Biomedical subjects

Rolf Apweiler

Publications and source records attributed to Rolf Apweiler.

At least 19 recordsLinked to original sources

PubMed2007

Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana.

We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is approximately 32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene.

Arabidopsis↗

PubMed2007

New developments in the InterPro database.

InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). The InterProScan search tool is now also available via a web service at http://www.ebi.ac.uk/Tools/webservices/WSInterProScan.html.

Databases, Protein↗

PubMed2007

Proteomic data exchange and storage: the need for common standards and public repositories.

The ever increasing volumes of proteomic data now being produced by laboratories across the world have resulted in major issues in data storage and accessibility. The further demands of multilaboratory initiatives has highlighted issues when collaborators cannot import data generated within the same project but generated by different hardware types and processed by laboratory-specific work flows and analyses packages. There is an increasing need for common data standards that will allow the interchange of data between different instrumentation, search engines, and between laboratory databases. This could then lead to the establishment of data repositories from where benchmark datasets could be accessed and reanalyzed. The Human Proteome Organization is currently supporting efforts to establish such standards. The work of the Proteomics Standards Initiative has lead to the development of the mzData XML interchange standard and is now broadening its scope to produce a spectral analysis output format, mzIdent. Accompanying controlled vocabularies allow the accurate, while systematic, representation of metadata throughout both schema.

Benchmarking↗

PubMed2006

GOAnnotator: linking protein GO annotations to evidence text.

BACKGROUND: Annotation of proteins with gene ontology (GO) terms is ongoing work and a complex task. Manual GO annotation is precise and precious, but it is time-consuming. Therefore, instead of curated annotations most of the proteins come with uncurated annotations, which have been generated automatically. Text-mining systems that use literature for automatic annotation have been proposed but they do not satisfy the high quality expectations of curators. RESULTS: In this paper we describe an approach that links uncurated annotations to text extracted from literature. The selection of the text is based on the similarity of the text to the term from the uncurated annotation. Besides substantiating the uncurated annotations, the extracted texts also lead to novel annotations. In addition, the approach uses the GO hierarchy to achieve high precision. Our approach is integrated into GOAnnotator, a tool that assists the curation process for GO annotation of UniProt proteins. CONCLUSION: The GO curators assessed GOAnnotator with a set of 66 distinct UniProt/SwissProt proteins with uncurated annotations. GOAnnotator provided correct evidence text at 93% precision. This high precision results from using the GO hierarchy to only select GO terms similar to GO terms from uncurated annotations in GOA. Our approach is the first one to achieve high precision, which is crucial for the efficient support of GO curators. GOAnnotator was implemented as a web tool that is freely available at http://xldb.di.fc.ul.pt/rebil/tools/goa/.

Journal Article↗

PubMed2006

EMBL Nucleotide Sequence Database in 2006.

The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl) at the EMBL European Bioinformatics Institute, UK, offers a large and freely accessible collection of nucleotide sequences and accompanying annotation. The database is maintained in collaboration with DDBJ and GenBank. Data are exchanged between the collaborating databases on a daily basis to achieve optimal synchrony. Webin is the preferred tool for individual submissions of nucleotide sequences, including Third Party Annotation, alignments and bulk data. Automated procedures are provided for submissions from large-scale sequencing projects and data from the European Patent Office. In 2006, the volume of data has continued to grow exponentially. Access to the data is provided via SRS, ftp and variety of other methods. Extensive external and internal cross-references enable users to search for related information across other databases and within the database. All available resources can be accessed via the EBI home page at http://www.ebi.ac.uk/. Changes over the past year include changes to the file format, further development of the EMBLCDS dataset and developments to the XML format.

Base Sequence↗

PubMed2006

Annotating the human proteome: beyond establishing a parts list.

