Protein kinase resource: an integrated environment for phosphorylation research

The protein kinase superfamily is an important group of enzymes controlling cellular signaling cascades. The increasing amount of available experimental data provides a foundation for deeper understanding of details of signaling systems and the underlying cellular processes. Here, we describe the Protein Kinase Resource, an integrated online service that provides access to information relevant to cell signaling and enables kinase researchers to visualize and analyze the data directly in an online environment. The data set is synchronized with Uniprot and Protein Data Bank (PDB) databases and is regularly updated and verified. Additional annotation includes interactive display of domain composition, cross-references between orthologs and functional mapping to OMIM records. The Protein Kinase Resource provides an integrated view of the protein kinase superfamily by linking data with their visual representation. Thus, human kinases can be mapped onto the human kinome tree via an interactive display. Sequence and structure data can be easily displayed using applications developed for the PKR and integrated with the website and the underlying database. Advanced search mechanisms, such as multiparameter lookup, sequence pattern, and blast search, enable fast access to the desired information, while statistics tools provide the ability to analyze the relationships among the kinases under study. The integration of data presentation and visualization implemented in the Protein Kinase Resource can be adapted by other online providers of scientific data and should become an effective way to access available experimental information.     

The protein information resource (PIR)

The Protein Information Resource (PIR) produces the largest, most comprehensive, annotated protein sequence database in the public domain, the PIR-International Protein Sequence Database, in collaboration with the Munich Information Center for Protein Sequences (MIPS) and the Japan International Protein Sequence Database (JIPID). The expanded PIR WWW site allows sequence similarity and text searching of the Protein Sequence Database and auxiliary databases. Several new web-based search engines combine searches of sequence similarity and database annotation to facilitate the analysis and functional identification of proteins. New capabilities for searching the PIR sequence databases include annotation-sorted search, domain search, combined global and domain search, and interactive text searches. The PIR-International databases and search tools are accessible on the PIR WWW site at http://pir.georgetown.edu and at the MIPS WWW site at http://www. mips.biochem.mpg.de. The PIR-International Protein Sequence Database and other files are also available by FTP.     

Dragon Plant Biology Explorer. A text-mining tool for integrating associations between genetic and biochemical entities with genome annotation and biochemical terms lists

We introduce a tool for text mining, Dragon Plant Biology Explorer (DPBE) that integrates information on Arabidopsis (Arabidopsis thaliana) genes with their functions, based on gene ontologies and biochemical entity vocabularies, and presents the associations as interactive networks. The associations are based on (1) user-provided PubMed abstracts; (2) a list of Arabidopsis genes compiled by The Arabidopsis Information Resource; (3) user-defined combinations of four vocabulary lists based on the ones developed by the general, plant, and Arabidopsis GO consortia; and (4) three lists developed here based on metabolic pathways, enzymes, and metabolites derived from AraCyc, BRENDA, and other metabolism databases. We demonstrate how various combinations can be applied to fields of (1) gene function and gene interaction analyses, (2) plant development, (3) biochemistry and metabolism, and (4) pharmacology of bioactive compounds. Furthermore, we show the suitability of DPBE for systems approaches by integration with "omics" platform outputs. Using a list of abiotic stress-related genes identified by microarray experiments, we show how this tool can be used to rapidly build an information base on the previously reported relationships. This tool complements the existing biological resources for systems biology by identifying potentially novel associations using text analysis between cellular entities based on genome annotation terms. Thus, it allows researchers to efficiently summarize existing information for a group of genes or pathways, so as to make better informed choices for designing validation experiments. Last, DPBE can be helpful for beginning researchers and graduate students to summarize vast information in an unfamiliar area. DPBE is freely available for academic and nonprofit users at http://research.i2r.a-star.edu.sg/DRAGON/ME2/.     

MIPS: a database for protein sequences and complete genomes.

The MIPS group [Munich Information Center for Protein Sequences of the German National Center for Environment and Health (GSF)] at the Max-Planck-Institute for Biochemistry, Martinsried near Munich, Germany, is involved in a number of data collection activities, including a comprehensive database of the yeast genome, a database reflecting the progress in sequencing the Arabidopsis thaliana genome, the systematic analysis of other small genomes and the collection of protein sequence data within the framework of the PIR-International Protein Sequence Database (described elsewhere in this volume). Through its WWW server (http://www.mips.biochem.mpg.de ) MIPS provides access to a variety of generic databases, including a database of protein families as well as automatically generated data by the systematic application of sequence analysis algorithms. The yeast genome sequence and its related information was also compiled on CD-ROM to provide dynamic interactive access to the 16 chromosomes of the first eukaryotic genome unraveled.     

