BioPAX (Biological Pathway Exchange) is a standard language to represent biological pathways at the molecular and cellular level. Its major use is to facilitate the exchange of pathway data (http://www.biopax.org). Pathway data captures our understanding of biological processes, but its rapid growth necessitates development of databases and computational tools to aid interpretation. However, the current fragmentation of pathway information across many databases with incompatible formats presents barriers to its effective use. BioPAX solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. BioPAX was created through a community process. Through BioPAX, millions of interactions organized into thousands of pathways across many organisms, from a growing number of sources, are available. Thus, large amounts of pathway data are available in a computable form to support visualization, analysis and biological discovery.

The Gene Ontology (GO) project (http://www.geneontology.org/) provides a set of structured, controlled vocabularies for community use in annotating genes, gene products and sequences (also see http://www.sequenceontology.org/). The ontologies have been extended and refined for several biological areas, and improvements to the structure of the ontologies have been implemented. To improve the quantity and quality of gene product annotations available from its public repository, the GO Consortium has launched a focused effort to provide comprehensive and detailed annotation of orthologous genes across a number of ‘reference’ genomes, including human and several key model organisms. Software developments include two releases of the ontology-editing tool OBO-Edit, and improvements to the AmiGO browser interface.

The Rat Genome Database (RGD, http://rgd.mcw.edu) provides the most comprehensive data repository and informatics platform related to the laboratory rat, one of the most important model organisms for disease studies. RGD maintains and updates datasets for genomic elements such as genes, transcripts and increasingly in recent years, sequence variations, as well as map positions for multiple assemblies and sequence information. Functional annotations for genomic elements are curated from published literature, submitted by researchers and integrated from other public resources. Complementing the genomic data catalogs are those associated with phenotypes and disease, including strains, QTL and experimental phenotype measurements across hundreds of strains. Data are submitted by researchers, acquired through bulk data pipelines or curated from published literature. Innovative software tools provide users with an integrated platform to query, mine, display and analyze valuable genomic and phenomic datasets for discovery and enhancement of their own research. This update highlights recent developments that reflect an increasing focus on: (i) genomic variation, (ii) phenotypes and diseases, (iii) data related to the environment and experimental conditions and (iv) datasets and software tools that allow the user to explore and analyze the interactions among these and their impact on disease.

A thermodynamic analysis of the binding of the TATA binding protein (TBP) from Saccharomyces cerevisiae to the adenovirus E4 promoter was conducted using quantitative DNase I "footprint" titration techniques. These studies were conducted to provide a foundation for studies of TBP structure-function relations and its assembly into transcription preinitiation complexes. The binding of TBP to the E4 promoter is well described by the Langmuir binding polynomial, suggesting that no linked equilibria contribute to the binding reaction under the conditions examined. Van't Hoff analysis yie1ded.a nonlinear dependence on temperature with the TBP-E4 promoter interaction displaying maximal affinity at 30 "C. An unusually negative value of the apparent standard heat capacity change, AC," = -3.5 f 0.5 kcal/mol*K, was determined from these data. The dependence of the TBP-E4 promoter interaction on [KCl] indicates that 3.6 & 0.3 K+ ions are displaced upon complex formation. Within experimental error, no linkage of proton binding with the TBP-E4 promoter interaction is detectable between pH 5.9 and 8.7. Rates of association of TBP for the E4 promoter were obtained using a novel implementation of a quench-flow device and DNase I "footprinting" techniques. The value determined for the second-order rate constant at pH 7.4, 100 mM KCI, 5 mM MgC12, 1 mM CaC12, 30 "C (k, = (5.2 f 0.5) x lo5 M-' s-') confirms the results obtained by Hawley and co-workers [Hoopes, B. C., LeBlanc, and extends them through TBP concentrations of 636 nM. The Arrhenius plot of the rate of TBP association is also nonlinear, yielding AC," = -3.2 & 0.3 kcal/mol*K. Thus, the AC," associated with the TBP-E4 promoter interaction appears associated principally, if not exclusively, with the rate-limiting step of binding. The consequences of these results for the interpretation of structural and biochemical studies of TBP-promoter complex formation are discussed.

The Gene Ontology (GO) is a collaborative effort that provides structured vocabularies for annotating the molecular function, biological role, and cellular location of gene products in a highly systematic way and in a species-neutral manner with the aim of unifying the representation of gene function across different organisms. Each contributing member of the GO Consortium independently associates GO terms to gene products from the organism(s) they are annotating. Here we introduce the Reference Genome project, which brings together those independent efforts into a unified framework based on the evolutionary relationships between genes in these different organisms. The Reference Genome project has two primary goals: to increase the depth and breadth of annotations for genes in each of the organisms in the project, and to create data sets and tools that enable other genome annotation efforts to infer GO annotations for homologous genes in their organisms. In addition, the project has several important incidental benefits, such as increasing annotation consistency across genome databases, and providing important improvements to the GO's logical structure and biological content.