Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.

/pdf/gene-ontology-tool-for-the-unification-of-biology-ppsktrcye3.pdf

Gene Ontology: tool for the unification of biology

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/

Contact: clustalw@ucd.ie

Clustal W and Clustal X version 2.0

Pfam is a widely used database of protein families and domains. This article describes a set of major updates that we have implemented in the latest release (version 24.0). The most important change is that we now use HMMER3, the latest version of the popular profile hidden Markov model package. This software is approximately 100 times faster than HMMER2 and is more sensitive due to the routine use of the forward algorithm. The move to HMMER3 has necessitated numerous changes to Pfam that are described in detail. Pfam release 24.0 contains 11,912 families, of which a large number have been significantly updated during the past two years. Pfam is available via servers in the UK (http://pfam.sanger.ac.uk/), the USA (http://pfam.janelia.org/) and Sweden (http://pfam.sbc.su.se/).

/pdf/the-pfam-protein-families-database-3t3lguk949.pdf

The Pfam protein families database

The use of some multiple-sequence alignments in phylogenetic analysis, particularly those that are not very well conserved, requires the elimination of poorly aligned positions and divergent regions, since they may not be homologous or may have been saturated by multiple substitutions. A computerized method that eliminates such positions and at the same time tries to minimize the loss of informative sites is presented here. The method is based on the selection of blocks of positions that fulfill a simple set of requirements with respect to the number of contiguous conserved positions, lack of gaps, and high conservation of flanking positions, making the final alignment more suitable for phylogenetic analysis. To illustrate the efficiency of this method, alignments of 10 mitochondrial proteins from several completely sequenced mitochondrial genomes belonging to diverse eukaryotes were used as examples. The percentages of removed positions were higher in the most divergent alignments. After removing divergent segments, the amino acid composition of the different sequences was more uniform, and pairwise distances became much smaller. Phylogenetic trees show that topologies can be different after removing conserved blocks, particularly when there are several poorly resolved nodes. Strong support was found for the grouping of animals and fungi but not for the position of more basal eukaryotes. The use of a computerized method such as the one presented here reduces to a certain extent the necessity of manually editing multiple alignments, makes the automation of phylogenetic analysis of large data sets feasible, and facilitates the reproduction of the final alignment by other researchers.

/pdf/selection-of-conserved-blocks-from-multiple-alignments-for-i0qfazjwh5.pdf

Selection of Conserved Blocks from Multiple Alignments for Their Use in Phylogenetic Analysis

Summary: Jalview Version 2 is a system for interactive WYSIWYG editing, analysis and annotation of multiple sequence alignments. Core features include keyboard and mouse-based editing, multiple views and alignment overviews, and linked structure display with Jmol. Jalview 2 is available in two forms: a lightweight Java applet for use in web applications, and a powerful desktop application that employs web services for sequence alignment, secondary structure prediction and the retrieval of alignments, sequences, annotation and structures from public databases and any DAS 1.53 compliant sequence or annotation server.

Availability: The Jalview 2 Desktop application and JalviewLite applet are made freely available under the GPL, and can be downloaded from www.jalview.org

Contact: g.j.barton@dundee.ac.uk

/pdf/jalview-version-2-a-multiple-sequence-alignment-editor-and-3pguchayjh.pdf

Jalview Version 2--a multiple sequence alignment editor and analysis workbench.

The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl.html) constitutes Europe's primary nucleotide sequence resource. Main sources for DNA and RNA sequences are direct submissions from individual researchers, genome sequencing projects and patent applications. While automatic procedures allow incorporation of sequence data from large-scale genome sequencing centres and from the European Patent Office (EPO), the preferred submission tool for individual submitters is Webin (WWW). Through all stages, dataflow is monitored by EBI biologists communicating with the sequencing groups. In collaboration with DDBJ and GenBank the database is produced, maintained and distributed at the European Bioinformatics Institute (EBI). Database releases are produced quarterly and are distributed on CD-ROM. Network services allow access to the most up-to-date data collection via Internet and World Wide Web interface. EBI's Sequence Retrieval System (SRS) is a Network Browser for Databanks in Molecular Biology, integrating and linking the main nucleotide and protein databases, plus many specialised databases. For sequence similarity searching a variety of tools (e.g. Blitz, Fasta, Blast etc) are available for external users to compare their own sequences against the most currently available data in the EMBL Nucleotide Sequence Database and SWISS-PROT.

