RESUMEN
CORUM is a database that provides a manually curated repository of experimentally characterized protein complexes from mammalian organisms, mainly human (67%), mouse (15%) and rat (10%). Given the vital functions of these macromolecular machines, their identification and functional characterization is foundational to our understanding of normal and disease biology. The new CORUM 3.0 release encompasses 4274 protein complexes offering the largest and most comprehensive publicly available dataset of mammalian protein complexes. The CORUM dataset is built from 4473 different genes, representing 22% of the protein coding genes in humans. Protein complexes are described by a protein complex name, subunit composition, cellular functions as well as the literature references. Information about stoichiometry of subunits depends on availability of experimental data. Recent developments include a graphical tool displaying known interactions between subunits. This allows the prediction of structural interconnections within protein complexes of unknown structure. In addition, we present a set of 58 protein complexes with alternatively spliced subunits. Those were found to affect cellular functions such as regulation of apoptotic activity, protein complex assembly or define cellular localization. CORUM is freely accessible at http://mips.helmholtz-muenchen.de/corum/.
Asunto(s)
Bases de Datos de Proteínas , Complejos Multiproteicos/química , Complejos Multiproteicos/metabolismo , Empalme Alternativo , Animales , Humanos , Ratones , Complejos Multiproteicos/genética , Conformación Proteica , Mapeo de Interacción de Proteínas , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , RatasRESUMEN
OBJECTIVE: The comprehensive assaying of low-molecular-weight compounds, for example, metabolomics, provides a unique tool to uncover novel biomarkers and understand pathways underlying myocardial infarction (MI). We used a targeted metabolomics approach to identify biomarkers for MI and evaluate their involvement in the pathogenesis of MI. METHODS AND RESULTS: Using three independent, prospective cohorts (KORA S4, KORA S2 and AGES-REFINE), totalling 2257 participants without a history of MI at baseline, we identified metabolites associated with incident MI (266 cases). We also investigated the association between the metabolites and high-sensitivity C reactive protein (hsCRP) to understand the relation between these metabolites and systemic inflammation. Out of 140 metabolites, 16 were nominally associated (p<0.05) with incident MI in KORA S4. Three metabolites, arginine and two lysophosphatidylcholines (LPC 17:0 and LPC 18:2), were selected as biomarkers via a backward stepwise selection procedure in the KORA S4 and were significant (p<0.0003) in a meta-analysis comprising all three studies including KORA S2 and AGES-REFINE. Furthermore, these three metabolites increased the predictive value of the Framingham risk score, increasing the area under the receiver operating characteristic score in KORA S4 (from 0.70 to 0.78, p=0.001) and AGES-REFINE study (from 0.70 to 0.76, p=0.02), but was not observed in KORA S2. The metabolite biomarkers attenuated the association between hsCRP and MI, indicating a potential link to systemic inflammatory processes. CONCLUSIONS: We identified three metabolite biomarkers, which in combination increase the predictive value of the Framingham risk score. The attenuation of the hsCRP-MI association by these three metabolites indicates a potential link to systemic inflammation.
Asunto(s)
Biomarcadores/metabolismo , Inflamación/metabolismo , Infarto del Miocardio/metabolismo , Medición de Riesgo/métodos , Adulto , Anciano , Progresión de la Enfermedad , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
CORUM is a database that provides a manually curated repository of experimentally characterized protein complexes from mammalian organisms, mainly human (64%), mouse (16%) and rat (12%). Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. The new CORUM 2.0 release encompasses 2837 protein complexes offering the largest and most comprehensive publicly available dataset of mammalian protein complexes. The CORUM dataset is built from 3198 different genes, representing approximately 16% of the protein coding genes in humans. Each protein complex is described by a protein complex name, subunit composition, function as well as the literature reference that characterizes the respective protein complex. Recent developments include mapping of functional annotation to Gene Ontology terms as well as cross-references to Entrez Gene identifiers. In addition, a 'Phylogenetic Conservation' analysis tool was implemented that analyses the potential occurrence of orthologous protein complex subunits in mammals and other selected groups of organisms. This allows one to predict the occurrence of protein complexes in different phylogenetic groups. CORUM is freely accessible at (http://mips.helmholtz-muenchen.de/genre/proj/corum/index.html).