Paper2sequences: retrieval of sequences listed in a publication

Our web-based tool simplifies the often laborious procedure of retrieving a set of biosequences in a publication or webpage. As a front-end to the Bioperl toolkit, it accepts as an input a list of identifiers. They are specified in an ASCII table (copy-pasted from the publication's PDF or HTML page) and give rise to queries in multiple databases for the protein/nucleic acid data specified. Currently, GenBank, PIR (Protein Information Resource) and Swiss-Prot are supported. For any sequence accession code listed, the database can be specified and, if retrieval fails, automatic lookup for the same code in other databases can be requested. Sequence length information (if specified) and heuristic rules are used to drive the lookup if multiple protein coding sequences (CDS) are part of a single accession. Warnings are issued in cases of ambiguities and inconsistencies. An advanced option enables the user to format the output in whatever format they wish.     

Protein Information Resource: a community resource for expert annotation of protein data

The Protein Information Resource, in collaboration with the Munich Information Center for Protein Sequences (MIPS) and the Japan International Protein Information Database (JIPID), produces the most comprehensive and expertly annotated protein sequence database in the public domain, the PIR-International Protein Sequence Database. To provide timely and high quality annotation and promote database interoperability, the PIR-International employs rule-based and classification-driven procedures based on controlled vocabulary and standard nomenclature and includes status tags to distinguish experimentally determined from predicted protein features. The database contains about 200,000 non-redundant protein sequences, which are classified into families and superfamilies and their domains and motifs identified. Entries are extensively cross-referenced to other sequence, classification, genome, structure and activity databases. The PIR web site features search engines that use sequence similarity and database annotation to facilitate the analysis and functional identification of proteins. The PIR-Inter-national databases and search tools are accessible on the PIR web site at http://pir.georgetown.edu/ and at the MIPS web site at http://www.mips.biochem.mpg.de. The PIR-International Protein Sequence Database and other files are also available by FTP.     

GeneCruiser: a web service for the annotation of microarray data

SUMMARY: GeneCruiser is a web service allowing users to annotate their genomic data by mapping microarray feature identifiers to gene identifiers from databases, such as UniGene, while providing links to web resources, such as the UCSC Genome Browser. It relies on a regularly updated database that retrieves and indexes the mappings between microarray probes and genomic databases. Genes are identified using the Life Sciences Identifier standard. AVAILABILITY: GeneCruiser is freely available in the following forms: Web service and Web application, http://www.genecruiser.org; GenePattern, GeneCruiser access has been integrated into our microarray analysis platform, GenePattern. http://www.genepattern.org.     

MIPS: a database for genomes and protein sequences

The Munich Information Center for Protein Sequences (MIPS-GSF), Martinsried, near Munich, Germany, continues its longstanding tradition to develop and maintain high quality curated genome databases. In addition, efforts have been intensified to cover the wealth of complete genome sequences in a systematic, comprehensive form. Bioinformatics, supporting national as well as European sequencing and functional analysis projects, has resulted in several up-to-date genome-oriented databases. This report describes growing databases reflecting the progress of sequencing the Arabidopsis thaliana (MATDB) and Neurospora crassa genomes (MNCDB), the yeast genome database (MYGD) extended by functional analysis data, the database of annotated human EST-clusters (HIB) and the database of the complete cDNA sequences from the DHGP (German Human Genome Project). It also contains information on the up-to-date database of complete genomes (PEDANT), the classification of protein sequences (ProtFam) and the collection of protein sequence data within the framework of the PIR-International Protein Sequence Database. These databases can be accessed through the MIPS WWW server (http://www. mips.biochem.mpg.de).     

AraCyc: a biochemical pathway database for Arabidopsis

AraCyc is a database containing biochemical pathways of Arabidopsis, developed at The Arabidopsis Information Resource (http://www.arabidopsis.org). The aim of AraCyc is to represent Arabidopsis metabolism as completely as possible with a user-friendly Web-based interface. It presently features more than 170 pathways that include information on compounds, intermediates, cofactors, reactions, genes, proteins, and protein subcellular locations. The database uses Pathway Tools software, which allows the users to visualize a bird's eye view of all pathways in the database down to the individual chemical structures of the compounds. The database was built using Pathway Tools' Pathologic module with MetaCyc, a collection of pathways from more than 150 species, as a reference database. This initial build was manually refined and annotated. More than 20 plant-specific pathways, including carotenoid, brassinosteroid, and gibberellin biosyntheses have been added from the literature. A list of more than 40 plant pathways will be added in the coming months. The quality of the initial, automatic build of the database was compared with the manually improved version, and with EcoCyc, an Escherichia coli database using the same software system that has been manually annotated for many years. In addition, a Perl interface, PerlCyc, was developed that allows programmers to access Pathway Tools databases from the popular Perl language. AraCyc is available at the tools section of The Arabidopsis Information Resource Web site (http://www.arabidopsis.org/tools/aracyc).     

FunRich proteomics software analysis,let the fun begin!

