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Henning Hermjakob

Publications and source records attributed to Henning Hermjakob.

34 records · Page 2Linked to original sources

PRIDE: the proteomics identifications database.

The advent of high-throughput proteomics has enabled the identification of ever increasing numbers of proteins. Correspondingly, the number of publications centered on these protein identifications has increased dramatically. With the first results of the HUPO Plasma Proteome Project being analyzed and many other large-scale proteomics projects about to disseminate their data, this trend is not likely to flatten out any time soon. However, the publication mechanism of these identified proteins has lagged behind in technical terms. Often very long lists of identifications are either published directly with the article, resulting in both a voluminous and rather tedious read, or are included on the publisher's website as supplementary information. In either case, these lists are typically only provided as portable document format documents with a custom-made layout, making it practically impossible for computer programs to interpret them, let alone efficiently query them. Here we propose the proteomics identifications (PRIDE) database (http://www.ebi.ac.uk/pride) as a means to finally turn publicly available data into publicly accessible data. PRIDE offers a web-based query interface, a user-friendly data upload facility, and a documented application programming interface for direct computational access. The complete PRIDE database, source code, data, and support tools are freely available for web access or download and local installation.

Computational Biology↗

Data management and preliminary data analysis in the pilot phase of the HUPO Plasma Proteome Project.

The pilot phase of the HUPO Plasma Proteome Project (PPP) is an international collaboration to catalog the protein composition of human blood plasma and serum by analyzing standardized aliquots of reference serum and plasma specimens using a variety of experimental techniques. Data management for this project included collection, integration, analysis, and dissemination of findings from participating organizations world-wide. Accomplishing this task required a communication and coordination infrastructure specific enough to support meaningful integration of results from all participants, but flexible enough to react to changing requirements and new insights gained during the course of the project and to allow participants with varying informatics capabilities to contribute. Challenges included integrating heterogeneous data, reducing redundant information to minimal identification sets, and data annotation. Our data integration workflow assembles a minimal and representative set of protein identifications, which account for the contributed data. It accommodates incomplete concordance of results from different laboratories, ambiguity and redundancy in contributed identifications, and redundancy in the protein sequence databases. Recommendations of the PPP for future large-scale proteomics endeavors are described.

Algorithms↗

Overview of the HUPO Plasma Proteome Project: results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-available database.

HUPO initiated the Plasma Proteome Project (PPP) in 2002. Its pilot phase has (1) evaluated advantages and limitations of many depletion, fractionation, and MS technology platforms; (2) compared PPP reference specimens of human serum and EDTA, heparin, and citrate-anti-coagulated plasma; and (3) created a publicly-available knowledge base (www.bioinformatics.med.umich.edu/hupo/ppp; www.ebi.ac.uk/pride). Thirty-five participating laboratories in 13 countries submitted datasets. Working groups addressed (a) specimen stability and protein concentrations; (b) protein identifications from 18 MS/MS datasets; (c) independent analyses from raw MS-MS spectra; (d) search engine performance, subproteome analyses, and biological insights; (e) antibody arrays; and (f) direct MS/SELDI analyses. MS-MS datasets had 15 710 different International Protein Index (IPI) protein IDs; our integration algorithm applied to multiple matches of peptide sequences yielded 9504 IPI proteins identified with one or more peptides and 3020 proteins identified with two or more peptides (the Core Dataset). These proteins have been characterized with Gene Ontology, InterPro, Novartis Atlas, OMIM, and immunoassay-based concentration determinations. The database permits examination of many other subsets, such as 1274 proteins identified with three or more peptides. Reverse protein to DNA matching identified proteins for 118 previously unidentified ORFs. We recommend use of plasma instead of serum, with EDTA (or citrate) for anticoagulation. To improve resolution, sensitivity and reproducibility of peptide identifications and protein matches, we recommend combinations of depletion, fractionation, and MS/MS technologies, with explicit criteria for evaluation of spectra, use of search algorithms, and integration of homologous protein matches. This Special Issue of PROTEOMICS presents papers integral to the collaborative analysis plus many reports of supplementary work on various aspects of the PPP workplan. These PPP results on complexity, dynamic range, incomplete sampling, false-positive matches, and integration of diverse datasets for plasma and serum proteins lay a foundation for development and validation of circulating protein biomarkers in health and disease.

Algorithms↗

Further steps in standardisation. Report of the second annual Proteomics Standards Initiative Spring Workshop (Siena, Italy 17-20th April 2005).

