Terms found in the source ontologies, which may be toggled on or off via the greyed-out Tools and Resources toolbar to the right of the page, are highlighted in different colours: e.g. pink highlights denote compound terms, which link out to diagrams of their structures, synonyms, Simplified Molecular Input Line Entry Specification (SMILES) nomenclature, etc.; yellow highlights link to definitions from the Gold Book; blue highlights are biomedical terms and green highlights are chemical terms, both of which link out to relevant definitions, synonyms and ontologies. Fragments of linked webpages are overlaid on this Figure as ‘callouts’. (http://www.rsc.org/Publishing/Journals/ProjectProspect/). The extract from Molecular BioSystems ([48]; Koenigs, M.B., Richardson, E.A. and Dube, D.H. (2009) Metabolic profiling of Helicobacter pylori glycosylation. Volume 5, 909–912; http://dx.doi.org/10.1039/b902178g) has been reproduced by permission of The Royal Society of Chemistry.

Two interactions are described, with relevant references to their MINT and UniProtKB entries.

Users may select from the coloured tabs at the top of the page to reveal entities of interest in the text: here, the protein (purple), disease (red), habitat (green) and organism (blue) tabs have been chosen. Organism terms are linked to uBio, a community initiative to create a comprehensive catalogue of the names of all (living and once-living) organisms (e.g. overlaid here as a ‘callout’). (http://www.ubio.org). Reproduced from [58]; Reis, R.B., Ribeiro, G.S., Felzemburgh, R.D., Santana, F.S., Mohr, S., Melendez, A.X., Queiroz, A., Santos, A.C., Ravines, R.R., Tassinari, W.S. et al. (2008) Impact of environment and social gradient on Leptospira infection in urban slums. PLoS Neglected Tropical Diseases 2, e228.

For readers viewing this article using UD, from this typical table of data from the European Journal of Pharmaceutical Sciences [62], explore the result of clicking on the UD logo. Reproduced from Corti, G., Maestrelli, F., Cirri, M., Zerrouk, N. and Mura, P. (2006) Development and evaluation of an in vitro method for prediction of human drug absorption II. Demonstration of the method suitability. European Journal of Pharmaceutical Science 27, 354–362, Copyright (2006) with permission from Elsevier.

In this 2008 Biophysical Chemistry article [66], Illingworth et al. describe the GXXG motifs characteristic of the LanC (lanthionine synthetase C)-like proteins (a), and also reference them elsewhere in the literature (b), including their appearance in nisin cyclase, whose three-dimensional structure was determined by Li et al. [67], and in the putative G protein-coupled receptor (GPCR) GCR2 [68] (c). For readers viewing this article using UD, to bring life to this image and visualize the GXXG motifs, click on the UD logo. Reproduced from Illingworth, C.J.R., Parkes, K.E., Snell, C.R., Mullineaux, P.M. and Reynolds, C.A (2008) Criteria for confirming sequence periodicity identified by Fourier transform analysis: application to GCR2, a candidate plant GPCR? Biophysical Chemistry 133, 28–35, Copyright (2008), with permission from Elsevier; and from Gao, Y., Zeng, Q., Guo, J., Cheng, J., Ellis, B. E. and Chen, J.-G. (2007) Genetic characterization reveals no role for the reported ABA receptor, GCR2, in ABA control of seed germination and early seedling development in Arabidopsis. The Plant Journal 52, 1001–1013 with permission from Wiley-Blackwell.

