Nucleic Acids Research, 2009, Vol. 37, Database issue D415 Figure 3. The new Application Programming Interface, and how it connects to Cytoscape. Speciﬁc items of interest can be retrieved from STRING by constructing URLs accordingly (see Table). Unless STRING’s internal identiﬁers are known, an initial call with the ‘resolve’-request is recom- mended, to map query items to nodes in the STRING network. TSV, tab-separated values; JSON, JavaScript Object Notation; PSI-MI 2.5, Proteomics Standards Initiative Molecular Interaction (XML and tab-delimited format). Requests ending on ‘List’ accept more than one input item, but are otherwise identical (multiple query items must be separated by URL-encoded ‘new-line’ characters). installation of the complete relational database back-end (some of the downloads do require a free, nonredistribu- tion license applicable to academic nonproﬁt users). The interacting entities in STRING can be set to be either proteins, or groups of orthologs spanning multiple organ- isms (‘COG-mode’). For the latter, STRING relies on an updated and extended version of the COGs [‘Clusters of Orthologous Groups’ (29)], which is being maintained at the eggNOG database (30). A variety of other databases use STRING networks as a basis for further computa- tions/annotations, for example by augmenting the net- works with small molecules [STITCH, (31)], or by using the network to increase the power of kinase–substrate pre- dictions [NetworKIN, (32)]. STRING has also been inte- grated into third-party tools such as NeAT [Network Analysis Tools, (33)], which provides various ways to analyze the interaction network, or Gaggle (34), which enables automated data transfer into other tools via a browser add-on. ACKNOWLEDGEMENTS The authors wish to thank Dianna Fisk from the Saccharomyces Genome Database, and Thomas B. Brody from The Interactive Fly, for access to gene summary paragraphs. Code development was partially conducted at the ‘WebService BioHackathon 2008’ in Tokyo, Japan. FUNDING Swiss Institute of Bioinformatics; University of Zurich through its Research Priority Program ‘Systems Biology and Functional Genomics’; European Commission’s FP6 Programme through the ADIT Integrated Project (LSHB- CT-2005-511065); BioSapiens Network (LSHG-CT-2003-503265). Funding for charge: University of Zurich. of Excellence open access REFERENCES 1. Bader,S., Kuhner,S. and Gavin,A.C. (2008) Interaction networks for systems biology. FEBS Lett., 582, 1220–1224. 2. Devos,D. and Russell,R.B. (2007) A more complete, complexed and structured interactome. Curr. Opin. Struct. Biol., 17, 370–377. 3. Hu,Z., Mellor,J., Wu,J., Kanehisa,M., Stuart,J.M. and DeLisi,C. (2007) Towards zoomable multidimensional maps of the cell. Nat. Biotechnol., 25, 547–554. 4. Christensen,C., Thakar,J. and Albert,R. (2007) Systems-level insights into cellular regulation: inferring, analysing, and modelling intracellular networks. IET Syst. Biol., 1, 61–77. 5. Kohler,S., Bauer,S., Horn,D. and Robinson,P.N. (2008) Walking the interactome for prioritization of candidate disease genes. Am. J. Hum. Genet., 82, 949–958. 6. Snel,B., Lehmann,G., Bork,P. and Huynen,M.A. (2000) STRING: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Res., 28, 3442–3444. 7. Kerrien,S., Alam-Faruque,Y., Aranda,B., Bancarz,I., Bridge,A., Derow,C., Dimmer,E., Feuermann,M., Friedrichsen,A., Huntley,R. et al. (2007) IntAct—open source resource for molecular interaction data. Nucleic Acids Res., 35, D561–D565. 8. Breitkreutz,B.J., Stark,C., Reguly,T., Boucher,L., Breitkreutz,A., Livstone,M., Oughtred,R., Lackner,D.H., Bahler,J., Wood,V. et al. (2008) The BioGRID Interaction Database: 2008 update. Nucleic Acids Res., 36, D637–D640. 9. Mishra,G.R., Suresh,M., Kumaran,K., Kannabiran,N., Suresh,S., Bala,P., Shivakumar,K., Anuradha,N., Reddy,R., Raghavan,T.M. et al. (2006) Human protein reference database—2006 update. Nucleic Acids Res., 34, D411–D414. 10. Chatr-aryamontri,A., Ceol,A., Palazzi,L.M., Nardelli,G., Schneider,M.V., Castagnoli,L. and Cesareni,G. (2007) MINT: the Molecular INTeraction database. Nucleic Acids Res., 35, D572–D574. 11. Salwinski,L., Miller,C.S., Smith,A.J., Pettit,F.K., Bowie,J.U. and Eisenberg,D. (2004) The Database of Interacting Proteins: 2004 update. Nucleic Acids Res., 32, D449–D451.