The completion of the human genome has shifted the attention from deciphering the sequence to the identification and characterisation of the functional components, including genes. Improved gene prediction algorithms, together with the existing transcript and protein information, have enabled the identification of most exons in a genome. Availability of the 'parts list' has fostered the development of experimental approaches to systematically interrogate gene function on the genome, transcriptome and proteome level. Studying gene function at the protein level is vital to the understanding of how cells perform their functions as variations in protein isoforms and protein quantity which may underlie a change in phenotype can often not be deduced from sequence or transcript level genomics experiments alone. Recent advancements in proteomics have afforded technologies capable of measuring protein expression, post-translational modifications of these proteins, their subcellular localisation and assembly into complexes and pathways. Although an enormous amount of data already exists on the function of many human proteins, much of it is scattered over multiple resources. Public domain databases are therefore required to manage and collate this information and present it to the user community in both a human and machine readable manner. Of special importance here is the integration of heterogeneous data to facilitate the creation of resources that go beyond a mere parts list.

Humans↗

PubMed2006

Bioinformatics database infrastructure for biotechnology research.

Many databases are available that provide valuable data resources for the biotechnological researcher. According to their core data, they can be divided into different types. Some databases provide primary data, like all published nucleotide sequences, others deal with protein sequences. In addition to these two basic types of databases, a huge number of more specialized resources are available, like databases about protein structures, protein identification, special features of genes and/or proteins, or certain organisms. Furthermore, some resources offer integrated views on different types of data, allowing the user to do easy customized queries over large datasets and to compare different types of data.

Animals↗

PubMed2006

UniSave: the UniProtKB sequence/annotation version database.

SUMMARY: The UniProtKB Sequence/Annotation Version database (UniSave) is a comprehensive archive of UniProtKB/Swiss-Prot and UniProtKB/TrEMBL entry versions. All changed Swiss-Prot and TrEMBL entries are loaded into the UniSave as part of the public bi-weekly UniProtKB releases. Unlike the UniProtKB, which contains only the latest Swiss-Prot and TrEMBL entry versions, the UniSave provides access to previous versions of these entries. AVAILABILITY: http://www.ebi.ac.uk/uniprot/unisave

Database Management Systems↗

PubMed2006

The Ontology Lookup Service, a lightweight cross-platform tool for controlled vocabulary queries.

BACKGROUND: With the vast amounts of biomedical data being generated by high-throughput analysis methods, controlled vocabularies and ontologies are becoming increasingly important to annotate units of information for ease of search and retrieval. Each scientific community tends to create its own locally available ontology. The interfaces to query these ontologies tend to vary from group to group. We saw the need for a centralized location to perform controlled vocabulary queries that would offer both a lightweight web-accessible user interface as well as a consistent, unified SOAP interface for automated queries. RESULTS: The Ontology Lookup Service (OLS) was created to integrate publicly available biomedical ontologies into a single database. All modified ontologies are updated daily. A list of currently loaded ontologies is available online. The database can be queried to obtain information on a single term or to browse a complete ontology using AJAX. Auto-completion provides a user-friendly search mechanism. An AJAX-based ontology viewer is available to browse a complete ontology or subsets of it. A programmatic interface is available to query the webservice using SOAP. The service is described by a WSDL descriptor file available online. A sample Java client to connect to the webservice using SOAP is available for download from SourceForge. All OLS source code is publicly available under the open source Apache Licence. CONCLUSION: The OLS provides a user-friendly single entry point for publicly available ontologies in the Open Biomedical Ontology (OBO) format. It can be accessed interactively or programmatically at http://www.ebi.ac.uk/ontology-lookup/.

Database Management Systems↗

PubMed2006

EMBL Nucleotide Sequence Database: developments in 2005.

The EMBL Nucleotide Sequence Database (www.ebi.ac.uk/embl) at the EMBL European Bioinformatics Institute, UK, offers a comprehensive set of publicly available nucleotide sequence and annotation, freely accessible to all. Maintained in collaboration with partners DDBJ and GenBank, coverage includes whole genome sequencing project data, directly submitted sequence, sequence recorded in support of patent applications and much more. The database continues to offer submission tools, data retrieval facilities and user support. In 2005, the volume of data offered has continued to grow exponentially. In addition to the newly presented data, the database encompasses a range of new data types generated by novel technologies, offers enhanced presentation and searchability of the data and has greater integration with other data resources offered at the EBI and elsewhere. In stride with these developing data types, the database has continued to develop submission and retrieval tools to maximise the information content of submitted data and to offer the simplest possible submission routes for data producers. New developments, the submission process, data retrieval and access to support are presented in this paper, along with links to sources of further information.

