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Abstract Web services have become a key technology for bioinformatics, since life science databases are globally decentralized and the exponential increase in the amount of available data demands for efficient systems without the need to transfer entire databases for every step of an analysis. However, various incompatibilities among database resources and analysis services make it difficult to connect and integrate these into interoperable workflows. To resolve this situation, we invited domain specialists from web service providers, client software developers, Open Bio* projects, the BioMoby project and researchers of emerging areas where a standard exchange data format is not well established, for an intensive collaboration entitled the BioHackathon 2008. The meeting was hosted by the Database Center for Life Science (DBCLS) and Computational Biology Research Center (CBRC) and was held in Tokyo from February 11th to 15th, 2008. In this report we highlight the work accomplished and the common issues arisen from this event, including the standardization of data exchange formats and services in the emerging fields of glycoinformatics, biological interaction networks, text mining, and phyloinformatics. In addition, common shared object development based on BioSQL, as well as technical challenges in large data management, asynchronous services, and security are discussed. Consequently, we improved interoperability of web services in several fields, however, further cooperation among major database centers and continued collaborative efforts between service providers and software developers are still necessary for an effective advance in bioinformatics web service technologies.

Metagenomics-based functional profiling analysis is an effective means of gaining deeper insight into the composition of marine microbial populations and developing a better understanding of the interplay between the functional genome content of microbial communities and abiotic factors. Here we present a comprehensive analysis of 24 datasets covering surface and depth-related environments at 11 sites around the world's oceans. The complete datasets comprises approximately 12 million sequences, totaling 5,358 Mb. Based on profiling patterns of Clusters of Orthologous Groups (COGs) of proteins, a core set of reference photic and aphotic depth-related COGs, and a collection of COGs that are associated with extreme oxygen limitation were defined. Their inferred functions were utilized as indicators to characterize the distribution of light- and oxygen-related biological activities in marine environments. The results reveal that, while light level in the water column is a major determinant of phenotypic adaptation in marine microorganisms, oxygen concentration in the aphotic zone has a significant impact only in extremely hypoxic waters. Phylogenetic profiling of the reference photic/aphotic gene sets revealed a greater variety of source organisms in the aphotic zone, although the majority of individual photic and aphotic depth-related COGs are assigned to the same taxa across the different sites. This increase in phylogenetic and functional diversity of the core aphotic related COGs most probably reflects selection for the utilization of a broad range of alternate energy sources in the absence of light.

Torrents of genotype-phenotype data are being generated, all of which must be captured, processed, integrated, and exploited. To do this optimally requires the use of standard and interoperable "object models," providing a description of how to partition the total spectrum of information being dealt with into elemental "objects" (such as "alleles," "genotypes," "phenotype values," "methods") with precisely stated logical interrelationships (such as "A objects are made up from one or more B objects"). We herein propose the Phenotype and Genotype Experiment Object Model (PaGE-OM; www.pageom.org), which has been tested and implemented in conjunction with several major databases, and approved as a standard by the Object Management Group (OMG). PaGE-OM is open-source, ready for use by the wider community, and can be further developed as needs arise. It will help to improve information management, assist data integration, and simplify the task of informatics resource design and construction for genotype and phenotype data projects.

Ensembl (http://www.ensembl.org/) is a bioinformatics project to organize biological information around the sequences of large genomes. It is a comprehensive source of stable automatic annotation of individual genomes, and of the synteny and orthology relationships between them. It is also a framework for integration of any biological data that can be mapped onto features derived from the genomic sequence. Ensembl is available as an interactive Web site, a set of flat files, and as a complete, portable open source software system for handling genomes. All data are provided without restriction, and code is freely available. Ensembl's aims are to continue to "widen" this biological integration to include other model organisms relevant to understanding human biology as they become available; to "deepen" this integration to provide an ever more seamless linkage between equivalent components in different species; and to provide further classification of functional elements in the genome that have been previously elusive.

Two clones of NIH3T3 fibroblasts, NEN37 and NEN7, overexpressing chimeric EGF/neu receptors (3 x 10(5) and 1 x 10(6) receptors/cell, respectively), were treated with EGF in order to identify the array of intracellular signals generated after activation of the neu proto-oncogene product. The results thus obtained were correlated with the effects of EGF on cell growth, investigated by both [3H]thymidine incorporation and long term (5 days) proliferation studies. In addition to the stimulation of the neu tyrosine kinase, previously reported by Lehvaslaiho et al. (EMBO J., 8, 159-166, 1989), EGF (10(-9)-10(-8) M) was found to induce marked increases of both [Ca2+]i and plasma membrane potential (investigated by the fura-2 and bis-oxonol techniques) which, in their initial phase, were only marginally dependent on the presence of Ca2+ in the incubation medium. These responses were inhibited, but only in part (40-50%) by phorbol ester activators of protein kinase C. Moreover, inositolphosphate analysis (by anion exchange chromatography) revealed hydrolysis of membrane polyphosphoinositides. All these effects of EGF were more prompt and much larger in NEN7 than NEN37 cells. The EGF concentration-dependence curves (measured by both [3H]thymidine incorporation and long-term proliferation assay) were quite different in the two cell clones. In the cells expressing the lower number of receptors measurable growth stimulation was observed at 10(-10), and maximal effect at 10(-9) M EGF. In NEN7 cells the curve was much more shallow, with measurable stimulation already at 10(-12) and maximal effect at 10(-8) M EGF. The maximal growth effect was approximately the same for the two cell clones. It is concluded that the intracellular signals identified here may play a limited role in the neu-induced cell proliferation, but are possibly involved in the acquisition of the tumoral phenotype typically expressed by the EGF-treated NEN7 cells.