D414 Nucleic Acids Research, 2009, Vol. 37, Database issue Figure 1. Protein association network in STRING. An example of the network view in STRING, centered on the query protein ‘hisB’ from Escherichia coli. The inset shows the annotations and options that are available for each protein, including references to other databases. Three ‘functional modules’ can readily be seen in the network, forming tightly connected clusters. These encompass histidine biosynthesis, branched-chain amino acid biosynthesis, and—less strongly connected—a part of fatty acid biosynthesis. Line color indicates the type of the supporting evidence; all underlying evidence can be inspected in dedicated viewers that are accessible from the network. Figure 2. Extended deﬁnition of genomic neighborhood. (A) Illustration of a conserved gene neighborhood, containing genes related to the biosynthesis and consumption of tryptophan (simpliﬁed from a STRING screenshot). Genes connected by lines are direct neighbors on the chromosome, and genes with similar colors are orthologs across the various organisms. The arrow marks a switch in gene orientation, leading to a head-to-head orientation of two presumptive operons. (B) Divergently oriented genes predict functional linkage in prokaryotes. Each dot sum- marizes a group (bin) of gene pairs with similar intergenic distances. The fraction of such pairs where both genes are annotated in the same KEGG pathway is indicated, implying functional partnership. Note that divergent gene pairs are slightly shifted towards larger intergenic distances, presumably to accommodate promoters and regulatory sequences. envision that the STRING API will be useful to devel- opers of web services, who plan to make use of the STRING interaction network. If a particular web service needs access to the complete set of interactions, it may still be advisable to maintain a local copy of our data distribu- tion. However, if the service requires access to many dif- ferent subsets (depending on user input), querying STRING via its API could reduce administrative load. The API is called by constructing a URL that contains the type of the request, the desired output format and the input items. The STRING server then returns the result of the computation in the desired format. Further documen- tation can be accessed via the STRING homepage. USE SCENARIOS Apart from the ad hoc and barrier-free access through the website, STRING can be downloaded and used locally, either in the form of concise ﬂat-ﬁles or as a mirror