Fast assignment of protein structures to sequences using the intermediate sequence library PDB-ISL

MOTIVATION: For large-scale structural assignment to sequences, as in computational structural genomics, a fast yet sensitive sequence search procedure is essential. A new approach using intermediate sequences was tested as a shortcut to iterative multiple sequence search methods such as PSI-BLAST. RESULTS: A library containing potential intermediate sequences for proteins of known structure (PDB-ISL) was constructed. The sequences in the library were collected from a large sequence database using the sequences of the domains of proteins of known structure as the query sequences and the program PSI-BLAST. Sequences of proteins of unknown structure can be matched to distantly related proteins of known structure by using pairwise sequence comparison methods to find homologues in PDB-ISL. Searches of PDB-ISL were calibrated, and the number of correct matches found at a given error rate was the same as that found by PSI-BLAST. The advantage of this library is that it uses pairwise sequence comparison methods, such as FASTA or BLAST2, and can, therefore, be searched easily and, in many cases, much more quickly than an iterative multiple sequence comparison method. The procedure is roughly 20 times faster than PSI-BLAST for small genomes and several hundred times for large genomes. AVAILABILITY: Sequences can be submitted to the PDB-ISL servers at http://stash.mrc-lmb.cam.ac.uk/PDB_ISL/ or http://cyrah.ebi.ac.uk:1111/Serv/PDB_ISL/ and can be downloaded from ftp://ftp.ebi.ac.uk/pub/contrib/jong/PDB_+ ++ISL/ CONTACT: sat@mrc-lmb.cam.ac.uk and jong@ebi.ac.uk     

TOPAL 2.0: improved detection of mosaic sequences within multiple alignments

MOTIVATION: The Dss statistic was proposed by McGuire et al. (Mol. Biol. Evol., 14, 1125-1131, 1997) for scanning data sets for the presence of recombination, an important step in some phylogenetic analyses. The statistic, however, could not distinguish well between among-site rate variation and recombination, and had no statistical test for significant values. This paper addresses these shortfalls. RESULTS: A modification to the Dss statistic is proposed which accounts for rate variation to a large extent. A statistical test, based on parametric bootstrapping, is also suggested. AVAILABILITY: The TOPAL package (version 2) may be accessed from http:/ /www.bioss.sari.ac.uk/frank/Genetics and by anonymous ftp from typ://ftp.bioss.sari.ac.uk in the directory pub/phylogeny/topal. CONTACT: frank@bioss.sari.ac.uk     

GOLD--graphical overview of linkage disequilibrium

SUMMARY: We describe a software package that provides a graphical summary of linkage disequilibrium in human genetic data. It allows for the analysis of family data and is well suited to the analysis of dense genetic maps. AVAILABILITY: http://www.well.ox.ac.uk/asthma/GOLD CONTACT: goncalo@well.ox.ac.uk     

Swissknife - 'lazy parsing' of SWISS-PROT entries.

SUMMARY: We present Swissknife, a set of Perl modules which provides a fast and reliable object-oriented interface to parsing and modifying files in SWISS-PROT format. AVAILABILITY: The Swissknife modules are available at ftp://ftp.ebi.ac. uk/pub/software/swissprot/. CONTACT: hhe@ebi.ac.uk     

VARSPLIC: alternatively-spliced protein sequences derived from SWISS-PROT and TrEMBL

SUMMARY: The program varsplic.pl uses information present in the SWISS-PROT and TrEMBL databases to create new records for alternatively spliced isoforms. These new records can be used in similarity searches. AVAILABILITY: The program is available at ftp://ftp.ebi.ac.uk/pub/software/swissprot/, together with regularly updated output files. CONTACT: pkersey@ebi.ac.uk     

Circles: automating the comparative analysis of RNA secondary structure

SUMMARY: Circles is a program for inferring RNA secondary structure using maximum weight matching. The program can read in an alignment in FASTA, ClustalW, or NEXUS format, compute a maximum weight matching, and export one or more secondary structures in various file formats. AVAILABILITY: The program is available at no cost from http://taxonomy.zoology.gla.ac.uk/rod/circles/ and requires Windows 95/98/NT. CONTACT: r.page@bio.gla.ac.uk     

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/     

Sequence type analysis and recombinational tests (START).

The 32-bit Windows application START is implemented using Visual Basic and C(++) and performs analyses to aid in the investigation of bacterial population structure using multilocus sequence data. These analyses include data summary, lineage assignment, and tests for recombination and selection. AVAILABILITY: START is available at http://outbreak.ceid.ox.ac.uk/software.htm. CONTACT: keith.jolley@ceid.ox.ac.uk     

XEMBL: distributing EMBL data in XML format

Data in the EMBL Nucleotide Sequence Database is traditionally available in a flat file format that has a number of known shortcomings. With XML rapidly emerging as a standard data exchange format that can address some problems of flat file formats by defining data structure and syntax, there is now a demand to distribute EMBL data in an XML format. XEMBL is a service tool that employs CORBA servers to access EMBL data, and distributes the data in XML format via a number of mechanisms. AVAILABILITY: Use of the XEMBL service is free of charge at http://www.ebi.ac.uk/xembl/, and can be accessed via web forms, CGI, and a SOAP-enabled service. SUPPLEMENTARY INFORMATION: Information on the EMBL Nucleotide Sequence Database is available at http://www.ebi.ac.uk/embl/. The EMBL Object Model is available at http://corba.ebi.ac.uk/models/. Information on the EMBL CORBA servers is at http://corba.ebi.ac.uk/     

LVB: parsimony and simulated annealing in the search for phylogenetic trees

The program LVB seeks parsimonious phylogenies from nucleotide alignments, using the simulated annealing heuristic. LVB runs fast and gives high quality results. AVAILABILITY: The software is available at http://www.rubic.reading.ac.uk/lvb/ Supplementary information: Supplementary information may be downloaded from http://www.rubic.reading.ac.uk/~daniel/     

