Philip Jones

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

PRIDE, the ‘PRoteomics IDEntifications database’ () 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.

BioMart Central Portal: an open database network for the biological community

BioMart Central Portal is a first of its kind, community-driven effort to provide unified access to dozens of biological databases spanning genomics, proteomics, model organisms, cancer data, ontology information and more. Anybody can contribute an independently maintained resource to the Central Portal, allowing it to be exposed to and shared with the research community, and linking it with the other resources in the portal. Users can take advantage of the common interface to quickly utilize different sources without learning a new system for each. The system also simplifies cross-database searches that might otherwise require several complicated steps. Several integrated tools streamline common tasks, such as converting between ID formats and retrieving sequences. The combination of a wide variety of databases, an easy-to-use interface, robust programmatic access and the array of tools make Central Portal a one-stop shop for biological data querying. Here, we describe the structure of Central Portal and show example queries to demonstrate its capabilities. Database URL: http://central.biomart.org.

PRIDE: new developments and new datasets

The PRIDE (http://www.ebi.ac.uk/pride) database of protein and peptide identifications was previously described in the NAR Database Special Edition in 2006. Since this publication, the volume of public data in the PRIDE relational database has increased by more than an order of magnitude. Several significant public datasets have been added, including identifications and processed mass spectra generated by the HUPO Brain Proteome Project and the HUPO Liver Proteome Project. The PRIDE software development team has made several significant changes and additions to the user interface and tool set associated with PRIDE. The focus of these changes has been to facilitate the submission process and to improve the mechanisms by which PRIDE can be queried. The PRIDE team has developed a Microsoft Excel workbook that allows the required data to be collated in a series of relatively simple spreadsheets, with automatic generation of PRIDE XML at the end of the process. The ability to query PRIDE has been augmented by the addition of a BioMart interface allowing complex queries to be constructed. Collaboration with groups outside the EBI has been fruitful in extending PRIDE, including an approach to encode iTRAQ quantitative data in PRIDE XML.

The Protein Identifier Cross-Referencing (PICR) service: reconciling protein identifiers across multiple source databases

BackgroundEach major protein database uses its own conventions when assigning protein identifiers. Resolving the various, potentially unstable, identifiers that refer to identical proteins is a major challenge. This is a common problem when attempting to unify datasets that have been annotated with proteins from multiple data sources or querying data providers with one flavour of protein identifiers when the source database uses another. Partial solutions for protein identifier mapping exist but they are limited to specific species or techniques and to a very small number of databases. As a result, we have not found a solution that is generic enough and broad enough in mapping scope to suit our needs.ResultsWe have created the Protein Identifier Cross-Reference (PICR) service, a web application that provides interactive and programmatic (SOAP and REST) access to a mapping algorithm that uses the UniProt Archive (UniParc) as a data warehouse to offer protein cross-references based on 100% sequence identity to proteins from over 70 distinct source databases loaded into UniParc. Mappings can be limited by source database, taxonomic ID and activity status in the source database. Users can copy/paste or upload files containing protein identifiers or sequences in FASTA format to obtain mappings using the interactive interface. Search results can be viewed in simple or detailed HTML tables or downloaded as comma-separated values (CSV) or Microsoft Excel (XLS) files suitable for use in a local database or a spreadsheet. Alternatively, a SOAP interface is available to integrate PICR functionality in other applications, as is a lightweight REST interface.ConclusionWe offer a publicly available service that can interactively map protein identifiers and protein sequences to the majority of commonly used protein databases. Programmatic access is available through a standards-compliant SOAP interface or a lightweight REST interface. The PICR interface, documentation and code examples are available at http://www.ebi.ac.uk/Tools/picr.

Integrating biological data – the Distributed Annotation System

BackgroundThe Distributed Annotation System (DAS) is a widely adopted protocol for dynamically integrating a wide range of biological data from geographically diverse sources. DAS continues to expand its applicability and evolve in response to new challenges facing integrative bioinformatics.ResultsHere we describe the various infrastructure components of DAS and present a new extended version of the DAS specification. Version 1.53E incorporates several recent developments, including its extension to serve new data types and an ontology for protein features.ConclusionOur extensions to the DAS protocol have facilitated the integration of new data types, and our improvements to the existing DAS infrastructure have addressed recent challenges. The steadily increasing numbers of available data sources demonstrates further adoption of the DAS protocol.

EBI metagenomics—a new resource for the analysis and archiving of metagenomic data

Metagenomics is a relatively recently established but rapidly expanding field that uses high-throughput next-generation sequencing technologies to characterize the microbial communities inhabiting different ecosystems (including oceans, lakes, soil, tundra, plants and body sites). Metagenomics brings with it a number of challenges, including the management, analysis, storage and sharing of data. In response to these challenges, we have developed a new metagenomics resource (http://www.ebi.ac.uk/metagenomics/) that allows users to easily submit raw nucleotide reads for functional and taxonomic analysis by a state-of-the-art pipeline, and have them automatically stored (together with descriptive, standards-compliant metadata) in the European Nucleotide Archive.

The Ontology Lookup Service: more data and better tools for controlled vocabulary queries

The Ontology Lookup Service (OLS) (http://www.ebi.ac.uk/ols) provides interactive and programmatic interfaces to query, browse and navigate an ever increasing number of biomedical ontologies and controlled vocabularies. The volume of data available for querying has more than quadrupled since it went into production and OLS functionality has been integrated into several high-usage databases and data entry tools. Improvements have been made to both OLS query interfaces, based on user feedback and requirements, to improve usability and service interoperability and provide novel ways to perform queries.

Perioperative Aspirin and Clonidine and Risk of Acute Kidney Injury A Randomized Clinical Trial

IMPORTANCEnAcute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm.nnnOBJECTIVEnTo determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury.nnnDESIGN, SETTING, AND PARTICIPANTSnA 2u2009×u20092 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013.nnnINTERVENTIONSnPatients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery.nnnMAIN OUTCOMES AND MEASURESnAcute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 μmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery.nnnRESULTSnAspirin (nu2009=u20093443) vs placebo (nu2009=u20093462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (nu2009=u20093453) vs placebo (nu2009=u20093452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58).nnnCONCLUSIONS AND RELEVANCEnAmong patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT01082874.

Bioinformatics training: a review of challenges, actions and support requirements

As bioinformatics becomes increasingly central to research in the molecular life sciences, the need to train non-bioinformaticians to make the most of bioinformatics resources is growing. Here, we review the key challenges and pitfalls to providing effective training for users of bioinformatics services, and discuss successful training strategies shared by a diverse set of bioinformatics trainers. We also identify steps that trainers in bioinformatics could take together to advance the state of the art in current training practices. The ideas presented in this article derive from the first Trainer Networking Session held under the auspices of the EU-funded SLING Integrating Activity, which took place in November 2009.

Dasty and UniProt DAS: a perfect pair for protein feature visualization

In this study, we present two freely available and complementary Distributed Annotation System (DAS) resources: a DAS reference server that provides up-to-date sequence and annotation from UniProt, with additional feature links and database cross-references from InterPro and a DAS client implemented using Java and Macromedia Flash that is optimized for the display of protein features.