Home LiteratureArticle Details
PMID: 27924014 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible.

Nucleic acids research ·Vol. 45 ·No. D1 ·2017-00-04 ·Pages D362-D368

Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Santos A, Doncheva NT, Roth A, Bork P, Jensen LJ, von Mering C

Abstract

A system-wide understanding of cellular function requires knowledge of all functional interactions between the expressed proteins. The STRING database aims to collect and integrate this information, by consolidating known and predicted protein-protein association data for a large number of organisms. The associations in STRING include direct (physical) interactions, as well as indirect (functional) interactions, as long as both are specific and biologically meaningful. Apart from collecting and reassessing available experimental data on protein-protein interactions, and importing known pathways and protein complexes from curated databases, interaction predictions are derived from the following sources: (i) systematic co-expression analysis, (ii) detection of shared selective signals across genomes, (iii) automated text-mining of the scientific literature and (iv) computational transfer of interaction knowledge between organisms based on gene orthology. In the latest version 10.5 of STRING, the biggest changes are concerned with data dissemination: the web frontend has been completely redesigned to reduce dependency on outdated browser technologies, and the database can now also be queried from inside the popular Cytoscape software framework. Further improvements include automated background analysis of user inputs for functional enrichments, and streamlined download options. The STRING resource is available online, at http://string-db.org/.

