Cytoscape stringApp: Network analysis and visualization of proteomics data

Protein networks have become a popular tool for analyzing and visualizing the often long lists of proteins or genes obtained from proteomics and other high-throughput technologies. One of the most popular sources of such networks is the STRING database, which provides protein networks for more than 2000 organisms, including both physical interactions from experimental data and functional associations from curated pathways, automatic text mining, and prediction methods. However, its web interface is mainly intended for inspection of small networks and their underlying evidence. The Cytoscape software, on the other hand, is much better suited for working with large networks and offers greater flexibility in terms of network analysis, import, and visualization of additional data. To include both resources in the same workflow, we created stringApp, a Cytoscape app that makes it easy to import STRING networks into Cytoscape, retains the appearance and many of the features of STRING, and integrates data from associated databases. Here, we introduce many of the stringApp features and show how they can be used to carry out complex network analysis and visualization tasks on a typical proteomics data set, all through the Cytoscape user interface. stringApp is freely available from the Cytoscape app store: http://apps.cytoscape.org/apps/stringapp .

[1]  David J. Galas,et al.  RCytoscape: tools for exploratory network analysis , 2013, BMC Bioinformatics.

[2]  Janos X. Binder,et al.  DISEASES: Text mining and data integration of disease–gene associations , 2014, bioRxiv.

[3]  S. Brunak,et al.  Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer , 2017, Cell reports.

[4]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[5]  Damian Szklarczyk,et al.  STITCH 5: augmenting protein–chemical interaction networks with tissue and affinity data , 2015, Nucleic Acids Res..

[6]  U. Hobohm,et al.  Selection of representative protein data sets , 1992, Protein science : a publication of the Protein Society.

[7]  Allan Kuchinsky,et al.  enhancedGraphics: a Cytoscape app for enhanced node graphics , 2014, F1000Research.

[8]  Jan Gorodkin,et al.  TISSUES 2.0: an integrative web resource on mammalian tissue expression , 2018, Database J. Biol. Databases Curation.

[9]  D. Krackhardt,et al.  Visualizing Complexity in Networks : Seeing Both the Forest and the Trees , 2003 .

[10]  A. Kornblihtt,et al.  The carboxy terminal domain of RNA polymerase II and alternative splicing. , 2010, Trends in biochemical sciences.

[11]  Laurence A. Brown,et al.  Meta-analysis of transcriptomic datasets identifies genes enriched in the mammalian circadian pacemaker , 2017, Nucleic acids research.

[12]  Cathy H. Wu,et al.  UniProt: the Universal Protein knowledgebase , 2004, Nucleic Acids Res..

[13]  Lizhen Shi,et al.  Construction and Optimization of a Large Gene Coexpression Network in Maize Using RNA-Seq Data1[OPEN] , 2017, Plant Physiology.

[14]  Aidan P. Tay,et al.  PTMOracle: A Cytoscape App for Covisualizing and Coanalyzing Post-Translational Modifications in Protein Interaction Networks. , 2017, Journal of proteome research.

[15]  Damian Szklarczyk,et al.  The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible , 2016, Nucleic Acids Res..

[16]  Rajarshi Guha,et al.  Pharos: Collating protein information to shed light on the druggable genome , 2016, Nucleic Acids Res..

[17]  Anton J. Enright,et al.  An efficient algorithm for large-scale detection of protein families. , 2002, Nucleic acids research.

[18]  Gary D. Bader,et al.  clusterMaker: a multi-algorithm clustering plugin for Cytoscape , 2011, BMC Bioinformatics.

[19]  Christian Stolte,et al.  COMPARTMENTS: unification and visualization of protein subcellular localization evidence , 2014, Database J. Biol. Databases Curation.

[20]  Tsippi Iny Stein,et al.  The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses , 2016, Current protocols in bioinformatics.

[21]  Cynthia A. Brewer,et al.  ColorBrewer.org: An Online Tool for Selecting Colour Schemes for Maps , 2003 .

[22]  Paul Shannon,et al.  CyREST: Turbocharging Cytoscape Access for External Tools via a RESTful API , 2015, F1000Research.

[23]  Michael L. Creech,et al.  Integration of biological networks and gene expression data using Cytoscape , 2007, Nature Protocols.