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Biomedical subjects

W Fleischmann

Publications and source records attributed to W Fleischmann.

At least 19 recordsLinked to original sources
PubMed2003

NEWT, a new taxonomy portal.

NEWT is a new taxonomy portal to the SWISS-PROT protein sequence knowledgebase. It contains taxonomy data, which is updated daily, for the complete set of species represented in SWISS-PROT, as well as those stored at the NCBI. Users can navigate through the taxonomy tree and access corresponding SWISS-PROT protein entries. In addition, a manually curated selection of external links allows access to specific information on selected species. NEWT is available at http://www.ebi.ac.uk/newt/.

Classification↗
PubMed2002

Interactive InterPro-based comparisons of proteins in whole genomes.

MOTIVATION: The SWISS-PROT group at the EBI has developed the Proteome Analysis Database utilizing existing resources and providing comprehensive and integrated comparative analysis of the predicted protein coding sequences of the complete genomes of bacteria, archaea and eukaryotes. The Proteome Analysis Database is accompanied by a program that has been designed to carry out interactive InterPro proteome comparisons for any one proteome against any other one or more of the proteomes in the database.

Computational Biology↗
PubMed2001

Functional annotation of a full-length mouse cDNA collection.

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Animals↗
PubMed2001

CluSTr: a database of clusters of SWISS-PROT+TrEMBL proteins.

The CluSTr (Clusters of SWISS-PROT and TrEMBL proteins) database offers an automatic classification of SWISS-PROT and TrEMBL proteins into groups of related proteins. The clustering is based on analysis of all pairwise comparisons between protein sequences. Analysis has been carried out for different levels of protein similarity, yielding a hierarchical organisation of clusters. The database provides links to InterPro, which integrates information on protein families, domains and functional sites from PROSITE, PRINTS, Pfam and ProDom. Links to the InterPro graphical interface allow users to see at a glance whether proteins from the cluster share particular functional sites. CluSTr also provides cross-references to HSSP and PDB. The database is available for querying and browsing at http://www.ebi.ac.uk/clustr.

Animals↗
PubMed2001

The InterPro database, an integrated documentation resource for protein families, domains and functional sites.

Signature databases are vital tools for identifying distant relationships in novel sequences and hence for inferring protein function. InterPro is an integrated documentation resource for protein families, domains and functional sites, which amalgamates the efforts of the PROSITE, PRINTS, Pfam and ProDom database projects. Each InterPro entry includes a functional description, annotation, literature references and links back to the relevant member database(s). Release 2.0 of InterPro (October 2000) contains over 3000 entries, representing families, domains, repeats and sites of post-translational modification encoded by a total of 6804 different regular expressions, profiles, fingerprints and Hidden Markov Models. Each InterPro entry lists all the matches against SWISS-PROT and TrEMBL (more than 1,000,000 hits from 462,500 proteins in SWISS-PROT and TrEMBL). The database is accessible for text- and sequence-based searches at http://www.ebi.ac.uk/interpro/. Questions can be emailed to interhelp@ebi.ac.uk.

Databases, Factual↗
PubMed2001

Proteome Analysis Database: online application of InterPro and CluSTr for the functional classification of proteins in whole genomes.

The SWISS-PROT group at EBI has developed the Proteome Analysis Database utilising existing resources and providing comparative analysis of the predicted protein coding sequences of the complete genomes of bacteria, archaea and eukaryotes (http://www.ebi.ac. uk/proteome/). The two main projects used, InterPro and CluSTr, give a new perspective on families, domains and sites and cover 31-67% (InterPro statistics) of the proteins from each of the complete genomes. CluSTr covers the three complete eukaryotic genomes and the incomplete human genome data. The Proteome Analysis Database is accompanied by a program that has been designed to carry out InterPro proteome comparisons for any one proteome against any other one or more of the proteomes in the database.

Animals↗
PubMed2001

Automatic rule generation for protein annotation with the C4.5 data mining algorithm applied on SWISS-PROT.

