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The EMBL nucleotide sequence database.

The European Molecular Biology Laboratory (EMBL) Nucleotide Sequence Database (http://www.ebi.ac. uk/embl/index.html ) is maintained at the European Bioinformatics Institute (EBI) in an international collaboration with the DNA Data Bank of Japan (DDBJ) and GenBank (USA). Data is exchanged amongst the collaborative databases on a daily basis. The major contributors to the EMBL database are individual authors and genome project groups. WEBIN is the preferred web-based submission system for individual submitters, whilst automatic procedures allow incorporation of sequence data from large-scale genome sequencing centres and from the European Patent Office (EPO). Database releases are produced quarterly. Network services allow free access to the most up-to-date data collection via Internet and WWW interfaces. 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) are available which allow external users to compare their own sequences against the most currently available data in the EMBL Nucleotide Sequence Database and SWISS-PROT.

Classification↗

Acupuncture for acute stroke.

BACKGROUND: Acupuncture-like sensory stimulation activates multiple efferent (nerve) pathways leading to altered activity in numerous neural systems. Acupuncture is widely accepted by Chinese people and it is increasingly requested by patients and their relatives in Western countries. OBJECTIVES: To assess the effectiveness and safety of acupuncture in patients with acute stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched August 2003), the Chinese Stroke Trials Register (August 2003) and the Chinese Acupuncture Trials Register (August 2003). Electronic searches were performed in the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), Alternative Medicine Database (1985 to 2003), CINAHL (1982 to 2003) and the Chinese Biological Medicine Database (1981 to 2003). Reference lists of systematic reviews and identified trials were handsearched. SELECTION CRITERIA: Randomised and quasi-randomised trials of acupuncture started within 30 days of stroke onset, compared with placebo/sham acupuncture or open control in patients with acute ischaemic and/or haemorrhagic stroke. Needling into skin was required for acupuncture. DATA COLLECTION AND ANALYSIS: Two reviewers selected trials for inclusion, assessed trial quality, and extracted the data independently. Authors of trials were contacted for missing data. MAIN RESULTS: Fourteen trials involving 1208 patients were included. Ten trials included patients with only ischaemic stroke. When acupuncture was compared with sham acupuncture or open control, there was a borderline significant trend towards fewer patients being dead or dependent (Odds ratio (OR) 0.66, 95% confidence interval (CI) 0.43 to 0.99), and significantly fewer being dead or needing institutional care (OR 0.58, 95% CI 0.35 to 0.96) in the acupuncture group after three months or more. There was also a significant difference favouring acupuncture in the mean change of global neurological deficit score during the treatment period (standardized mean difference (SMD) 1.17, 95% CI 0.30 to 2.04). Comparison of acupuncture with sham acupuncture only showed a statistically significant difference on death or requiring institutional care (OR 0.49, 95% CI 0.25 to 0.96), but not on death or dependency (OR 0.67, 95% CI 0.40 to 1.12), or change of global neurological deficit score (SMD 0.01, 95% CI -0.55 to 0.57). Severe adverse events with acupuncture (dizziness, intolerable pain and infection of acupoints) were rare (6/386, 1.55%). AUTHORS' CONCLUSIONS: Acupuncture appeared to be safe but without clear evidence of benefit. The number of patients is too small to be certain whether acupuncture is effective for treatment of acute ischaemic or haemorrhagic stroke. Larger, methodologically-sound trials are required.

Acupuncture Therapy↗

The Mouse Genome Database (MGD): from genes to mice--a community resource for mouse biology.

The Mouse Genome Database (MGD) forms the core of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a model organism database resource for the laboratory mouse. MGD provides essential integration of experimental knowledge for the mouse system with information annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genotype (sequence) through phenotype information, including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships among genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent improvements in MGD discussed here include the enhancement of phenotype resources, the re-development of the International Mouse Strain Resource, IMSR, the update of mammalian orthology datasets and the electronic publication of classic books in mouse genetics.

Animals↗

Re-analysis of data and its integration.

To understand a biological process it is clear that a single approach will not be sufficient, just like a single measurement on a protein--such as its expression level--does not describe protein function. Using reference sets of proteins as benchmarks different approaches can be scaled and integrated. Here, we demonstrate the power of data re-analysis and integration by applying it in a case study to data from deletion phenotype screens and mRNA expression profiling.

Computational Biology↗

Depositing electron microscopy maps.

A meeting was held at the European Bioinformatics Institute (EBI) in Hinxton, United Kingdom to discuss recent progress in the development of EMD, a database for maps determined by electron microscopy that is now integrated with MSD, the macromolecular structure database at EBI. This meeting of representatives of many of the major image processing groups in electron microscopy also discussed possible software developments that would ease the documentation and deposition of such datasets. The meeting concluded with a strong endorsement of map deposition in electron microscopy and its linkage with the family of archival databases in biomedical research.

Computational Biology↗

Prediction of physical protein-protein interactions.