A proposal for a standard CORBA interface for genome maps

MOTIVATION: The scientific community urgently needs to standardize the exchange of biological data. This is helped by the use of a common protocol and the definition of shared data structures. We have based our standardization work on CORBA, a technology that has become a standard in the past years and allows interoperability between distributed objects. RESULTS: We have defined an IDL specification for genome maps and present it to the scientific community. We have implemented CORBA servers based on this IDL to distribute RHdb and HuGeMap maps. The IDL will co-evolve with the needs of the mapping community. AVAILABILITY: The standard IDL for genome maps is available at http:// corba.ebi.ac.uk/RHdb/EUCORBA/MapIDL.htm l. The IORs to browse maps from Infobiogen and EBI are at http://www.infobiogen.fr/services/Hugemap/IOR and http://corba.ebi.ac.uk/RHdb/EUCORBA/IOR CONTACT: manu@infobiogen.fr, tome@ebi.ac.uk     

TAMBIS: transparent access to multiple bioinformatics information sources

SUMMARY: TAMBIS (Transparent Access to Multiple Bioinformatics Information Sources) is an application that allows biologists to ask rich and complex questions over a range of bioinformatics resources. It is based on a model of the knowledge of the concepts and their relationships in molecular biology and bioinformatics. AVAILABILITY: TAMBIS is available as an applet from http://img.cs.man.ac.uk/tambis SUPPLEMENTARY: A full manual, tutorial and videos can be found at http://img.cs.man.ac.uk/tambis. CONTACT: tambis@cs.man.ac.uk     

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     

Parallelized multiple alignment

SUMMARY: Multiple sequence alignment is a frequently used technique for analyzing sequence relationships. Compilation of large alignments is computationally expensive, but processing time can be considerably reduced when the computational load is distributed over many processors. Parallel processing functionality in the form of single-instruction multiple-data (SIMD) technology was implemented into the multiple alignment program Praline by using 'message passing interface' (MPI) routines. Over the alignments tested here, the parallelized program performed up to ten times faster on 25 processors compared to the single processor version. AVAILABILITY: Example program code for parallelizing pairwise alignment loops is available from http://mathbio.nimr.mrc.ac.uk/~jkleinj/tools/mpicode. The 'message passing interface' package (MPICH) is available from http:/www.unix.mcs.anl.gov/mpi/mpich. CONTACT: jhering@nimr.mrc.ac.uk SUPPLEMENTARY INFORMATION: Praline is accessible at http://mathbio.nimr.mrc.ac.uk/praline.     

famCNV: copy number variant association for quantitative traits in families

A program package to enable genome-wide association of copy number variants (CNVs) with quantitative phenotypes in families of arbitrary size and complexity. Intensity signals that act as proxies for the number of copies are modeled in a variance component framework and association with traits is assessed through formal likelihood testing. AVAILABILITY AND IMPLEMENTATION: The Java package is made available at www.imperial.ac.uk/medicine/people/m.falchi/. CONTACT: m.falchi@imperial.ac.uk.     

CHROMA: consensus-based colouring of multiple alignments for publication

CHROMA annotates multiple protein sequence alignments by consensus to produce formatted and coloured text suitable for incorporation into other documents for publication. The package is designed to be flexible and reliable, and has a simple-to-use graphical user interface running under Microsoft Windows. Both the executables and source code for CHROMA running under Windows and Linux (portable command-line only) are freely available at http://www.lg.ndirect.co.uk/chroma. Software enquiries should be directed to CHROMA@lg.ndirect.co.uk.     

Sequence search algorithm assessment and testing toolkit (SAT)

MOTIVATION: The Sequence Search Algorithm Assessment and Testing Toolkit (SAT) aims to be a complete package for the comparison of different protein homology search algorithms. The structural classification of proteins can provide us with a clear criterion for judgment in homology detection. There have been several assessments based on structural sequences with classifications but a good deal of similar work is now being repeated with locally developed procedures and programs. The SAT will provide developers with a complete package which will save time and produce more comparable performance assessments for search algorithms. The package is complete in the sense that it provides a non-redundant large sequence resource database, a well-characterized query database of proteins domains, all the parsers and some previous results from PSI-BLAST and a hidden markov model algorithm. RESULTS: An analysis on two different data sets was carried out using the SAT package. It compared the performance of a full protein sequence database (RSDB100) with a non-redundant representative sequence database derived from it (RSDB50). The performance measurement indicated that the full database is sub-optimal for a homology search. This result justifies the use of much smaller and faster RSDB50 than RSDB100 for the SAT. AVAILABILITY: A web site is up. The whole packa ge is accessible via www and ftp. ftp://ftp.ebi.ac.uk/pub/contrib/jong/SAT http://cyrah.ebi.ac.uk:1111/Proj/Bio/SAT http://www.mrc-lmb.cam.ac.uk/genomes/SAT In the package, some previous assessment results produced by the package can also be found for reference. CONTACT: jong@ebi.ac.uk     

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).     

Clustal W and Clustal X version 2.0

SUMMARY: The Clustal W and Clustal X multiple sequence alignment programs have been completely rewritten in C++. This will facilitate the further development of the alignment algorithms in the future and has allowed proper porting of the programs to the latest versions of Linux, Macintosh and Windows operating systems. AVAILABILITY: The programs can be run on-line from the EBI web server: http://www.ebi.ac.uk/tools/clustalw2. The source code and executables for Windows, Linux and Macintosh computers are available from the EBI ftp site ftp://ftp.ebi.ac.uk/pub/software/clustalw2/