D412–D416 Nucleic Acids Research, 2009, Vol. 37, Database issue doi:10.1093/nar/gkn760 Published online 21 October 2008 STRING 8—a global view on proteins and their functional interactions in 630 organisms Lars J. Jensen1,2, Michael Kuhn 1 , Manuel Stark3, Samuel Chaffron 3 , Chris Creevey1, Jean Muller1, Tobias Doerks1, Philippe Julien 4 , Alexander Roth3, Milan Simonovic3, Peer Bork1,5,* and Christian von Mering3 1European Molecular Biology Laboratory, Heidelberg, Germany, 2Novo Nordisk Foundation Centre for Protein Research, University of Copenhagen, Denmark, 3Institute of Molecular Biology and Swiss Institute of Bioinformatics, University of Zurich, 4Centre for Integrative Genomics, University of Lausanne, Switzerland and 5Max-Delbru¨ ck-Centre for Molecular Medicine, Berlin, Germany Received September 14, 2008; Accepted October 6, 2008 ABSTRACT Functional partnerships between proteins are at the core of complex cellular phenotypes, and the networks formed by interacting proteins provide researchers with crucial scaffolds for modeling, data reduction and annotation. STRING is a data- base and web resource dedicated to protein–protein interactions, including both physical and functional interactions. It weights and integrates information from numerous sources, including experimental repositories, computational prediction methods and public text collections, thus acting as a meta- database that maps all interaction evidence onto a common set of genomes and proteins. The most important new developments in STRING 8 over pre- vious releases include a URL-based programming interface, which can be used to query STRING from other resources, improved interaction predic- tion via genomic neighborhood in prokaryotes, and the inclusion of protein structures. Version 8.0 of STRING covers about 2.5 million proteins from 630 organisms, providing the most comprehensive view on protein–protein interactions currently available. STRING can be reached at http://string-db.org/. INTRODUCTION In contrast to genome sequences, which are quickly becoming a commodity, the functional connectivity within a proteome is a much more challenging problem. The various protein complexes, transient interactions and functional pathways are all context-dependent, and the experimental techniques for their elucidation are diverse, often not directly comparable, and less reliable than genome sequencing. Nevertheless, protein–protein interac- tion networks (or also ‘association networks’ in case func- tional associations are included) are a crucial ingredient for any system-level understanding of cellular machineries (1–5). Furthermore, protein networks can serve very con- crete, practical purposes such as ﬁltering and assessing high-throughput functional genomics data, and providing intuitive visual scaﬀolds for annotating the structural, functional and evolutionary properties of proteins. The database and web-tool STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) is a meta- resource that aggregates most of the available information on protein–protein associations, scores and weights it, and augments it with predicted interactions, as well as with the results of automatic literature-mining searches. Since its ﬁrst release in 2000 (6), it has grown into the most com- prehensive resource of its type. It builds upon and extends the excellent, manual annotation eﬀorts undertaken at primary protein interaction databases (7–12) and at data- bases of curated pathway knowledge (13–15). Here, we describe new features that have been added since our report on the previous release, STRING 7 (16). EXTENDING THE SOURCES OF INTERACTION INFORMATION The basic interaction unit in STRING is the ‘functional association’, which is deﬁned in this database as the spe- ciﬁc and meaningful interaction between two proteins that jointly contribute to the same functional process. With respect to the interacting proteins, STRING does not con- sider any speciﬁc splicing isoforms or posttranslational modiﬁcations, but instead represents each protein-coding *To whom correspondence should be addressed. Tel: +49 6221 3878526; Fax: +49 6221 387519; Email: bork@embl.de Correspondence may also be addressed to Christian von Mering. Tel: +41 44 6353147; Fax: +41 44 6356864; Email: mering@molbio.uzh.ch The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors. 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.