MeSH Terms
Computational Biology/methods Databases, Protein Models, Molecular Protein Binding Protein Conformation Protein Interaction Mapping Protein Interaction Maps Proteins/chemistry,metabolism Software Structure-Activity Relationship User-Computer Interface Web Browser
Chemicals
Proteins
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Szklarczyk Damian
Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zurich, 8057 Zurich, Switzerland.
Morris John H
Resource on Biocomputing, Visualization, and Informatics, University of California, San Francisco, CA 94158-2517, USA.
Cook Helen
Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen N, Denmark.
Kuhn Michael
Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Wyder Stefan
Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zurich, 8057 Zurich, Switzerland.
Simonovic Milan
Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zurich, 8057 Zurich, Switzerland.
Santos Alberto
Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen N, Denmark.
Doncheva Nadezhda T
Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen N, Denmark.
Roth Alexander
Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zurich, 8057 Zurich, Switzerland.
Bork Peer
Structural and Computational Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany [email protected]. | Molecular Medicine Partnership Unit, University of Heidelberg and European Molecular Biology Laboratory, 69117 Heidelberg, Germany. | Max Delbrück Centre for Molecular Medicine, 13125 Berlin, Germany. | Department of Bioinformatics, Biocenter, University of Würzburg, 97074 Würzburg, Germany.
Jensen Lars J
Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, 2200 Copenhagen N, Denmark [email protected].
von Mering Christian ORCID
Institute of Molecular Life Sciences and Swiss Institute of Bioinformatics, University of Zurich, 8057 Zurich, Switzerland [email protected].
References (55)
55 references, click to expand
  1. The identification of functional modules from the genomic association of genes.
    Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5890-5 PMID: 11983890
  2. Network-based in silico drug efficacy screening.
    Nat Commun. 2016 Feb 01;7:10331 PMID: 26831545
  3. Network.assisted analysis to prioritize GWAS results: principles, methods and perspectives.
    Hum Genet. 2014 Feb;133(2):125-38 PMID: 24122152
  4. STRING v9.1: protein-protein interaction networks, with increased coverage and integration.
    Nucleic Acids Res. 2013 Jan;41(Database issue):D808-15 PMID: 23203871
  5. The BioGRID interaction database: 2015 update.
    Nucleic Acids Res. 2015 Jan;43(Database issue):D470-8 PMID: 25428363
  6. Cytoscape: a software environment for integrated models of biomolecular interaction networks.
    Genome Res. 2003 Nov;13(11):2498-504 PMID: 14597658
  7. Functional associations of proteins in entire genomes by means of exhaustive detection of gene fusions.
    Genome Biol. 2001;2(9):RESEARCH0034 PMID: 11820254
  8. Biological network analysis with CentiScaPe: centralities and experimental dataset integration.
    F1000Res. 2014 Jul 01;3:139 PMID: 26594322
  9. UniProt: a hub for protein information.
    Nucleic Acids Res. 2015 Jan;43(Database issue):D204-12 PMID: 25348405
  10. Functional association networks as priors for gene regulatory network inference.
    Bioinformatics. 2014 Jun 15;30(12):i130-8 PMID: 24931976
  11. DISEASES: text mining and data integration of disease-gene associations.
    Methods. 2015 Mar;74:83-9 PMID: 25484339
  12. How many protein-protein interactions types exist in nature?
    PLoS One. 2012;7(6):e38913 PMID: 22719985
  13. Network-based stratification of tumor mutations.
    Nat Methods. 2013 Nov;10(11):1108-15 PMID: 24037242
  14. APID interactomes: providing proteome-based interactomes with controlled quality for multiple species and derived networks.
    Nucleic Acids Res. 2016 Jul 8;44(W1):W529-35 PMID: 27131791
  15. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks.
    Bioinformatics. 2009 Apr 15;25(8):1091-3 PMID: 19237447
  16. GeneMANIA prediction server 2013 update.
    Nucleic Acids Res. 2013 Jul;41(Web Server issue):W115-22 PMID: 23794635
  17. Selecting causal genes from genome-wide association studies via functionally coherent subnetworks.
    Nat Methods. 2015 Feb;12(2):154-9 PMID: 25532137
  18. STRING: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene.
    Nucleic Acids Res. 2000 Sep 15;28(18):3442-4 PMID: 10982861
  19. STRING v10: protein-protein interaction networks, integrated over the tree of life.
    Nucleic Acids Res. 2015 Jan;43(Database issue):D447-52 PMID: 25352553
  20. Integration of biological networks and gene expression data using Cytoscape.
    Nat Protoc. 2007;2(10):2366-82 PMID: 17947979
  21. Annotation transfer between genomes: protein-protein interologs and protein-DNA regulogs.
    Genome Res. 2004 Jun;14(6):1107-18 PMID: 15173116
  22. STAMS: STRING-assisted module search for genome wide association studies and application to autism.
    Bioinformatics. 2016 Dec 15;32(24):3815-3822 PMID: 27542772
  23. COMPARTMENTS: unification and visualization of protein subcellular localization evidence.