Many essential cellular processes such as signal transduction, transport, cellular motion and most regulatory mechanisms are mediated by protein-protein interactions. In recent years, new experimental techniques have been developed to discover the protein-protein interaction networks of several organisms. However, the accuracy and coverage of these techniques have proven to be limited, and computational approaches remain essential both to assist in the design and validation of experimental studies and for the prediction of interaction partners and detailed structures of protein complexes. Here, we provide a critical overview of existing structure-independent and structure-based computational methods. Although these techniques have significantly advanced in the past few years, we find that most of them are still in their infancy. We also provide an overview of experimental techniques for the detection of protein-protein interactions. Although the developments are promising, false positive and false negative results are common, and reliable detection is possible only by taking a consensus of different experimental approaches. The shortcomings of experimental techniques affect both the further development and the fair evaluation of computational prediction methods. For an adequate comparative evaluation of prediction and high-throughput experimental methods, an appropriately large benchmark set of biophysically characterized protein complexes would be needed, but is sorely lacking.

Algorithms↗

Recurrent use of evolutionary importance for functional annotation of proteins based on local structural similarity.

The annotation of protein function has not kept pace with the exponential growth of raw sequence and structure data. An emerging solution to this problem is to identify 3D motifs or templates in protein structures that are necessary and sufficient determinants of function. Here, we demonstrate the recurrent use of evolutionary trace information to construct such 3D templates for enzymes, search for them in other structures, and distinguish true from spurious matches. Serine protease templates built from evolutionarily important residues distinguish between proteases and other proteins nearly as well as the classic Ser-His-Asp catalytic triad. In 53 enzymes spanning 33 distinct functions, an automated pipeline identifies functionally related proteins with an average positive predictive power of 62%, including correct matches to proteins with the same function but with low sequence identity (the average identity for some templates is only 17%). Although these template building, searching, and match classification strategies are not yet optimized, their sequential implementation demonstrates a functional annotation pipeline which does not require experimental information, but only local molecular mimicry among a small number of evolutionarily important residues.

Algorithms↗

Ten years of predictions ... and counting.

The CASP experiment has been run every other year since 1994. Its objective is to subject the available structure prediction methods to a blind test. This is a short report of the highlights of its last edition. 'Men who wish to know about the world must learn about it in its particular details' (Heraclitus of Ephesus, 535-475 bc).

Computational Biology↗

Mitoproteome: human heart mitochondrial protein sequence database.

The human mitochondrial proteome database has been developed by deriving data from a combination of public repositories and experimental and computational prediction methods. The experimental data is derived from highly purified mitochondria from human heart tissue, whereas predictions have been performed by MITOPRED, a genome-scale method for the prediction of nucleus-encoded mitochondrial proteins. Mitochondrial protein sequences from different sources have been clustered to generate a nonredundant dataset. Annotations related to the protein function, structure, disease association, pathways, and so on are collected from a number of public databases using commonly used UNIX and Perl scripts. This chapter provides a detailed description of various data sources and methods used to download, curate, parse, and generate meaningful annotations from primary as well as derived databases.

Computational Biology↗

Evaluation of echinacea for treatment of the common cold.

Considered to have immunostimulating activity, echinacea is a widely used phytomedicinal for treatment of the common cold and upper respiratory tract infections (URTIs). We reviewed the literature from the MEDLINE database (January 1966-July 1999), International Pharmaceutical Abstracts (IPA) online database, Cambridge Scientific Abstracts Biological Sciences online database, Alt-Health Watch online database, EMBase CD-ROM database, and references from published articles, reviews, and letters to evaluate evidence from clinical trials of echinacea's purported efficacy for treating or preventing URTIs. Twelve clinical studies published from 1961-1997 concluded that echinacea was efficacious for treating the common cold, but the results are unclear due to inherent flaws in study design. Five trials were published since 1997; two showed that echinacea lacked efficacy for treating and preventing URTI symptoms, and three concluded that it was effective in reducing the frequency, duration, and severity of common cold symptoms. Again, these results are unclear because of methodologic uncertainties, such as small populations and use of noncommercially available, nonstandardized dosage forms. Although evidence for echinacea's efficacy is inconclusive, it appears to be safe. Patients without contraindications to it may not be dissuaded from using an appropriate preparation to treat the common cold.

Clinical Trials as Topic↗

SWISS-PROT: connecting biomolecular knowledge via a protein database.

With the explosive growth of biological data, the development of new means of data storage was needed. More and more often biological information is no longer published in the conventional way via a publication in a scientific journal, but only deposited into a database. In the last two decades these databases have become essential tools for researchers in biological sciences. Biological databases can be classified according to the type of information they contain. There are basically three types of sequence-related databases (nucleic acid sequences, protein sequences and protein tertiary structures) as well as various specialized data collections. It is important to provide the users of biomolecular databases with a degree of integration between these databases as by nature all of these databases are connected in a scientific sense and each one of them is an important piece to biological complexity. In this review we will highlight our effort in connecting biological information as demonstrated in the SWISS-PROT protein database.

Amino Acid Sequence↗