ProServer: a simple, extensible Perl DAS server

SUMMARY: The increasing size and complexity of biological databases has led to a growing trend to federate rather than duplicate them. In order to share data between federated databases, protocols for the exchange mechanism must be developed. One such data exchange protocol that is widely used is the Distributed Annotation System (DAS). For example, DAS has enabled small experimental groups to integrate their data into the Ensembl genome browser. We have developed ProServer, a simple, lightweight, Perl-based DAS server that does not depend on a separate HTTP server. The ProServer package is easily extensible, allowing data to be served from almost any underlying data model. Recent additions to the DAS protocol have enabled both structure and alignment (sequence and structural) data to be exchanged. ProServer allows both of these data types to be served. AVAILABILITY: ProServer can be downloaded from http://www.sanger.ac.uk/proserver/ or CPAN http://search.cpan.org/~rpettett/. Details on the system requirements and installation of ProServer can be found at http://www.sanger.ac.uk/proserver/.     

ProPred1: prediction of promiscuous MHC Class-I binding sites

SUMMARY: ProPred1 is an on-line web tool for the prediction of peptide binding to MHC class-I alleles. This is a matrix-based method that allows the prediction of MHC binding sites in an antigenic sequence for 47 MHC class-I alleles. The server represents MHC binding regions within an antigenic sequence in user-friendly formats. These formats assist user in the identification of promiscuous MHC binders in an antigen sequence that can bind to large number of alleles. ProPred1 also allows the prediction of the standard proteasome and immunoproteasome cleavage sites in an antigenic sequence. This server allows identification of MHC binders, who have the cleavage site at the C terminus. The simultaneous prediction of MHC binders and proteasome cleavage sites in an antigenic sequence leads to the identification of potential T-cell epitopes. AVAILABILITY: Server is available at http://www.imtech.res.in/raghava/propred1/. Mirror site of this server is available at http://bioinformatics.uams.edu/mirror/propred1/ Supplementary information: Matrices and document on server are available at http://www.imtech.res.in/raghava/propred1/page2.html     

Selecton: a server for detecting evolutionary forces at a single amino-acid site

SUMMARY: We present an algorithmic tool for the identification of biologically significant amino acids in proteins of known three dimensional structure. We estimate the degree of purifying selection and positive Darwinian selection at each site and project these estimates onto the molecular surface of the protein. Thus, patches of functional residues (undergoing either positive or purifying selection), which may be discontinuous in the linear sequence, are revealed. We test for the statistical significance of the site-specific scores in order to obtain reliable and valid estimates. AVAILABILITY: The Selecton web server is available at: http://selecton.bioinfo.tau.ac.il SUPPLEMENTARY INFORMATION: More information is available at http://selecton.bioinfo.tau.ac.il/overview.html. A set of examples is available at http://selecton.bioinfo.tau.ac.il/gallery.html.     

HuGeMap: a distributed and integrated Human Genome Map database.

The HuGeMap database stores the major genetic and physical maps of the human genome. It is also interconnected with the gene radiation hybrid mapping database RHdb. HuGeMap is accessible through a Web server for interactive browsing at URL http://www.infobiogen. fr/services/Hugemap , as well as through a CORBA server for effective programming. HuGeMap is intended as an attempt to build open, interconnected databases, that is databases that distribute their objects worldwide in compliance with a recognized standard of distribution. Maps can be displayed and compared with a java applet (http://babbage.infobiogen.fr:15000/Mappet/Show. html ) that queries the HuGeMap ORB server as well as the RHdb ORB server at the EBI.     