/pdf/the-embl-nucleotide-sequence-database-4jalicikpk.pdf

The EMBL Nucleotide Sequence Database

The IMGT/HLA database (http://www.ebi.ac.uk/imgt/hla) has provided a centralized repository for the sequences of the alleles named by the WHO Nomenclature Committee for Factors of the HLA System for the past four years. Since its initial release the database has grown and is the primary source of information for the study of sequences of the human major histocompatibilty complex. The initial release of the database contained a limited number of tools. As a result of feedback from our users and developments in HLA we have been able to provide new tools and facilities. The HLA sequences have also been extended to include intron sequences and the 3' and 5' untranslated regions in the alignments and also the inclusion of new genes such as MICA. The IMGT/MHC database (http://www.ebi.ac.uk/imgt/mhc) was released in March 2002 to provide a similar resource for other species. The first release of IMGT/MHC contains the sequences of non-human primates (apes, new and old world monkeys), canines and feline sequences. Further species will be added shortly and the database aims to become the primary source of MHC data for non-human sequences.

IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex

The Immuno Polymorphism Database (IPD), http://www.ebi.ac.uk/ipd/ is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer-cell immunoglobulin-like receptors, IPD-MHC, a database of sequences of the major histocompatibility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The data is currently available online from the website and FTP directory. This article describes the latest updates and additional tools added to the IPD project.

IPD - The Immuno-Polymorphism Database

Summary: To allow efficient and systematic retrieval of statements from Medline we have developed EBIMed, a service that combines document retrieval with co-occurrence-based analysis of Medline abstracts. Upon keyword query, EBIMed retrieves the abstracts from EMBL-EBI's installation of Medline and filters for sentences that contain biomedical terminology maintained in public bioinformatics resources. The extracted sentences and terminology are used to generate an overview table on proteins, Gene Ontology (GO) annotations, drugs and species used in the same biological context. All terms in retrieved abstracts and extracted sentences are linked to their entries in biomedical databases. We assessed the quality of the identification of terms and relations in the retrieved sentences. More than 90% of the protein names found indeed represented a protein. According to the analysis of four protein--protein pairs from the Wnt pathway we estimated that 37% of the statements containing such a pair mentioned a meaningful interaction and clarified the interaction of Dkk with LRP. We conclude that EBIMed improves access to information where proteins and drugs are involved in the same biological process, e.g. statements with GO annotations of proteins, protein--protein interactions and effects of drugs on proteins.

Availability: Available at http://www.ebi.ac.uk/Rebholz-srv/ebimed

Supplementary Data: Supplementary Data are available at Bioinformatics online.

Contact: [email protected]

/pdf/ebimed-text-crunching-to-gather-facts-for-proteins-from-kzc5usqeo8.pdf

EBIMed---text crunching to gather facts for proteins from Medline

This paper describes the databases and services of the European Bioinformatics Institute (EBI). In collaboration with DDBJ and GenBank/NCBI, the EBI maintains and distributes the EMBL Nucleotide Sequence Database, Europe's primary nucleotide sequence data resource. The EBI also maintains and distributes the SWISS-PROT Protein Sequence Database, in collaboration with Amos Bairoch of the University of Geneva. Over thirty additional specialist molecular biology databases, as well as software and documentation of interest to molecular biologists, are also available. The EBI network services include database searching, entry retrieval, and sequence similarity searching facilities.

Peter Stoehr

Papers

The EMBL Nucleotide Sequence Database

IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex

IPD - The Immuno-Polymorphism Database

EBIMed---text crunching to gather facts for proteins from Medline

The European Bioinformatics Institute (EBI) databases