MOTIVATION: The gap between the amount of newly submitted protein data and reliable functional annotation in public databases is growing. Traditional manual annotation by literature curation and sequence analysis tools without the use of automated annotation systems is not able to keep up with the ever increasing quantity of data that is submitted. Automated supplements to manually curated databases such as TrEMBL or GenPept cover raw data but provide only limited annotation. To improve this situation automatic tools are needed that support manual annotation, automatically increase the amount of reliable information and help to detect inconsistencies in manually generated annotations. RESULTS: A standard data mining algorithm was successfully applied to gain knowledge about the Keyword annotation in SWISS-PROT. 11 306 rules were generated, which are provided in a database and can be applied to yet unannotated protein sequences and viewed using a web browser. They rely on the taxonomy of the organism, in which the protein was found and on signature matches of its sequence. The statistical evaluation of the generated rules by cross-validation suggests that by applying them on arbitrary proteins 33% of their keyword annotation can be generated with an error rate of 1.5%. The coverage rate of the keyword annotation can be increased to 60% by tolerating a higher error rate of 5%. AVAILABILITY: The results of the automatic data mining process can be browsed on http://golgi.ebi.ac.uk:8080/Spearmint/ Source code is available upon request. CONTACT: kretsch@ebi.ac.uk.

Algorithms↗
PubMed2000

The role SWISS-PROT and TrEMBL play in the genome research environment.

SWISS-PROT, a curated protein sequence data bank, contains not only sequence data but also annotation relevant to a particular sequence. The annotation added to each entry is done by a team of biologists and comes, primarily, from articles in journals reporting the actual sequencing and sometimes characterisation. Review articles and collaboration with external experts also play a role along with the use of secondary databases like PROSITE and Pfam in addition to a variety of feature prediction methods. Annotation added by these methods is checked for relevance and likelihood to a particular sequence. The onset of genome sequencing has led to a dramatic increase in sequence data to be included in SWISS-PROT. This has led to the production of TrEMBL (Translation of the EMBL database). TrEMBL consists of entries in a SWISS-PROT format that are derived from the translation of all coding sequences in the EMBL nucleotide sequence database, that are not in SWISS-PROT. Unlike SWISS-PROT entries those in TrEMBL are awaiting manual annotation. However, rather than just representing basic sequence and source information, steps have been taken to add features and annotation automatically. In taking these steps it is hoped that TrEMBL entries are enhanced with some indication as to what a protein is, could or may be.

Amino Acid Sequence↗
PubMed2000

The genome sequence of Drosophila melanogaster.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Animals↗
PubMed2000

Comparative genomics of the eukaryotes.

A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.

Animals↗
PubMed2000

InterPro--an integrated documentation resource for protein families, domains and functional sites.

MOTIVATION: InterPro is a new integrated documentation resource for protein families, domains and functional sites, developed initially as a means of rationalising the complementary efforts of the PROSITE, PRINTS, Pfam and ProDom database projects. RESULTS: Merged annotations from PRINTS, PROSITE and Pfam form the InterPro core. Each combined InterPro entry includes functional descriptions and literature references, and links are made back to the relevant parent database(s), allowing users to see at a glance whether a particular family or domain has associated patterns, profiles, fingerprints, etc. Merged and individual entries (i.e. those that have no counterpart in the companion resources) are assigned unique accession numbers. Release 1.2 of InterPro (June 2000) contains over 3000 entries, representing families, domains, repeats and sites of post-translational modification (PTMs) encoded by 6581 different regular expressions, profiles, fingerprints and Hidden Markov Models (HMMs). Each InterPro entry lists all the matches against SWISS-PROT and TrEMBL (more than 1000000 hits from 264333 different proteins out of 384572 in SWISS-PROT and TrEMBL).

Computational Biology↗
PubMed2000

Translocation of endotoxin and acute-phase proteins in malleolar fractures.