CRH_Server: an online comparative and radiation hybrid mapping server for the canine genome

SUMMARY: CRH_Server is an on line Comparative and Radiation Hybrid mapping Server dedicated to canine genomics. CRH_Server allows users to compute their own RH data using the current canine RH map, and allows comparative dog/human mapping analyses. Finally, it suggests multiple options for storage and queries of the dog RH database. AVAILABILITY: http://idefix.univ-rennes1.fr:8080/Dogs/rh-server.html. SUPPLEMENTARY INFORMATION: All information is available at http://idefix.univ-rennes1.fr:8080/Dogs/help_rh-server.html.     

meta-PPISP: a meta web server for protein-protein interaction site prediction

A number of complementary methods have been developed for predicting protein-protein interaction sites. We sought to increase prediction robustness and accuracy by combining results from different predictors, and report here a meta web server, meta-PPISP, that is built on three individual web servers: cons-PPISP (http://pipe.scs.fsu.edu/ppisp.html), Promate (http://bioportal.weizmann.ac.il/promate), and PINUP (http://sparks.informatics.iupui.edu/PINUP/). A linear regression method, using the raw scores of the three servers as input, was trained on a set of 35 nonhomologous proteins. Cross validation showed that meta-PPISP outperforms all the three individual servers. At coverages identical to those of the individual methods, the accuracy of meta-PPISP is higher by 4.8 to 18.2 percentage points. Similar improvements in accuracy are also seen on CAPRI and other targets. AVAILABILITY: meta-PPISP can be accessed at http://pipe.scs.fsu.edu/meta-ppisp.html     

Genomes OnLine Database (GOLD 1.0): a monitor of complete and ongoing genome projects world-wide.

SUMMARY: GOLD (Genomes On Line Database) is a World Wide Web resource for comprehensive access to information regarding complete and ongoing genome projects around the world. AVAILABILITY: GOLD is based at the University of Illinois at Urbana-Champaign and is available at http://geta.life.uiuc.edu/ approximately nikos/genomes. html. It is also mirrored at the European Bioinformatics Institute at http://www.ebi.ac.uk/research/cgg/genomes.html. CONTACT: genomes@ebi.ac.uk     

RadCon: phylogenetic tree comparison and consensus

SUMMARY: RadCon is a Macintosh program for manipulating and analysing phylogenetic trees. The program can determine the Cladistic Information Content of individual trees, the stability of leaves across a set of bootstrap trees, produce the strict basic Reduced Cladistic Consensus profile of a set of trees and convert a set of trees into its matrix representation for supertree construction. AVAILABILITY: The program is free and available at http://taxonomy.zoology.gla.ac.uk/ approximately jthorley/radcon/radcon.html.     

ConSurf: identification of functional regions in proteins by surface-mapping of phylogenetic information

SUMMARY: We recently developed algorithmic tools for the identification of functionally important regions in proteins of known three dimensional structure by estimating the degree of conservation of the amino-acid sites among their close sequence homologues. Projecting the conservation grades onto the molecular surface of these proteins reveals patches of highly conserved (or occasionally highly variable) residues that are often of important biological function. We present a new web server, ConSurf, which automates these algorithmic tools. ConSurf may be used for high-throughput characterization of functional regions in proteins. AVAILABILITY: The ConSurf web server is available at:http://consurf.tau.ac.il. SUPPLEMENTARY INFORMATION: A set of examples is available at http://consurf.tau.ac.il under 'GALLERY'.     

InterProScan--an integration platform for the signature-recognition methods in InterPro

InterProScan is a tool that scans given protein sequences against the protein signatures of the InterPro member databases, currently--PROSITE, PRINTS, Pfam, ProDom and SMART. The number of signature databases and their associated scanning tools as well as the further refinement procedures make the problem complex. InterProScan is designed to be a scalable and extensible system with a robust internal architecture. AVAILABILITY: The Perl-based InterProScan implementation is available from the EBI ftp server (ftp://ftp.ebi.ac.uk/pub/software/unix/iprscan/) and the SRS-basedInterProScan is available upon request. We provide the public web interface (http://www.ebi.ac.uk/interpro/scan.html) as well as email submission server (interproscan@ebi.ac.uk).     

ADAPTSITE: detecting natural selection at single amino acid sites.

