STITCH: interaction networks of chemicals and proteins

Abstract

The knowledge about interactions between proteins and small molecules is essential for the understanding of molecular and cellular functions. However, information on such interactions is widely dispersed across numerous databases and the literature. To facilitate access to this data, STITCH ('search tool for interactions of chemicals') integrates information about interactions from metabolic pathways, crystal structures, binding experiments and drug-target relationships. Inferred information from phenotypic effects, text mining and chemical structure similarity is used to predict relations between chemicals. STITCH further allows exploring the network of chemical relations, also in the context of associated binding proteins. Each proposed interaction can be traced back to the original data sources. Our database contains interaction information for over 68,000 different chemicals, including 2200 drugs, and connects them to 1.5 million genes across 373 genomes and their interactions contained in the STRING database. STITCH is available at http://stitch.embl.de/.

Figure 1.

Interactions of the topoisomerase II inhibitor amsacrine. Chemicals are represented as pill-shaped nodes, while proteins are shown as spheres. Nodes that are associated to each other are linked by an edge: like mitoxantrone, amsacrine is known to bind (blue lines) and inhibit (red arrows) type II topoisomerases. Other compounds have similar activities as amsacrine or mitoxantrone in the NCI60 anti-cancer drug screens and are thus predicted to have the same mechanism of action (cyan lines).

Figure 2.

Network around acetylcholine and acetylcholinesterase (ACHE). (a) In confidence view, thicker lines represent stronger associations. (b) Lines and, for directed edges, arrows of different colours stand for different edge types in the actions view: binding (blue), activation (green), inhibition (red), catalysis (magenta), same activity (cyan) and reaction (black). The network shows the hydrolysis from acetylcholine to choline that is catalysed by ACHE. Several drugs, for example, the nootropic drug donepezil, inhibit ACHE.