    Database (Oxford). 2014 Feb 25;2014:bau012 PMID: 24573882
  24. Genic insights from integrated human proteomics in GeneCards.
    Database (Oxford). 2016 Apr 05;2016: PMID: 27048349
  25. Modular organization of cellular networks.
    Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1128-33 PMID: 12538875
  26. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders.
    Nucleic Acids Res. 2015 Jan;43(Database issue):D789-98 PMID: 25428349
  27. The MIntAct project--IntAct as a common curation platform for 11 molecular interaction databases.
    Nucleic Acids Res. 2014 Jan;42(Database issue):D358-63 PMID: 24234451
  28. Combining guilt-by-association and guilt-by-profiling to predict Saccharomyces cerevisiae gene function.
    Genome Biol. 2008;9 Suppl 1:S7 PMID: 18613951
  29. Ten thousand interactions for the molecular biologist.
    Nat Biotechnol. 2004 Oct;22(10):1317-21 PMID: 15470473
  30. Genes2FANs: connecting genes through functional association networks.
    BMC Bioinformatics. 2012 Jul 02;13:156 PMID: 22748121
  31. Integrated interactions database: tissue-specific view of the human and model organism interactomes.
    Nucleic Acids Res. 2016 Jan 4;44(D1):D536-41 PMID: 26516188
  32. iRefWeb: interactive analysis of consolidated protein interaction data and their supporting evidence.
    Database (Oxford). 2010 Oct 12;2010:baq023 PMID: 20940177
  33. IMP 2.0: a multi-species functional genomics portal for integration, visualization and prediction of protein functions and networks.
    Nucleic Acids Res. 2015 Jul 1;43(W1):W128-33 PMID: 25969450
  34. clusterMaker: a multi-algorithm clustering plugin for Cytoscape.
    BMC Bioinformatics. 2011 Nov 09;12:436 PMID: 22070249
  35. Temporal proteomics of NGF-TrkA signaling identifies an inhibitory role for the E3 ligase Cbl-b in neuroblastoma cell differentiation.
    Sci Signal. 2015 Apr 28;8(374):ra40 PMID: 25921289
  36. SVD-phy: improved prediction of protein functional associations through singular value decomposition of phylogenetic profiles.
    Bioinformatics. 2016 Apr 1;32(7):1085-7 PMID: 26614125
  37. HINT: High-quality protein interactomes and their applications in understanding human disease.
    BMC Syst Biol. 2012 Jul 30;6:92 PMID: 22846459
  38. Saccharomyces Genome Database: the genomics resource of budding yeast.
    Nucleic Acids Res. 2012 Jan;40(Database issue):D700-5 PMID: 22110037
  39. Network analysis of GWAS data.
    Curr Opin Genet Dev. 2013 Dec;23(6):602-10 PMID: 24287332
  40. Protein interaction mapping in C. elegans using proteins involved in vulval development.
    Science. 2000 Jan 7;287(5450):116-22 PMID: 10615043
  41. Prioritizing candidate disease genes by network-based boosting of genome-wide association data.
    Genome Res. 2011 Jul;21(7):1109-21 PMID: 21536720
  42. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks.
    Bioinformatics. 2005 Aug 15;21(16):3448-9 PMID: 15972284
  43. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored.
    Nucleic Acids Res. 2011 Jan;39(Database issue):D561-8 PMID: 21045058
  44. Interactome data and databases: different types of protein interaction.
    Comp Funct Genomics. 2004;5(2):173-8 PMID: 18629062
  45. Human diseases through the lens of network biology.
    Trends Genet. 2013 Mar;29(3):150-9 PMID: 23219555
  46. Structural space of protein-protein interfaces is degenerate, close to complete, and highly connected.
    Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22517-22 PMID: 21149688
  47. A travel guide to Cytoscape plugins.
    Nat Methods. 2012 Nov;9(11):1069-76 PMID: 23132118
  48. Comprehensive comparison of large-scale tissue expression datasets.
    PeerJ. 2015 Jun 30;3:e1054 PMID: 26157623
  49. Network and data integration for biomarker signature discovery via network smoothed T-statistics.
    PLoS One. 2013 Sep 03;8(9):e73074 PMID: 24019896
  50. ALSoD: A user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics.
    Hum Mutat. 2012 Sep;33(9):1345-51 PMID: 22753137
  51. FunCoup 3.0: database of genome-wide functional coupling networks.
    Nucleic Acids Res. 2014 Jan;42(Database issue):D380-8 PMID: 24185702
  52. Enrichment or depletion of a GO category within a class of genes: which test?
    Bioinformatics. 2007 Feb 15;23(4):401-7 PMID: 17182697
  53. Protein interaction data curation: the International Molecular Exchange (IMEx) consortium.
    Nat Methods. 2012 Apr;9(4):345-50 PMID: 22453911
  54. eggNOG 4.5: a hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences.
    Nucleic Acids Res. 2016 Jan 4;44(D1):D286-93 PMID: 26582926
  55. STRING 8--a global view on proteins and their functional interactions in 630 organisms.
    Nucleic Acids Res. 2009 Jan;37(Database issue):D412-6 PMID: 18940858
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkw937
Email
[email protected]
[email protected]
[email protected]
Published
2017-00-04
Epub
2016-00-18
Pages
D362-D368
Language
English
Region
England
NLM ID
0411011
PMCID
PMC5210637
Subset
IM
Grants
NIGMS NIH HHS · P41 GM103311 · United States
NIGMS NIH HHS · P41 GM103504 · United States
External Links
PubMed source DOI: 10.1093/nar/gkw937 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2