Animals↗

PubMed2006

PRIDE: a public repository of protein and peptide identifications for the proteomics community.

PRIDE, the 'PRoteomics IDEntifications database' (http://www.ebi.ac.uk/pride) is a database of protein and peptide identifications that have been described in the scientific literature. These identifications will typically be from specific species, tissues and sub-cellular locations, perhaps under specific disease conditions. Any post-translational modifications that have been identified on individual peptides can be described. These identifications may be annotated with supporting mass spectra. At the time of writing, PRIDE includes the full set of identifications as submitted by individual laboratories participating in the HUPO Plasma Proteome Project and a profile of the human platelet proteome submitted by the University of Ghent in Belgium. By late 2005 PRIDE is expected to contain the identifications and spectra generated by the HUPO Brain Proteome Project. Proteomics laboratories are encouraged to submit their identifications and spectra to PRIDE to support their manuscript submissions to proteomics journals. Data can be submitted in PRIDE XML format if identifications are included or mzData format if the submitter is depositing mass spectra without identifications. PRIDE is a web application, so submission, searching and data retrieval can all be performed using an internet browser. PRIDE can be searched by experiment accession number, protein accession number, literature reference and sample parameters including species, tissue, sub-cellular location and disease state. Data can be retrieved as machine-readable PRIDE or mzData XML (the latter for mass spectra without identifications), or as human-readable HTML.

Databases, Protein↗

PubMed2006

The Universal Protein Resource (UniProt): an expanding universe of protein information.

The Universal Protein Resource (UniProt) provides a central resource on protein sequences and functional annotation with three database components, each addressing a key need in protein bioinformatics. The UniProt Knowledgebase (UniProtKB), comprising the manually annotated UniProtKB/Swiss-Prot section and the automatically annotated UniProtKB/TrEMBL section, is the preeminent storehouse of protein annotation. The extensive cross-references, functional and feature annotations and literature-based evidence attribution enable scientists to analyse proteins and query across databases. The UniProt Reference Clusters (UniRef) speed similarity searches via sequence space compression by merging sequences that are 100% (UniRef100), 90% (UniRef90) or 50% (UniRef50) identical. Finally, the UniProt Archive (UniParc) stores all publicly available protein sequences, containing the history of sequence data with links to the source databases. UniProt databases continue to grow in size and in availability of information. Recent and upcoming changes to database contents, formats, controlled vocabularies and services are described. New download availability includes all major releases of UniProtKB, sequence collections by taxonomic division and complete proteomes. A bibliography mapping service has been added, and an ID mapping service will be available soon. UniProt databases can be accessed online at http://www.uniprot.org or downloaded at ftp://ftp.uniprot.org/pub/databases/.

Databases, Protein↗

PubMed2006

Autumn 2005 Workshop of the Human Proteome Organisation Proteomics Standards Initiative (HUPO-PSI) Geneva, September, 4-6, 2005.

The autumn workshop of the Proteomics Standards Initiative of the Human Proteomics Organisation met to further advance the development of the existing standards in the fields of molecular interactions and mass spectrometry. In addition, new areas were addressed, in particular developing standards for the description and exchange of data from gel electrophoresis experiments. The General Proteomics Standards group is now working closely with the FuGE (Functional Genomics Experiment) efforts to define a general standard in which to encode data that will enable a systems biology approach to data analysis. Common to all these efforts is the field of protein modifications, and work has been initiated to establish an ontology in this field that can be used by both workers in the field of proteomics and the wider scientific community.

Databases, Protein↗

PubMed2006

The HUPO Brain Proteome Project jamboree: centralised summary of the pilot studies.

The Bioinformatics Committee of the HUPO Brain Proteome Project (HUPO BPP) meets regularly to execute the post-lab analyses of the data produced in the HUPO BPP pilot studies. On January 9-11, 2006 the members as well as invited analysts came together at the European Bioinformatics Institute in Hinxton, UK for the pilot studies jamboree. The results of the reprocessing were presented and tasks forces were initiated to compile, to interpret and to summarise the data obtained.