The spring workshop of the HUPO-PSI convened in Siena to further progress the data standards which are already making an impact on data exchange and deposition in the field of proteomics. Separate work groups pushed forward existing XML standards for the exchange of Molecular Interaction data (PSI-MI, MIF) and Mass Spectrometry data (PSI-MS, mzData) whilst significant progress was made on PSI-MS' mzIdent, which will allow the capture of data from analytical tools such as peak list search engines. A new focus for PSI (GPS, gel electrophoresis) was explored; as was the need for a common representation of protein modifications by all workers in the field of proteomics and beyond. All these efforts are contextualised by the work of the General Proteomics Standards workgroup; which in addition to the MIAPE reporting guidelines, is continually evolving an object model (PSI-OM) from which will be derived the general standard XML format for exchanging data between researchers, and for submission to repositories or journals.

Mass Spectrometry↗

Human Proteome Organisation Proteomics Standards Initiative. Pre-Congress Initiative.

The plenary session of the Proteomics Standards Initiative of the Human Proteome Organisation discussed the current status of the ongoing work in the fields of molecular interactions, mass spectrometry and the description of protein modifications. In addition, new areas are being opened up, 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 Functional Genomics Experiment efforts to define a general standard in which to encode data that will enable a systems biology approach to data analysis.

Databases, Genetic↗

The use of common ontologies and controlled vocabularies to enable data exchange and deposition for complex proteomic experiments.

Controlled vocabularies provide a roadmap through complex biological data. Proteomic data is increasing in volume and is currently poorly served by public repositories due to the large number of different formats in which the data is generated and stored. The Human Proteome Organization Proteome Standards Initiative is establishing standards for data transfer and deposition. These standards utilize ontologies and controlled vocabularies to describe experimental procedures and common processes such as sample preparation This paper will discuss the development of such ontologies by the user community and their current utilization in the fields of protein:proein interactions and mass spectrometry.

Computational Biology↗

IntAct: an open source molecular interaction database.

IntAct provides an open source database and toolkit for the storage, presentation and analysis of protein interactions. The web interface provides both textual and graphical representations of protein interactions, and allows exploring interaction networks in the context of the GO annotations of the interacting proteins. A web service allows direct computational access to retrieve interaction networks in XML format. IntAct currently contains approximately 2200 binary and complex interactions imported from the literature and curated in collaboration with the Swiss-Prot team, making intensive use of controlled vocabularies to ensure data consistency. All IntAct software, data and controlled vocabularies are available at http://www.ebi.ac.uk/intact.

Animals↗

Common interchange standards for proteomics data: Public availability of tools and schema.

The Proteomics Standards Initiative (PSI) aims to define community standards for data representation in proteomics and to facilitate data comparision, exchange and verification. To this end, a Level 1 Molecular Interaction XML data exchange format has been developed which has been accepted for publication and is freely available at the PSI website (http.//psidev.sf.net/). Several major protein interaction databases are already making data available in this format. A draft XML interchange format for mass spectrometry data has been written and is currently undergoing evaluation whilst work is ongoing to develop a proteomics data integration model, MIAPE.

Computational Biology↗

Advances in the development of common interchange standards for proteomic data.

The generation of proteomics data is increasingly high-throughput and high volume. Both experimental design and the technologies used to produce and subsequently analyze the data are becoming ever more complex. An increasing need for methods by which such data can be accurately described, stored and exchanged between experimenters and data repositories has been recognised. Work by the Proteomics Standards Initiative of the Human Proteome Organisation has laid the foundation for the development of standards by which experimental design can be described and data exchange facilitated. At a recent workshop in Nice, participants gathered to review the progress made to date and assist in pushing the process still further forward.

Humans↗

A common open representation of mass spectrometry data and its application to proteomics research.

A broad range of mass spectrometers are used in mass spectrometry (MS)-based proteomics research. Each type of instrument possesses a unique design, data system and performance specifications, resulting in strengths and weaknesses for different types of experiments. Unfortunately, the native binary data formats produced by each type of mass spectrometer also differ and are usually proprietary. The diverse, nontransparent nature of the data structure complicates the integration of new instruments into preexisting infrastructure, impedes the analysis, exchange, comparison and publication of results from different experiments and laboratories, and prevents the bioinformatics community from accessing data sets required for software development. Here, we introduce the 'mzXML' format, an open, generic XML (extensible markup language) representation of MS data. We have also developed an accompanying suite of supporting programs. We expect that this format will facilitate data management, interpretation and dissemination in proteomics research.

Database Management Systems↗

The HUPO PSI's molecular interaction format--a community standard for the representation of protein interaction data.

