P Bork

..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...

..We hypothesise that the identification of these genes should yield insights into the mechanisms by which prolactin participates in cancer formation or progression, and possibly how it regulates normal mammary gland development...

..The final goal will be to elucidate the mapping between genotype and phenotype...

..Phylogenetic and genomic location analysis of 20 complete eubacterial genomes suggests that this ancient duplication has been differentially lost and maintained in eubacteria...

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..A systematically derived motif database is therefore feasible, allowing the classification of the majority of the newly appearing protein sequences into known families...

..Phylogenetic analysis of all the proteins indicates a widespread sequence family for which a considerable number of isoenzymes can be inferred...

..While current homology detection methods can cope with the data flow, the identification, verification and annotation of functional features need to be drastically improved...

..Both human p15 homologues bind TAP, NXF2, and NXF3. Together, our results indicate that the TAP-p15 mRNA export pathway has diversified in higher eukaryotes compared to yeast, perhaps reflecting a greater substrate complexity...

..Users can access the complete set of orthologous groups via a web interface at: http://eggnog.embl.de...

..The results favour widespread recruitment of enzymes between pathways, rather than a "backwards evolution" model, and support the idea that modern proteins may have arisen from common ancestors that bound key metabolites...

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..The volume of the active site cleft accommodating the four residues omega - 1...omega + 2 appears to be approximately 540 A3...

..However, in the Werner and Bloom syndrome helicases the HRDC domain may have a role in their functional differences by mediating diverse molecular interactions...

..Our results further suggest that, although functions can be inferred for most proteins on earth, many functions remain to be discovered in numerous small, rare protein families...

..The flexible combination of active sites and three-dimensional folds observed in nature can be exploited by protein engineers in designing and optimizing enzymatic function...

..Furthermore, by utilising the new incoming data on single nucleotide polymorphisms by mapping them onto three-dimensional structures of proteins, problems concerning population, medical and evolutionary genetics can be addressed...

..The usefulness of STRING is illustrated with an example that suggests a functional context for an RNA methylase with unknown specificity...

..Using a combination of genomic context and homology searches, new functional features can be predicted for 10% of M. genitalium genes...

..SMART output can now be easily included in users' documents. A SMART mirror has been created at http://smart.ox.ac.uk...

..Other improvements include the ability to query SMART by Gene Ontology terms, improved structure database searching and batch retrieval of multiple entries...

..Various types of data such as genome sizes or protein domain repertoires can be mapped onto the tree. Export to several bitmap and vector graphics formats is supported. AVAILABILITY: iTOL is available at http://itol.embl.de..

..A comparison of coding exon sequences confirms the ancestral nature of Platynereis and human genes. Thus, the urbilaterian ancestor had complex, intron-rich genes that have been retained in Platynereis and human...

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..Our results illustrate that ARM and HEAT-repeat proteins, while having a common phylogenetic origin, have since diverged significantly. We discuss evolutionary scenarios that could account for the great diversity of repeats observed...

..Finally, we show that some genomes are more highly organized than others: they show a higher degree of the clustering of genes that have orthologs in other genomes...

..The method also enables determination of preferred habitats for entire microbial clades and provides evidence that such habitat preferences are often remarkably stable over time...

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..This type of information complements functional features that are predicted by classical homology-based search techniques...

..This structure may be very widely distributed throughout the biological world in sialidases and some other enzymes. In bacteria, a mobile noncatalytic domain is often associated with these same enzymes...

..Nevertheless, qualitatively interesting examples of conservation of gene order in eukaryotes can be observed...

..For example, we place the phylum Acidobacteria as a sister group of delta-Proteobacteria, support a Gram-positive origin of Bacteria, and suggest a thermophilic last universal common ancestor...

..In addition to the standard web access to the database, users can now query SMART using distributed annotation system (DAS) or through a simple object access protocol (SOAP) based web service...

..Users can query the resource for individual genes via a web interface or download the complete set of orthologous groups at http://eggnog.embl.de...