Animals↗

PubMed2006

Gaining knowledge from previously unexplained spectra-application of the PTM-Explorer software to detect PTM in HUPO BPP MS/MS data.

A novel software tool named PTM-Explorer has been applied to LC-MS/MS datasets acquired within the Human Proteome Organisation (HUPO) Brain Proteome Project (BPP). PTM-Explorer enables automatic identification of peptide MS/MS spectra that were not explained in typical sequence database searches. The main focus was detection of PTMs, but PTM-Explorer detects also unspecific peptide cleavage, mass measurement errors, experimental modifications, amino acid substitutions, transpeptidation products and unknown mass shifts. To avoid a combinatorial problem the search is restricted to a set of selected protein sequences, which stem from previous protein identifications using a common sequence database search. Prior to application to the HUPO BPP data, PTM-Explorer was evaluated on excellently manually characterized and evaluated LC-MS/MS data sets from Alpha-A-Crystallin gel spots obtained from mouse eye lens. Besides various PTMs including phosphorylation, a wealth of experimental modifications and unspecific cleavage products were successfully detected, completing the primary structure information of the measured proteins. Our results indicate that a large amount of MS/MS spectra that currently remain unidentified in standard database searches contain valuable information that can only be elucidated using suitable software tools.

Amino Acid Sequence↗

PubMed2006

Functional annotation of proteins identified in human brain during the HUPO Brain Proteome Project pilot study.

The HUPO Brain Proteome Project is an initiative coordinating proteomics studies to characterise human and mouse brain proteomes. Proteins identified in human brain samples during the project's pilot phase were put into biological context through integration with various annotation sources followed by a bioinformatics analysis. The data set was related to the genome sequence via the genes encoding identified proteins including an assessment of splice variant identification as well as an analysis of tissue specificity of the respective transcripts. Proteins were furthermore categorised according to subcellular localisation, molecular function and biological process, grouped into protein families and mapped to biological pathways they are known to act in. Involvement in pathological conditions was examined based on association with entries in the online version of Mendelian Inheritance in Man and an interaction network was derived from curated protein-proteininteraction data. Overall a non-redundant set of 1804 proteins was identified in human brain samples. In the majority of cases splice variants could be unambiguously identified by unique peptides, including matches to several hypothetical transcripts of known as well as predicted genes.

Alternative Splicing↗

PubMed2006

A comparison of the HUPO Brain Proteome Project pilot with other proteomics studies.

The pilot phase of the Brain Proteome Project (BPP), the Human Proteome Organization (HUPO) initiative that focuses on studies of the brain of both humans and mice, has now been completed. Participating laboratories studied the proteomes of two human samples derived from biopsy and autopsy as well as three mouse samples from various developmental stages. With the combined and centrally reprocessed data now available, a comparison in terms of protein identifications and project organization is made between the HUPO BPP pilot and three other proteomics studies: the HUPO Plasma Proteome Project (PPP) pilot, a proteome of human blood platelets and a recently published comprehensive mouse proteome. Finally, as any comparison between large-scale proteomics datasets is decidedly non-trivial, we also evaluate and discuss several ways to go about comparing such different result sets.

Animals↗

PubMed2006

Automated reprocessing pipeline for searching heterogeneous mass spectrometric data of the HUPO Brain Proteome Project pilot phase.

The newly available techniques for sensitive proteome analysis and the resulting amount of data require a new bioinformatics focus on automatic methods for spectrum reprocessing and peptide/protein validation. Manual validation of results in such studies is not feasible and objective enough for quality relevant interpretation. The necessity for tools enabling an automatic quality control is, therefore, important to produce reliable and comparable data in such big consortia as the Human Proteome Organization Brain Proteome Project. Standards and well-defined processing pipelines are important for these consortia. We show a way for choosing the right database model, through collecting data, processing these with a decoy database and end up with a quality controlled protein list merged from several search engines, including a known false-positive rate.

Algorithms↗