ADAPTSITE is a program package for detecting natural selection at single amino acid sites, using a multiple alignment of protein-coding sequences for a given phylogenetic tree. The program infers ancestral codons at all interior nodes, and computes the total numbers of synonymous (c(S)) and nonsynonymous (c(N)) substitutions as well as the average numbers of synonymous (s(S)) and nonsynonymous (s(N)) sites for each codon site. The probabilities of occurrence of synonymous and nonsynonymous substitutions are approximated by s(S) / (s(S) + s(N)) and s(N) / (s(S) + s(N)), respectively. The null hypothesis of selective neutrality is tested for each codon site, assuming a binomial distribution for the probability of obtaining c(S) and c(N). AVAILABILITY: ADAPTSITE is available free of charge at the World-Wide Web sites http://mep.bio.psu.edu/adaptivevol.html and http://www.cib.nig.ac.jp/dda/yossuzuk/welcome.html. The package includes the source code written in C, binary files for UNIX operating systems, manual, and example files.     

The RDP-II (Ribosomal Database Project)

The Ribosomal Database Project (RDP-II), previously described by Maidak et al. [Nucleic Acids Res. (2000), 28, 173-174], continued during the past year to add new rRNA sequences to the aligned data and to improve the analysis commands. Release 8.0 (June 1, 2000) consisted of 16 277 aligned prokaryotic small subunit (SSU) rRNA sequences while the number of eukaryotic and mitochondrial SSU rRNA sequences in aligned form remained at 2055 and 1503, respectively. The number of prokaryotic SSU rRNA sequences more than doubled from the previous release 14 months earlier, and approximately 75% are longer than 899 bp. An RDP-II mirror site in Japan is now available (http://wdcm.nig.ac.jp/RDP/html/index.h tml). RDP-II provides aligned and annotated rRNA sequences, derived phylogenetic trees and taxonomic hierarchies, and analysis services through its WWW server (http://rdp.cme.msu.edu/). Analysis services include rRNA probe checking, approximate phylogenetic placement of user sequences, screening user sequences for possible chimeric rRNA sequences, automated alignment, production of similarity matrices and services to plan and analyze terminal restriction fragment polymorphism experiments. The RDP-II email address for questions and comments has been changed from curator@cme.msu.edu to rdpstaff@msu.edu.     

EMBL-Align: a new public nucleotide and amino acid multiple sequence alignment database

The submission of multiple sequence alignment data to EMBL has grown 30-fold in the past 10 years, creating a problem of archiving them. The EBI has developed a new public database of multiple sequence alignments called EMBL-Align. It has a dedicated web-based submission tool, Webin-Align. Together they represent a comprehensive data management solution for alignment data. Webin-Align accepts all the common alignment formats and can display data in CLUSTALW format as well as a new standard EMBL-Align flat file format. The alignments are stored in the EMBL-Align database and can be queried from the EBI SRS (Sequence Retrieval System) server. AVAILABILITY: Webin-Align: http://www.ebi.ac.uk/embl/Submission/align_top.html, EMBL-Align: ftp://ftp.ebi.ac.uk/pub/databases/embl/align, http://srs.ebi.ac.uk/     

GTOP: a database of protein structures predicted from genome sequences

Large-scale genome projects generate an unprecedented number of protein sequences, most of them are experimentally uncharacterized. Predicting the 3D structures of sequences provides important clues as to their functions. We constructed the Genomes TO Protein structures and functions (GTOP) database, containing protein fold predictions of a huge number of sequences. Predictions are mainly carried out with the homology search program PSI-BLAST, currently the most popular among high-sensitivity profile search methods. GTOP also includes the results of other analyses, e.g. homology and motif search, detection of transmembrane helices and repetitive sequences. We have completed analyzing the sequences of 41 organisms, with the number of proteins exceeding 120 000 in total. GTOP uses a graphical viewer to present the analytical results of each ORF in one page in a ‘color-bar’ format. The assigned 3D structures are presented by Chime plug-in or RasMol. The binding sites of ligands are also included, providing functional information. The GTOP server is available at http://spock.genes.nig.ac.jp/~genome/gtop.html.     