..A non-redundant collection of protein complexes from experimental data would be useful for biological interpretation, but manual assembly is tedious and often inconsistent...

..Novel features include AJAX-based web-navigation, inclusion of additional resources such as BioGRID, and detailed protein domain annotation. STRING is available at http://string.embl.de/..

..Furthermore, intrinsically disordered protein regions can be identified and displayed. The network context is now displayed in the results page for more than 350 000 proteins, enabling easy analyses of domain interactions...

..AVAILABILITY: The program is available upon request from the authors. A web server of BLAST2GENE is maintained at http://www.bork.embl.de/blast2gene..

..Several distinct, incomplete cycles reflect adaptations to different environments. Their distribution over the phylogenetic tree hints at precursors in the evolution of the citric-acid cycle...

..Archaean, bacterial and parasite specific adaptations are identified and described...

..To reveal unidentified regulatory signals, we combine information from experiments with computational approaches. Depending on available knowledge, three different strategies are employed...

..embl-heidelberg.de/beisenha/gpi/gpi_p rediction. html The algorithm has been implemented in the prototype software "big-Pi predictor" which may find application as a genome annotation and target selection tool...

..This person can extract from the text considerably more information than is immediately apparent due to his extended biological background knowledge and logical reasoning...

..We have experimentally verified that at least one of the newly formed proteins has a cellular localization different from RanBP2's, and we show that positive selection did act on specific domains during evolution...

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..XplorMed is available http://www.bork. embl-heidelberg.de/xplormed...

..The resource allows every association to be inspected visually and can be accessed at http://www.bork.embl.de/ArrayProspector...

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..Several questions arise as to whether the effort of scanning full text articles is worthy, or whether the information that can be extracted from the different sections of an article can be relevant...

..STRING currently holds 730,000 proteins in 180 fully sequenced organisms, and is available at http://string.embl.de/...

..Here we describe new features added to XplorMed during the last 2 years (http://www.bork.embl-heidelberg.de/xplormed/)...

..Representative expression profiles confirm that sequence diversification is accompanied by specific responses to different immune challenges. Alternative RNA splicing may also contribute to expansion of the immune repertoire...

..Version 8.0 of STRING covers about 2.5 million proteins from 630 organisms, providing the most comprehensive view on protein-protein interactions currently available. STRING can be reached at http://string-db.org/...

..The overall picture is of a huge diversity of gene content within eukaryotic genomes, reflecting different functional demands in different species...

..Gene loss, unlike the other processes, correlates fairly well with time. This clock-like behavior suggests that gene loss is under negative selection, while the processes that add genes are under positive selection...

..The CASH domain is characterized by internal repetitions of glycines and hydrophobic residues that correspond to the repetitive units of a predicted or observed right-handed beta-helix structure of the pectate lyase superfamily...

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..SHOT is a useful tool for analysing the tree of life from a genomic point of view. It is available at http://www.Bork.EMBL-Heidelberg.de/SHOT...

..Comparative genome analysis, thus, allows identification of a level of functional interaction between that of pairwise interactions, and of the complete genome...

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..Those relations are used to derive ensembles of related words and their associated subsets of abstracts. The algorithm can be used publicly at http:// www.bork.embl-heidelberg.de/xplormed/...

..To find potential targets for drugs active against pathogenic bacteria, we have searched all completely sequenced genomes of pathogenic bacteria for genes relevant for iron transport...

..The exploratory tool XplorMed has been developed to analyse the result of any MEDLINE query. It suggests main groups of related topics and documents, sparing the user the need of reading all abstracts...

..Here, we compare closely related genomes to identify the rate with which gene order is disrupted and to infer the genes involved in the genome rearrangement...

..A conserved tyrosine in the SAM sequences of the EPH related RPTKs is likely to mediate cell-cell initiated signal transduction via the binding of SH2 containing proteins to phosphotyrosine...

