RESUMEN
We present the first analysis of the human proteome with regard to interactions between proteins. We also compare the human interactome with the available interaction datasets from yeast (Saccharomyces cerevisiae), worm (Caenorhabditis elegans) and fly (Drosophila melanogaster). Of >70,000 binary interactions, only 42 were common to human, worm and fly, and only 16 were common to all four datasets. An additional 36 interactions were common to fly and worm but were not observed in humans, although a coimmunoprecipitation assay showed that 9 of the interactions do occur in humans. A re-examination of the connectivity of essential genes in yeast and humans indicated that the available data do not support the presumption that the number of interaction partners can accurately predict whether a gene is essential. Finally, we found that proteins encoded by genes mutated in inherited genetic disorders are likely to interact with proteins known to cause similar disorders, suggesting the existence of disease subnetworks. The human interaction map constructed from our analysis should facilitate an integrative systems biology approach to elucidating the cellular networks that contribute to health and disease states.
Asunto(s)
Proteínas de Caenorhabditis elegans/genética , Proteínas de Drosophila/genética , Proteoma/genética , Proteínas de Saccharomyces cerevisiae/genética , Animales , Caenorhabditis elegans/genética , Dípteros , Drosophila melanogaster , Evolución Molecular , HumanosAsunto(s)
Cromosomas Humanos X/genética , Empalme Alternativo , Secuencia de Aminoácidos , Secuencia de Bases , Mapeo Cromosómico , Biología Computacional , ADN Complementario/genética , Bases de Datos Genéticas , Bases de Datos de Proteínas , Exones , Humanos , Datos de Secuencia Molecular , Sistemas de Lectura Abierta/fisiología , Alineación de SecuenciaRESUMEN
Human Protein Reference Database (HPRD) (http://www.hprd.org) was developed to serve as a comprehensive collection of protein features, post-translational modifications (PTMs) and protein-protein interactions. Since the original report, this database has increased to >20 000 proteins entries and has become the largest database for literature-derived protein-protein interactions (>30 000) and PTMs (>8000) for human proteins. We have also introduced several new features in HPRD including: (i) protein isoforms, (ii) enhanced search options, (iii) linking of pathway annotations and (iv) integration of a novel browser, GenProt Viewer (http://www.genprot.org), developed by us that allows integration of genomic and proteomic information. With the continued support and active participation by the biomedical community, we expect HPRD to become a unique source of curated information for the human proteome and spur biomedical discoveries based on integration of genomic, transcriptomic and proteomic data.
Asunto(s)
Bases de Datos de Proteínas , Proteoma/genética , Proteoma/fisiología , Bases de Datos de Proteínas/estadística & datos numéricos , Genómica , Humanos , Internet , Mapeo de Interacción de Proteínas , Isoformas de Proteínas/análisis , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiología , Procesamiento Proteico-Postraduccional , Proteínas/análisis , Proteínas/genética , Proteínas/fisiología , Proteoma/química , Proteómica , Transducción de Señal , Integración de Sistemas , Interfaz Usuario-ComputadorRESUMEN
The rapid pace at which genomic and proteomic data is being generated necessitates the development of tools and resources for managing data that allow integration of information from disparate sources. The Human Protein Reference Database (http://www.hprd.org) is a web-based resource based on open source technologies for protein information about several aspects of human proteins including protein-protein interactions, post-translational modifications, enzyme-substrate relationships and disease associations. This information was derived manually by a critical reading of the published literature by expert biologists and through bioinformatics analyses of the protein sequence. This database will assist in biomedical discoveries by serving as a resource of genomic and proteomic information and providing an integrated view of sequence, structure, function and protein networks in health and disease.
Asunto(s)
Bases de Datos de Proteínas , Proteínas/metabolismo , Proteómica , Biología Computacional , Enfermedad , Genómica , Humanos , Almacenamiento y Recuperación de la Información , Internet , Unión Proteica , Procesamiento Proteico-Postraduccional , Proteínas/química , Proteínas/genética , Proteoma/química , Proteoma/genética , Proteoma/metabolismo , Especificidad por Sustrato , Vocabulario ControladoRESUMEN
Plasma is one of the best studied compartments in the human body and serves as an ideal body fluid for the diagnosis of diseases. This report provides a detailed functional annotation of all the plasma proteins identified to date. In all, gene products encoded by 3778 distinct genes were annotated based on proteins previously published in the literature as plasma proteins and the identification of multiple peptides from proteins under HUPO's Plasma Proteome Project. Our analysis revealed that 51% of these genes encoded more than one protein isoform. All single nucleotide polymorphisms involving protein-coding regions were mapped onto the protein sequences. We found a number of examples of isoform-specific subcellular localization as well as tissue expression. This database is an attempt at comprehensive annotation of a complex subproteome and is available on the web at http://www.plasmaproteomedatabase.org.
Asunto(s)
Proteínas Sanguíneas/química , Proteínas Sanguíneas/genética , Bases de Datos de Proteínas , Proteómica/métodos , Secuencias de Aminoácidos , Biología Computacional/métodos , Genoma Humano , Humanos , Espectrometría de Masas , Péptidos/química , Polimorfismo de Nucleótido Simple , Isoformas de Proteínas , Estructura Terciaria de Proteína , Factores de TiempoRESUMEN
Human Protein Reference Database (HPRD) is an object database that integrates a wealth of information relevant to the function of human proteins in health and disease. Data pertaining to thousands of protein-protein interactions, posttranslational modifications, enzyme/substrate relationships, disease associations, tissue expression, and subcellular localization were extracted from the literature for a nonredundant set of 2750 human proteins. Almost all the information was obtained manually by biologists who read and interpreted >300,000 published articles during the annotation process. This database, which has an intuitive query interface allowing easy access to all the features of proteins, was built by using open source technologies and will be freely available at http://www.hprd.org to the academic community. This unified bioinformatics platform will be useful in cataloging and mining the large number of proteomic interactions and alterations that will be discovered in the postgenomic era.