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Genome Campus,  Hinxton, Cambridgeshire CB10 1SD, UK
                [2 ] Resource for Biocomputing, Visualization, and Informatics, Department of Pharmaceutical Chemistry, University of California , San Francisco, CA 94158 2517, USA
                Author notes
                To whom correspondence should be addressed. hhe@ 123456ebi.ac.uk or pporras@ 123456ebi.ac.uk
                Author information
                https://orcid.org/0000-0002-7876-6503
                Article
                btab319
                10.1093/bioinformatics/btab319
                8545338
                33961020
                579d348a-941d-422c-bf66-53295bf6fe2e
                © The Author(s) 2021. 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
                : 28 January 2021
                : 08 April 2021
                : 24 April 2021
                : 27 April 2021
                Page count
                Pages: 2
                Funding
                Funded by: EMBL core funding;
                Award ID: OTAR-044
                Award ID: OTAR02-048
                Funded by: Wellcome Trust, DOI 10.13039/100010269;
                Award ID: #3367
                Funded by: NIGMS, DOI 10.13039/100000057;
                Award ID: P41 GM103504
                Categories
                Applications Notes
                Systems Biology
                AcademicSubjects/SCI01060

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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