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..Availability: AQUA is implemented in Tcl/Tk and runs in command line on all platforms. The source code is available under the GNU GPL license. Source code, README and Supplementary data are available at http://www.bork.embl.de/Docu/AQUA...

..In this work, we choose the task of extracting information around this complex topic using a two-step procedure involving machine learning and information extraction...

..The database predicts functional interactions at an expected level of accuracy of at least 80% for more than half of the genes; it is online at http://www.bork.embl-heidelberg.de/STRING/...

..The data set provides a blueprint of the minimal cellular machinery required for life...

..Another distinct feature is that the user can specify a subregion of the input alignment in order to specifically analyze functional domains or exons of interest. The PAL2NAL server is available at http://www.bork.embl.de/pal2nal...

..The method thus enables the prediction of target processes and regulatory features for several hundred transcriptional regulators...

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..While the discoveries illustrate the opportunities in function discovery, we also discuss the immense conceptual and practical challenges that come along with this new type of data...

..The strongest selective pressure was detected for proteins involved in transcription regulation...

..Although many resistance genes (R genes) associated to HR have been identified, very little is known about the molecular mechanisms activated after their expression...

..4DXpress will be an invaluable tool for developmental as well as for computational biologists interested in gene regulation and evolution. 4DXpress is available at http://ani.embl.de/4DXpress...

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..The characterization of their domain composition and organization provides useful information on the specific role of each region of their sequence...

..This domain is characterized by a number of conserved aromatic and charged residues and is predicted to consist of three alpha helices. Recent studies indicate a likely DNA-binding function for the DDT domain...

..The average human genotype carries approximately 10(3) damaging non-synonymous SNPs that together cause a substantial reduction in fitness...

..Furthermore, the C-terminus of TAP was found to contain a ubiquitin-associated (UBA) domain. By site-directed mutagenesis we show that a conserved loop in this domain plays an essential role in mediating TAP-nucleoporin interaction...

..Notably, these structures also express different opsins, indicating that sea urchins possess an intricate molecular set-up to sense their environment...

..AVAILABILITY: The Sircah is available for download under a creative commons license along with additional documentation and a tutorial from http://www.bork.embl.de/Sircah...

..Lineage-specific functional repertoires of periodic-associated paralogues imply that this mode of regulation might have evolved independently in several organisms...

..Polyketides are a diverse group of biotechnologically important secondary metabolites that are produced by multi domain enzymes called polyketide synthases (PKS)...

..However, many evolutionary constraints can be uncovered only if temporal and spatial aspects are included in the network analysis...

..5 million genes across 373 genomes and their interactions contained in the STRING database. STITCH is available at http://stitch.embl.de/...

..The common nature of recent exon duplication indicates that it might have a significant role in the fast evolution of eukaryotic genes. It also provides a general mechanism for the regulation of protein function...

..We also consider interactions between complexes (cross-talk) and use these to construct a structure-based network of molecular machines in the cell...

..Human experts found the references that the algorithm scored highly were more relevant to the database entry than those scored lowly, suggesting that the algorithm was useful...

..However, we were able to assign pathways, cellular processes or physical complexes for 273 groups (encompassing 3624 previously functionally uncharacterized proteins)...

..The WWW server is at http://www.bork.embl-heidelberg.de/AnDom, and profiles can be downloaded at ftp.bork.embl-heidelberg.de/pub/users/ schmidt/AnDom...

..The approach outlined here identified a new set of genes frequently affected by mutations in MSI-positive tumor cells. It will lead to novel and highly specific diagnostic and therapeutic targets for microsatellite unstable cancers...

..A common evolutionary origin for all of the proteins in this class is proposed...

..The scoring also indicates that for some diseases, the chance of identifying the underlying gene is higher...

..The model suggests numerous experiments to probe exosome function, particularly with respect to subunits making direct atomic contacts and conserved, possibly functional residues within the predicted central pore of the complex...

..The genes and unprocessed pseudogenes obtained here will enable further studies on the mechanisms involved in gene duplication as well as of the fate of duplicated genes...