Protein MS analysis is the preferred method for unbiased protein identification. It is normally applied to a large number of both small‐scale and high‐throughput studies. However, user‐friendly computational tools for protein analysis are still needed. In this issue, Mathivanan and colleagues (Proteomics 2015, 15, 2597–2601) report the development of FunRich software, an open‐access software that facilitates the analysis of proteomics data, providing tools for functional enrichment and interaction network analysis of genes and proteins. FunRich is a reinterpretation of proteomic software, a standalone tool combining ease of use with customizable databases, free access, and graphical representations.     

MOET: a web-based gene set enrichment tool at the Rat Genome Database for multiontology and multispecies analyses

Biological interpretation of a large amount of gene or protein data is complex. Ontology analysis tools are imperative in finding functional similarities through overrepresentation or enrichment of terms associated with the input gene or protein lists. However, most tools are limited by their ability to do ontology-specific and species-limited analyses. Furthermore, some enrichment tools are not updated frequently with recent information from databases, thus giving users inaccurate, outdated or uninformative data. Here, we present MOET or the Multi-Ontology Enrichment Tool (v.1 released in April 2019 and v.2 released in May 2021), an ontology analysis tool leveraging data that the Rat Genome Database (RGD) integrated from in-house expert curation and external databases including the National Center for Biotechnology Information (NCBI), Mouse Genome Informatics (MGI), The Kyoto Encyclopedia of Genes and Genomes (KEGG), The Gene Ontology Resource, UniProt-GOA, and others. Given a gene or protein list, MOET analysis identifies significantly overrepresented ontology terms using a hypergeometric test and provides nominal and Bonferroni corrected P-values and odds ratios for the overrepresented terms. The results are shown as a downloadable list of terms with and without Bonferroni correction, and a graph of the P-values and number of annotated genes for each term in the list. MOET can be accessed freely from https://rgd.mcw.edu/rgdweb/enrichment/start.html.     

The Arabidopsis Information Resource (TAIR): a comprehensive database and web-based information retrieval, analysis, and visualization system for a model plant

Arabidopsis thaliana, a small annual plant belonging to the mustard family, is the subject of study by an estimated 7000 researchers around the world. In addition to the large body of genetic, physiological and biochemical data gathered for this plant, it will be the first higher plant genome to be completely sequenced, with completion expected at the end of the year 2000. The sequencing effort has been coordinated by an international collaboration, the Arabidopsis Genome Initiative (AGI). The rationale for intensive investigation of Arabidopsis is that it is an excellent model for higher plants. In order to maximize use of the knowledge gained about this plant, there is a need for a comprehensive database and information retrieval and analysis system that will provide user-friendly access to Arabidopsis information. This paper describes the initial steps we have taken toward realizing these goals in a project called The Arabidopsis Information Resource (TAIR) (www.arabidopsis.org).     

The protein identification resource (PIR)

The Protein Identification Resource consists of an integrated computer system composed of a number of protein and nucleic acid sequence databases and software designed for the identification and analysis of protein sequences and their corresponding coding sequences. The PIR serves the scientific community through on-line access, distributing magnetic tapes, and performing off-line sequence identification services for researchers.     

Published and Perished? The Influence of the Searched Protein Database on the Long-Term Storage of Proteomics Data

In proteomics, protein identifications are reported and stored using an unstable reference system: protein identifiers. These proprietary identifiers are created individually by every protein database and can change or may even be deleted over time. To estimate the effect of the searched protein sequence database on the long-term storage of proteomics data we analyzed the changes of reported protein identifiers from all public experiments in the Proteomics Identifications (PRIDE) database by November 2010. To map the submitted protein identifier to a currently active entry, two distinct approaches were used. The first approach used the Protein Identifier Cross Referencing (PICR) service at the EBI, which maps protein identifiers based on 100% sequence identity. The second one (called logical mapping algorithm) accessed the source databases and retrieved the current status of the reported identifier. Our analysis showed the differences between the main protein databases (International Protein Index (IPI), UniProt Knowledgebase (UniProtKB), National Center for Biotechnological Information nr database (NCBI nr), and Ensembl) in respect to identifier stability. For example, whereas 20% of submitted IPI entries were deleted after two years, virtually all UniProtKB entries remained either active or replaced. Furthermore, the two mapping algorithms produced markedly different results. For example, the PICR service reported 10% more IPI entries deleted compared with the logical mapping algorithm. We found several cases where experiments contained more than 10% deleted identifiers already at the time of publication. We also assessed the proportion of peptide identifications in these data sets that still fitted the originally identified protein sequences. Finally, we performed the same overall analysis on all records from IPI, Ensembl, and UniProtKB: two releases per year were used, from 2005. This analysis showed for the first time the true effect of changing protein identifiers on proteomics data. Based on these findings, UniProtKB seems the best database for applications that rely on the long-term storage of proteomics data.     