ProPred: prediction of HLA-DR binding sites.

ProPred is a graphical web tool for predicting MHC class II binding regions in antigenic protein sequences. The server implement matrix based prediction algorithm, employing amino-acid/position coefficient table deduced from literature. The predicted binders can be visualized either as peaks in graphical interface or as colored residues in HTML interface. This server might be a useful tool in locating the promiscuous binding regions that can bind to several HLA-DR alleles. AVAILABILITY: The server is available at http://www.imtech.res.in/raghava/propred/ CONTACT: raghava@imtech.res.in SUPPLEMENTARY INFORMATION: http://www.imtech.res.in/raghava/propred/page3.html     

Dasty3, a WEB framework for DAS

MOTIVATION: Dasty3 is a highly interactive and extensible Web-based framework. It provides a rich Application Programming Interface upon which it is possible to develop specialized clients capable of retrieving information from DAS sources as well as from data providers not using the DAS protocol. Dasty3 provides significant improvements on previous Web-based frameworks and is implemented using the 1.6 DAS specification. AVAILABILITY: Dasty3 is an open-source tool freely available at http://www.ebi.ac.uk/dasty/ under the terms of the GNU General public license. Source and documentation can be found at http://code.google.com/p/dasty/. CONTACT: hhe@ebi.ac.uk.     

Soap-HT-BLAST: high throughput BLAST based on Web services

SUMMARY: A high throughput Basic Local Alignment Search Tool (BLAST) system based on Web services is implemented. It provides an alternative BLAST service and allows users to perform multiple BLAST queries at one run in a distributed, parallel environment through the Internet. AVAILABILITY: It is available at http://mammoth.bii.a-star.edu.sg/webservices/htblast/index.html and at http://www.bii.a-star.edu.sg/jiren/download.html     

TM Finder: a prediction program for transmembrane protein segments using a combination of hydrophobicity and nonpolar phase helicity scales

Based on the principle of dual prediction by segment hydrophobicity and nonpolar phase helicity, in concert with imposed threshold values of these two parameters, we developed the automated prediction program TM Finder that can successfully locate most transmembrane (TM) segments in proteins. The program uses the results of experiments on a series of host-guest TM segment mimic peptides of prototypic sequence KK AAAXAAAAAXAAWAAXAAAKKKK-amide (where X = each of the 20 commonly occurring amino acids) through which an HPLC-derived hydropathy scale, a hydrophobicity threshold for spontaneous membrane insertion, and a nonpolar phase helical propensity scale were determined. Using these scales, the optimized prediction algorithm of TM Finder defines TM segments by first searching for competent core segments using the combination of hydrophobicity and helicity scales, and then performs a gap-joining operation, which minimizes prediction bias caused by local hydrophilic residues and/or the choice of window size. In addition, the hydrophobicity threshold requirement enables TM Finder to distinguish reliably between membrane proteins and globular proteins, thereby adding an important dimension to the program. A full web version of the TM Finder program can be accessed at http://www.bioinformatics-canada.org/TM/.     

Taxonomy workbench.

At advanced stages of working with user-defined protein and gene sequence collections, it is frequently necessary to link these data to the taxonomic tree and to extract subsets in accordance with taxonomic considerations. Since no general automatic tools had been available, this was a tedious manual effort. Our taxonomy workbench allows processing of sequence sets, mapping of these sets onto the taxonomic tree, collection of taxonomic subsets from them and printing of the whole tree or some part of it. As a side effect, the system enables queries to and navigation within the taxonomy database. AVAILABILITY: An implementation of the taxonomy workbench is accessible for public use as a www-service at http://mendel.imp.univie.ac.at/taxonomy/. Software components for the command-line and for the www-version are available on request. CONTACT: Georg.Schneider@nt.imp.univie.ac.at; Frank.Eisenhaber@nt.imp.univie.ac.at SUPPLEMENTARY INFORMATION: Documentation for the taxonomy workbench can be accessed at http://mendel.imp.univie.ac.at/taxonomy/help.html.