Genome sequences and great expectations

To assess how automatic function assignment will contribute to genome annotation in the next five years, we have performed an analysis of 31 available genome sequences. An emerging pattern is that function can be predicted for almost two-thirds of the 73,500 genes that were analyzed. Despite progress in computational biology, there will always be a great need for large-scale experimental determination of protein function

Brain Radiation Information Data Exchange (BRIDE): Integration of experimental data from low-dose ionising radiation research for pathway discovery

Background: The underlying molecular processes representing stress responses to low-dose ionising radiation (LDIR) in mammals are just beginning to be understood. In particular, LDIR effects on the brain and their possible association with neurodegenerative disease are currently being explored using omics technologies. Results: We describe a light-weight approach for the storage, analysis and distribution of relevant LDIR omics datasets. The data integration platform, called BRIDE, contains information from the literature as well as experimental information from transcriptomics and proteomics studies. It deploys a hybrid, distributed solution using both local storage and cloud technology. Conclusions: BRIDE can act as a knowledge broker for LDIR researchers, to facilitate molecular research on the systems biology of LDIR response in mammals. Its flexible design can capture a range of experimental information for genomics, epigenomics, transcriptomics, and proteomics. The data collection is available at:

Subgraphs in random networks

Understanding the subgraph distribution in random networks is important for modelling complex systems. In classic Erdos networks, which exhibit a Poissonian degree distribution, the number of appearances of a subgraph G with n nodes and g edges scales with network size as \mean{G} ~ N^{n-g}. However, many natural networks have a non-Poissonian degree distribution. Here we present approximate equations for the average number of subgraphs in an ensemble of random sparse directed networks, characterized by an arbitrary degree sequence. We find new scaling rules for the commonly occurring case of directed scale-free networks, in which the outgoing degree distribution scales as P(k) ~ k^{-\gamma}. Considering the power exponent of the degree distribution, \gamma, as a control parameter, we show that random networks exhibit transitions between three regimes. In each regime the subgraph number of appearances follows a different scaling law, \mean{G} ~ N^{\alpha}, where \alpha=n-g+s-1 for \gamma<2, \alpha=n-g+s+1-\gamma for 2<\gamma<\gamma_c, and \alpha=n-g for \gamma>\gamma_c, s is the maximal outdegree in the subgraph, and \gamma_c=s+1. We find that certain subgraphs appear much more frequently than in Erdos networks. These results are in very good agreement with numerical simulations. This has implications for detecting network motifs, subgraphs that occur in natural networks significantly more than in their randomized counterparts.Comment: 8 pages, 5 figure

The role of sequence conservation in the prediction of protein structure

SIGLEAvailable from British Library Document Supply Centre- DSC:DX182096 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Metabolic innovations towards the human lineage

Background: We describe a function-driven approach to the analysis of metabolism which takes into account the phylogenetic origin of biochemical reactions to reveal subtle lineage-specific metabolic innovations, undetectable by more traditional methods based on sequence comparison. The origins of reactions and thus entire pathways are inferred using a simple taxonomic classification scheme that describes the evolutionary course of events towards the lineage of interest. We investigate the evolutionary history of the human metabolic network extracted from a metabolic database, construct a network of interconnected pathways and classify this network according to the taxonomic categories representing eukaryotes, metazoa and vertebrates. Results: It is demonstrated that lineage-specific innovations correspond to reactions and pathways associated with key phenotypic changes during evolution, such as the emergence of cellular organelles in eukaryotes, cell adhesion cascades in metazoa and the biosynthesis of complex cell-specific biomolecules in vertebrates. Conclusion: This phylogenetic view of metabolic networks puts gene innovations within an evolutionary context, demonstrating how the emergence of a phenotype in a lineage provides a platform for the development of specialized traits