The Genom of Homo sapiens.pdf

238 JOSHI-TOPE ET AL.Figure 1. The GK front page.tial release date and possibly a more recent revision date.These features allow the module to be cited like a publication.Figure 2 shows what the user sees as he moves downfollowing a pathway, in this case a step in the G 1 phase ofthe mitotic cell cycle. The navigation bar on the leftshows an expandable outline of the current pathway,keeping track of the context of the current step in the contextof the larger pathway. The detail panel on the rightfeatures a human-readable summary of the step, an optionaldiagram, and a summary of all complexes, proteinproducts, and other macromolecules that participate inthis step. The detail panel also lists orthologous reactionsthat occur or are predicted to occur in other model organisms/species, and literature citations directly relevant tothe step. (The citations and orthologous reactions arescrolled out of view in Fig. 2.) All gene product namescurrently link out to SwissProt. Links to EnsEMBL, Ref-Seq, and model organism databases will be phased in duringthe autumn of 2003/winter of 2004.Naturally, pathways do not stand alone but are interconnected.When a user is viewing the details of a molecularreaction that participates in multiple pathways, thenavigation bar at the left expands to show him each of thepathways that the reaction participates in.The bioinformaticists’ view of GK, using an experimental“pathfinder” viewer, is shown in Figure 3. Herewe have just executed a query to find the shortest path betweenD-fructose and pyruvate. GK finds a path throughthe reactions that define intermediate metabolism anddisplays them in an interactive format. Although this representationis easiest to understand in the context of classicalbiochemical pathways, it can be used to explore anybiological process; for example, to find the steps that connecta primary RNA transcript located in the nucleus to acapped, spliced, polyadenylated messenger RNA locatedin the cytoplasm.From the bioinformaticist’s point of view, GK is adatabase that organizes proteins and other macromoleculesinto reactions and organizes these in turn intopathways. This information is invaluable when searchingfor the biological signatures hidden in large-scale datasets such as microarray expression studies and proteininteractionscreens.THE GK MISSIONGK’s central mission is to provide a nexus for connectingthe online gene-centric databases to the researchliterature through sets of curated reactions and pathways.Since this is a monumental task, we have limited thescope of our work in the following ways:• The focus of GK is on biological pathways that arethought to operate in humans. Photosynthesis, theyeast mating type switch, and the iron/sulfur biochemistryof the inhabitants of thermal vents can all besafely ignored.• GK deliberately avoids “cutting edge” research. Weask our authors to stay about a year behind the current