Asunto(s)
Biología Computacional/métodos , Bases de Datos Genéticas , Bases de Datos de Proteínas , Complejos Multiproteicos , Animales , Biología Computacional/tendencias , Humanos , Almacenamiento y Recuperación de la Información/métodos , Internet , Ratones , Filogenia , Estructura Terciaria de Proteína , Ratas , Saccharomyces cerevisiae/genética , Programas InformáticosRESUMEN
UNLABELLED: Cross-mapping of gene and protein identifiers between different databases is a tedious and time-consuming task. To overcome this, we developed CRONOS, a cross-reference server that contains entries from five mammalian organisms presented by major gene and protein information resources. Sequence similarity analysis of the mapped entries shows that the cross-references are highly accurate. In total, up to 18 different identifier types can be used for identification of cross-references. The quality of the mapping could be improved substantially by exclusion of ambiguous gene and protein names which were manually validated. Organism-specific lists of ambiguous terms, which are valuable for a variety of bioinformatics applications like text mining are available for download. AVAILABILITY: CRONOS is freely available to non-commercial users at http://mips.gsf.de/genre/proj/cronos/index.html, web services are available at http://mips.gsf.de/CronosWSService/CronosWS?wsdl.
Asunto(s)
Biología Computacional/instrumentación , Biología Computacional/métodos , Internet , Programas Informáticos , Animales , Genes , Humanos , ProteínasRESUMEN
Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. The CORUM (http://mips.gsf.de/genre/proj/corum/index.html) database is a collection of experimentally verified mammalian protein complexes. Information is manually derived by critical reading of the scientific literature from expert annotators. Information about protein complexes includes protein complex names, subunits, literature references as well as the function of the complexes. For functional annotation, we use the FunCat catalogue that enables to organize the protein complex space into biologically meaningful subsets. The database contains more than 1750 protein complexes that are built from 2400 different genes, thus representing 12% of the protein-coding genes in human. A web-based system is available to query, view and download the data. CORUM provides a comprehensive dataset of protein complexes for discoveries in systems biology, analyses of protein networks and protein complex-associated diseases. Comparable to the MIPS reference dataset of protein complexes from yeast, CORUM intends to serve as a reference for mammalian protein complexes.
Asunto(s)
Bases de Datos de Proteínas , Complejos Multiproteicos/fisiología , Animales , Humanos , Internet , Ratones , Complejos Multiproteicos/análisis , Complejos Multiproteicos/química , Ratas , Interfaz Usuario-ComputadorRESUMEN
MfunGD (http://mips.gsf.de/genre/proj/mfungd/) provides a resource for annotated mouse proteins and their occurrence in protein networks. Manual annotation concentrates on proteins which are found to interact physically with other proteins. Accordingly, manually curated information from a protein-protein interaction database (MPPI) and a database of mammalian protein complexes is interconnected with MfunGD. Protein function annotation is performed using the Functional Catalogue (FunCat) annotation scheme which is widely used for the analysis of protein networks. The dataset is also supplemented with information about the literature that was used in the annotation process as well as links to the SIMAP Fasta database, the Pedant protein analysis system and cross-references to external resources. Proteins that so far were not manually inspected are annotated automatically by a graphical probabilistic model and/or superparamagnetic clustering. The database is continuously expanding to include the rapidly growing amount of functional information about gene products from mouse. MfunGD is implemented in GenRE, a J2EE-based component-oriented multi-tier architecture following the separation of concern principle.
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Bases de Datos Genéticas , Genómica , Ratones/genética , Complejos Multiproteicos/genética , Complejos Multiproteicos/fisiología , Animales , Internet , Complejos Multiproteicos/química , Proteómica , Programas Informáticos , Interfaz Usuario-ComputadorRESUMEN
MOTIVATION: Any development of new methods for automatic functional annotation of proteins according to their sequences requires high-quality data (as benchmark) as well as tedious preparatory work to generate sequence parameters required as input data for the machine learning methods. Different program settings and incompatible protocols make a comparison of the analyzed methods difficult. RESULTS: The MIPS Bacterial Functional Annotation Benchmark dataset (MIPS-BFAB) is a new, high-quality resource comprising four bacterial genomes manually annotated according to the MIPS functional catalogue (FunCat). These resources include precalculated sequence parameters, such as sequence similarity scores, InterPro domain composition and other parameters that could be used to develop and benchmark methods for functional annotation of bacterial protein sequences. These data are provided in XML format and can be used by scientists who are not necessarily experts in genome annotation. AVAILABILITY: BFAB is available at http://mips.gsf.de/proj/bfab
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Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Benchmarking/métodos , Mapeo Cromosómico/métodos , Sistemas de Administración de Bases de Datos , Bases de Datos de Proteínas , Documentación/métodos , Genoma Bacteriano , Proteínas Bacterianas/clasificación , Almacenamiento y Recuperación de la Información/métodos , InternetRESUMEN
SUMMARY: The MIPS mammalian protein-protein interaction database (MPPI) is a new resource of high-quality experimental protein interaction data in mammals. The content is based on published experimental evidence that has been processed by human expert curators. We provide the full dataset for download and a flexible and powerful web interface for users with various requirements.