A new family of carbon-nitrogen hydrolases.

Using computer methods for database search and multiple alignment, statistically significant sequence similarities were identified between several nitrilases with distinct substrate specificity, cyanide hydratases, aliphatic amidases, beta-alanine synthase, and a few other proteins with unknown molecular function. All these proteins appear to be involved in the reduction of organic nitrogen compounds and ammonia production. Sequence conservation over the entire length, as well as the similarity in the reactions catalyzed by the known enzymes in this family, points to a common catalytic mechanism. The new family of enzymes is characterized by several conserved motifs, one of which contains an invariant cysteine that is part of the catalytic site in nitrilases. Another highly conserved motif includes an invariant glutamic acid that might also be involved in catalysis.     

Systematic association of genes to phenotypes by genome and literature mining

One of the major challenges of functional genomics is to unravel the connection between genotype and phenotype. So far no global analysis has attempted to explore those connections in the light of the large phenotypic variability seen in nature. Here, we use an unsupervised, systematic approach for associating genes and phenotypic characteristics that combines literature mining with comparative genome analysis. We first mine the MEDLINE literature database for terms that reflect phenotypic similarities of species. Subsequently we predict the likely genomic determinants: genes specifically present in the respective genomes. In a global analysis involving 92 prokaryotic genomes we retrieve 323 clusters containing a total of 2,700 significant gene–phenotype associations. Some clusters contain mostly known relationships, such as genes involved in motility or plant degradation, often with additional hypothetical proteins associated with those phenotypes. Other clusters comprise unexpected associations; for example, a group of terms related to food and spoilage is linked to genes predicted to be involved in bacterial food poisoning. Among the clusters, we observe an enrichment of pathogenicity-related associations, suggesting that the approach reveals many novel genes likely to play a role in infectious diseases.     

Functional clues for hypothetical proteins based on genomic context analysis in prokaryotes

Three integrated genomic context methods were used to annotate uncharacterized proteins in 102 bacterial genomes. Of 7853 orthologous groups with unknown function containing 45110 proteins, 1738 groups could be linked to functionally associated partners. In many cases, those partners are uncharacterized themselves (hinting at newly identified modules) or have been described in general terms only. However, we were able to assign pathways, cellular processes or physical complexes for 273 groups (encompassing 3624 previously functionally uncharacterized proteins).     

HGBASE: a database of SNPs and other variations in and around human genes

Human genome polymorphism is expected to play a key role in defining the etiologic basis of phenotypic differences between individuals in aspects such as drug responses and common disease predisposition. Relevant functional DNA changes will probably be located in or near to transcribed sequences, and include many single nucleotide polymorphisms. To aid the future analysis of such genome variation, HGBASE (Human Genic Bi-Allelic SEquences) was constructed as a means to gather human gene-linked polymorphisms from all possible public sources, and show these as a non-redundant set of records in a standardized and user-friendly database endowed with text and sequence based search facilities. After 1 year of presence on the WWW, the HGBASE project has compiled data for over 22 000 records, and this number continues to triple every 6-12 months with data harvested or submitted from all major public genome databases and published literature from the previous decade. Extensive annotation enhancement, internal consistency checking and manual review of every record is undertaken to address potential errors and deficiencies sometimes present in the original source data. The fully polished and comprehensive database is made freely available to all at http://hgbase.cgr.ki.se     

NAIL-Network Analysis Interface for Linking HMMER results

SUMMARY: Network Analysis Interface for Linking HMMER results (NAIL) is a web-based tool for the analysis of results from a HMMER protein database-search. NAIL facilitates the selection of protein hits and the creation of an alignment, which can be used for a new sequence similarity search.     

Consistency of genome-based methods in measuring Metazoan evolution

Seven distinct genome-wide divergence measures were applied pairwise to the nine sequenced animal genomes of human, mouse, rat, chicken, pufferfish, fruit fly, mosquito, and two nematode worms (Caenorhabditis briggsae and Caenorhabditis elegans). Qualitatively, all of these divergence measures are found to correlate with the estimated time since speciation; however, marked deviations are observed in a few lineages. The distinct genome divergence measures also correlate well among themselves, indicating that most of the processes shaping genomes are dominated by neutral events. The deviations from the clock-like scenario in some lineages are observed consistently by several measures, implicitly confirming their reliability.