The EBI SRS server-new features

MOTIVATION: Here we report on recent developments at the EBI SRS server (http://srs.ebi.ac.uk). SRS has become an integration system for both data retrieval and sequence analysis applications. The EBI SRS server is a primary gateway to major databases in the field of molecular biology produced and supported at EBI as well as European public access point to the MEDLINE database provided by US National Library of Medicine (NLM). It is a reference server for latest developments in data and application integration. The new additions include: concept of virtual databases, integration of XML databases like the Integrated Resource of Protein Domains and Functional Sites (InterPro), Gene Ontology (GO), MEDLINE, Metabolic pathways, etc., user friendly data representation in 'Nice views', SRSQuickSearch bookmarklets. AVAILABILITY: SRS6 is a licensed product of LION Bioscience AG freely available for academics. The EBI SRS server (http://srs.ebi.ac.uk) is a free central resource for molecular biology data as well as a reference server for the latest developments in data integration.     

The Protein Information Resource

The Protein Information Resource (PIR) is an integrated public resource of protein informatics that supports genomic and proteomic research and scientific discovery. PIR maintains the Protein Sequence Database (PSD), an annotated protein database containing over 283 000 sequences covering the entire taxonomic range. Family classification is used for sensitive identification, consistent annotation, and detection of annotation errors. The superfamily curation defines signature domain architecture and categorizes memberships to improve automated classification. To increase the amount of experimental annotation, the PIR has developed a bibliography system for literature searching, mapping, and user submission, and has conducted retrospective attribution of citations for experimental features. PIR also maintains NREF, a non-redundant reference database, and iProClass, an integrated database of protein family, function, and structure information. PIR-NREF provides a timely and comprehensive collection of protein sequences, currently consisting of more than 1 000 000 entries from PIR-PSD, SWISS-PROT, TrEMBL, RefSeq, GenPept, and PDB. The PIR web site (http://pir.georgetown.edu) connects data analysis tools to underlying databases for information retrieval and knowledge discovery, with functionalities for interactive queries, combinations of sequence and text searches, and sorting and visual exploration of search results. The FTP site provides free download for PSD and NREF biweekly releases and auxiliary databases and files.     

Towards Interoperability in Genome Databases: The MAtDB (MIPS Arabidopsis Thaliana Database) Experience

Increasing numbers of whole-genome sequences are available, but to interpret them fully requires more than listing all genes. Genome databases are faced with the challenges of integrating heterogenous data and enabling data mining. In comparison to a data warehousing approach, where integration is achieved through replication of all relevant data in a unified schema, distributed approaches provide greater flexibility and maintainability. These are important in a field where new data is generated rapidly and our understanding of the data changes. Interoperability between distributed data sources allows data maintenance to be separated from integration and analysis. Simple ways to access the data can facilitate the development of new data mining tools and the transition from model genome analysis to comparative genomics. With the MIPS Arabidopsis thaliana genome database (MAtDB, http://mips.gsf.de/proj/thal/db) our aim is to go beyond a data repository towards creating an integrated knowledge resource. To this end, the Arabidopsis genome has been a backbone against which to structure and integrate heterogenous data. The challenges to be met are continuous updating of data, the design of flexible data models that can evolve with new data, the integration of heterogenous data, e.g. through the use of ontologies, comprehensive views and visualization of complex information, simple interfaces for application access locally or via the Internet, and knowledge transfer across species.     

PIR: a new resource for bioinformatics

SUMMARY: The Protein Information Resource (PIR) has greatly expanded its Web site and developed a set of interactive search and analysis tools to facilitate the analysis, annotation, and functional identification of proteins. New search engines have been implemented to combine sequence similarity search results with database annotation information. The new PIR search systems have proved very useful in providing enriched functional annotation of protein sequences, determining protein superfamily-domain relationships, and detecting annotation errors in genomic database archives. AVAILABILITY: http://pir.georgetown.edu/. CONTACT: mcgarvey@nbrf.georgetown.edu     

KAREBrowser: SNP database of Korea Association REsource Project

The International HapMap Project and the Human Genome Diversity Project (HGDP) provide plentiful resources on human genome information to the public. However, this kind of information is limited because of the small sample size in both databases. A Genome-Wide Association Study has been conducted with 8,842 Korean subjects as a part of the Korea Association Resource (KARE) project. In an effort to build a publicly available browsing system for genome data resulted from large scale KARE GWAS, we developed the KARE browser. This browser provides users with a large amount of single nucleotide polymorphisms (SNPs) information comprising 1.5 million SNPs from population-based cohorts of 8,842 samples. KAREBrowser was based on the generic genome browser (GBrowse), a webbased application tool developed for users to navigate and visualize the genomic features and annotations in an interactive manner. All SNP information and related functions are available at the web site http://ksnp.cdc. go.kr/karebrowser/.