A major goal of proteomics is the complete description of the protein interaction network underlying cell physiology. A large number of small scale and, more recently, large-scale experiments have contributed to expanding our understanding of the nature of the interaction network. However, the necessary data integration across experiments is currently hampered by the fragmentation of publicly available protein interaction data, which exists in different formats in databases, on authors' websites or sometimes only in print publications. Here, we propose a community standard data model for the representation and exchange of protein interaction data. This data model has been jointly developed by members of the Proteomics Standards Initiative (PSI), a work group of the Human Proteome Organization (HUPO), and is supported by major protein interaction data providers, in particular the Biomolecular Interaction Network Database (BIND), Cellzome (Heidelberg, Germany), the Database of Interacting Proteins (DIP), Dana Farber Cancer Institute (Boston, MA, USA), the Human Protein Reference Database (HPRD), Hybrigenics (Paris, France), the European Bioinformatics Institute's (EMBL-EBI, Hinxton, UK) IntAct, the Molecular Interactions (MINT, Rome, Italy) database, the Protein-Protein Interaction Database (PPID, Edinburgh, UK) and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING, EMBL, Heidelberg, Germany).

Database Management Systems↗

Current status of proteomic standards development.

The generation of proteomic data is becoming ever more high throughput. Both the technologies and experimental designs used to generate and analyze data are becoming increasingly complex. The need for methods by which such data can be accurately described, stored and exchanged between experimenters and data repositories has been recognized. Work by the Proteome Standards Initiative of the Human Proteome Organization has laid the foundation for the development of standards by which experimental design can be described and data exchange facilitated. The Minimum Information About a Proteomic Experiment data model describes both the scope and purpose of a proteomics experiment and encompasses the development of more specific interchange formats such as the mzData model of mass spectrometry. The eXtensible Mark-up Language-MI data interchange format, which allows exchange of molecular interaction data, has already been published and major databases within this field are supplying data downloads in this format.

Databases, Protein↗

The proteomics standards initiative.

The Proteomics Standards Initiative (PSI) aims to define community standards for data representation in proteomics and to facilitate data comparison, exchange and verification. Progress has been made in the development of common standards for data exchange in the fields of both mass spectrometry and protein-protein interaction. A proteomics-specific extension is being created for the emerging American Society for Tests and Measurements mass spectrometry standard, which will be supported by manufacturers of both hardware and software. A data model for proteomics experimentation is under development and discussions on a public repository for published proteomics data are underway. The Protein-Protein Interactions group expects to publish the Level 1 PSI data exchange format for protein-protein interactions soon and discussions as to the content of Level 2 have been initiated.

Biochemistry↗

Further advances in the development of a data interchange standard for proteomics data.

The Protein Standards Initiative (PSI) aims to define community standards for data representation in proteomics and to facilitate data comparison, exchange and verification. Significant progress was made in advancing the design and implementation of a draft standard for exchanging experimental data from proteomics experiments involving mass spectrometry at the 51st Annual Conference of the American Society for Mass Spectrometry. In collaboration with the American Society for Tests and Measurements, the PSI propose to publish this first draft at the forthcoming HUPO 2nd World Congress in Montreal, 8-11 October 2003.

Computational Biology↗

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

The exponential increase in the submission of nucleotide sequences to the nucleotide sequence database by genome sequencing centres has resulted in a need for rapid, automatic methods for classification of the resulting protein sequences. There are several signature and sequence cluster-based methods for protein classification, each resource having distinct areas of optimum application owing to the differences in the underlying analysis methods. In recognition of this, InterPro was developed as an integrated documentation resource for protein families, domains and functional sites, to rationalise the complementary efforts of the individual protein signature database projects. The member databases - PRINTS, PROSITE, Pfam, ProDom, SMART and TIGRFAMs - form the InterPro core. Related signatures from each member database are unified into single InterPro entries. Each InterPro entry includes a unique accession number, functional descriptions and literature references, and links are made back to the relevant member database(s). Release 4.0 of InterPro (November 2001) contains 4,691 entries, representing 3,532 families, 1,068 domains, 74 repeats and 15 sites of post-translational modification (PTMs) encoded by different regular expressions, profiles, fingerprints and hidden Markov models (HMMs). Each InterPro entry lists all the matches against SWISS-PROT and TrEMBL (2,141,621 InterPro hits from 586,124 SWISS-PROT and TrEMBL protein sequences). The database is freely accessible for text- and sequence-based searches.

Algorithms↗