BACKGROUND AND OBJECTIVE: Translocation of endotoxins was demonstrated for multiple injury but not for minor trauma such as isolated malleolar fractures. Major trauma leads to substantial changes in the plasma concentration of acute-phase proteins. However, isolated malleolar fractures are minor trauma. The objective of this study was to elucidate the kinetics of endotoxemia and the ability of plasma to inactivate endotoxin of patients operated on malleolar fractures and to demonstrate the early time course of the acute-phase proteins C-reactive protein, transferrin, alpha1-acid glycoprotein, haptoglobin, and interleukin-6 and to correlate them with the amount of endotoxemia. METHODS: Thirty patients with malleolar fractures were operated on within 6 hours after injury. Blood was collected immediately after admission and regularly up to 96 hours after surgery. RESULTS: Preoperative endotoxin plasma levels were increased compared with that of healthy individuals (0.05 +/- 0.017 vs. 0.02 EU/mL). Endotoxemia peaked 0.5 hours after the surgical procedure at 0.096 +/- 0.03 (p < 0.05 vs. healthy) and decreased to almost normal values after 24 hours. The ability of the plasma to inactivate endotoxin was significantly reduced after the surgical procedure compared with normal subjects (recovery, 0.17 +/- 0.028 EU/mL vs. 0.04 +/- 0.01 EU/mL; p < 0.05). Plasma interleukin-6 peaked 0.5 hours postoperatively (114 +/- 11 pg/mL, p < 0.05 vs. healthy), decreasing thereafter. C-Reactive protein peaked at 45 +/- 5 mg/mL (p < 0.05) 48 hours after injury. Transferrin decreased significantly postoperatively (2.41 +/- 0.12 mg/mL vs. pre-OP 2.65 +/- 0.1 mg/mL) and remained on this level for 96 hours. Both, alpha1-acid glycoprotein and haptoglobin increased postoperatively until day 4 (0.78 +/- 0.06 mg/mL to 1.15 +/- 0.08 mg/mL and 1.51 +/- 0.12 mg/mL to 3.24 +/- 0.22 mg/mL). There was no correlation between endotoxemia and the concentrations of the acute-phase proteins and interleukin-6. CONCLUSION: Surgery for malleolar fractures is associated with temporary endotoxemia and temporary reduced endotoxin inactivation capacity of the plasma. The injury and the surgical procedure leads to substantial changes in the plasma concentrations of acute-phase proteins. The relation between endotoxemia and acute-phase response is not dose dependent.

Acute-Phase Proteins↗
PubMed1999

[Biosurgery - maggots, are they really the better surgeons?].

Between 1 October 1996 and 31 December 1998 123 patients (74 men, 43 women) suffering from acute (n = 17) and chronic (n = 21) infections and chronic wounds (n = 85) were treated with sterile maggots (Lucilia sericata). In most patients the indication for the use of maggots was a failure to respond to standard therapy. Healing occurred in all patients with acute infections, and chronic infections showed excellent short-term results. In chronic wounds disturbances of healing in diabetics responded best to maggot therapy, the etiologically inhomogeneous group of leg ulcers asked for a polypragmatic approach, and the worst results were seen in chronic arterial occlusive disease (stage 4). Our limited experience with "biosurgery", biased selection of patients, and lack of late results reduce the significance of our data; nevertheless, sterile maggots seem to be an astonishingly workable tool for solving problems in surgical wound treatment.

Acute Disease↗
PubMed1999

EDITtoTrEMBL: a distributed approach to high-quality automated protein sequence annotation.

SUMMARY: Many databases in molecular biology face the problem that the ever increasing rate of data production can no longer be handled by traditional methods, especially human curation. Therefore, a number of projects are currently investigating methods for automated sequence annotation. This paper describes the EBI's approach to this problem for protein sequences by integration of arbitrary analysis programs into a distributed and highly flexible environment. Our software framework allows an individual treatment of sequences depending on their particular properties, which is achieved through a high-level description of the preconditions and capabilities of analysing modules. This not only improves the overall performance of the annotation process, as unnecessary steps are avoided, but also enhances its quality since dependencies between different modules are taken into account. We have implemented a prototype and use it in the production of TrEMBL releases. AVAILABILITY: Upon request.

Algorithms↗
PubMed1999

A novel method for automatic functional annotation of proteins.

MOTIVATION: To cope with the increasing amount of sequence data, reliable automatic annotation tools are required. The TrEMBL database contains together with SWISS-PROT nearly all publicly available protein sequences, but in contrast to SWISS-PROT only limited functional annotation. To improve this situation, we had to develop a method of automatic annotation that produces highly reliable functional prediction using the language and the syntax of SWISS-PROT. RESULTS: An algorithm was developed and successfully used for the automatic annotation of a testset of unknown proteins. The predicted information included description, function, catalytic activity, cofactors, pathway, subcellular location, quaternary structure, similarity to other protein, active sites, and keywords. The algorithm showed a low coverage (10%), but a high specificity and reliability. AVAILABILITY: The results can be obtained by anonymous ftp from ftp.ebi.ac.uk/pub/databases/sp_tr_nrdb. The source code is available on request from the authors.

Algorithms↗
PubMed1999

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

UNLABELLED: 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

Databases, Factual↗
PubMed1999

[The BMW (biosurgical mechanical wound treatment) in diabetic foot].

The BMW-concept (Biosurgical-Mechanical-Wound treatment) is a effective supplement of already existing options of wound treatment. Based on the established principles of septic surgery vacuum sealing, instillation vacuum sealing and the application of sterile maggots optimize the treatment of diabetic foot ulcers, reduce time of treatment and offers a high comfort to the patient.

Amputation, Surgical↗