In 2007, Liu et al. [71] reported in Science the discovery of a novel plant G protein-coupled receptor (GPCR), so-called GCR2 (a). Much of the supporting evidence rested on a ‘characteristic’ hydropathy profile (reported as a Supplementary Figure), which showed seven peaks, apparently consistent with known GPCR transmembrane (TM) domain topology (b). Illingworth et al. challenged this result, pointing to the clear similarity of GCR2 with LanC-like proteins and showing that the topology of the hydropathy profile was the result of the seven-fold symmetry of the inner helical toroid (the blue/green region in the centre of the structure) of this globular protein (c) [66]. It is interesting to compare a hydropathy plot (d) with that reported by Liu et al. (b), generated using the same DAS TM prediction server [72] – note the omission of the significance bars in the latter, which in the former show that only one of the seven peaks scores above the significance threshold for TM domains and hence argues strongly against this being a membrane protein. Compare the structure of a bona fide GPCR [bovine rhodopsin, PDB code 1F88 (e)] with the nisin cyclase structure shown in Illingworth's paper [PDB code 2G0D (c)]. Despite the obvious lack of sequence and structural similarity of GCR2 to genuine GPCRs, and its clear affiliation with the LanC-like proteins, this error has been propagated to the description line of its UniProt entry, even though the entry contains database cross-references to LanC-like proteins rather than GPCRs (f). For readers viewing this article using UD, click on the UD logos in the Figure to explore this scenario further. Reproduced from Illingworth, C.J.R., Parkes, K.E., Snell, C.R., Mullineaux, P.M. and Reynolds, C.A (2008) Criteria for confirming sequence periodicity identified by Fourier transform analysis: application to GCR2, a candidate plant GPCR? Biophysical Chemistry 133, 28–35, Copyright (2008), with permission from Elsevier; and from Liu, X. G., Yue, Y. L., Li, B., Nie, Y. L., Li, W., Wu, W. H. and Ma, L. G. (2007) A G protein-coupled receptor is a plasma membrane receptor for the plant hormone abscisic acid. Science 315, 1712–1716 (http://www.sciencemag.org/cgi/content/abstract/315/5819/1712), with permission from AAAS.

GO terms are highlighted in a webpage; clicking on these reveals glossary information from GO; link targets to PubMed abstracts (such as the one here from Current Opinion in Plant Biology [45]) are provided by modifying the preferences to use an appropriate Google search. (http://cohse.cs.manchester.ac.uk/). The ‘Cellular Respiration’ panel is reproduced from Kimball's Biology Pages (http://biology-pages.info) with permission from Professor John W. Kimball. The PubMed record of Weber, A.P. (2004) Solute transporters as connecting elements between cytosol and plastid stroma. Current Opinion in Plant Biology 7, 247–253, has been reproduced with permission from the National Library of Medicine and Elsevier.

Marked-up chemical entities include chemical families, chemical names (pale orange highlights), chemical groups (dark green) and reaction types, with links out to Wikipedia where appropriate (e.g. overlaid here as a ‘callout’). Displayed mark-up is controlled via the Article Mark-up toolbar, shown on the right-hand side of the screen-shot. (http://www.chemmantis.com). The extract from The ChemSpider Journal of Chemistry ([49]; Walker, M.A. (2009) Some highlights in synthetic organic methodology, article 895), has been reproduced by permission of The Royal Society of Chemistry.

Terms found in the source ontologies are highlighted in different colours (blue, GO terms; pink, physicochemical methods and properties ontology; purple, physicochemical process ontology). PDB identifiers are underlined. Clicking on the marked-up entities invokes pop-up menus displaying term definitions, and sequence and structural details from the PDB, as appropriate. (http://biolit.ucsd.edu/doc/). Reproduced from [57]; Gu, J., Gribskov, M. and Bourne, P.E. (2006) Wiggle-predicting functionally flexible regions from primary sequence. PLoS Computational Biology 2, e90.

The text, from [59], shows tagged protein (blue) and chemical (gold) entities, and those for which both protein and chemical names are available (purple); clicking on a tagged entity invokes a pop-up summary, including links to features such as the structure of the protein (or chemical), its domain composition, its sequence, etc. The system is tuned for speed over accuracy, so users need to be aware of likely errors. (http://reflect.ws/).

In this 2009 BJ paper, Vandermarliere et al. [64] describe the catalytic site of Bacillus subtilis arabinoxylan arabinofuranohydrolase. The catalytic domain is shown in blue and the carbohydrate-binding module in green. For readers viewing this article using UD, explore further by clicking on the UD logo.

The colour overlay denotes the number of semantic relationships for particular areas (green areas having the least and red the most), illustrating the extent of the opportunities for mark-up that exist on a single page, and hence the need to balance both appropriate mark-up tools and appropriate levels of manual intervention to make this information usefully accessible to readers: mark-up too much information, and the reader is overwhelmed; mark-up too little, and the reader is denied access to the full semantic richness of the article. For readers viewing this article using UD, click on the UD logo.