204 research outputs found

    EcID. A database for the inference of functional interactions in E. coli

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    The EcID database (Escherichia coli Interaction Database) provides a framework for the integration of information on functional interactions extracted from the following sources: EcoCyc (metabolic pathways, protein complexes and regulatory information), KEGG (metabolic pathways), MINT and IntAct (protein interactions). It also includes information on protein complexes from the two E. coli high-throughput pull-down experiments and potential interactions extracted from the literature using the web services associated to the iHOP text-mining system. Additionally, EcID incorporates results of various prediction methods, including two protein interaction prediction methods based on genomic information (Phylogenetic Profiles and Gene Neighbourhoods) and three methods based on the analysis of co-evolution (Mirror Tree, In Silico 2 Hybrid and Context Mirror). EcID associates to each prediction a specifically developed confidence score. The two main features that make EcID different from other systems are the combination of co-evolution-based predictions with the experimental data, and the introduction of E. coli-specific information, such as gene regulation information from EcoCyc. The possibilities offered by the combination of the EcID database information are illustrated with a prediction of potential functions for a group of poorly characterized genes related to yeaG. EcID is available online at http://ecid.bioinfo.cnio.es

    EcID. A database for the inference of functional interactions in E. coli

    Get PDF
    The EcID database (Escherichia coli Interaction Database) provides a framework for the integration of information on functional interactions extracted from the following sources: EcoCyc (metabolic pathways, protein complexes and regulatory information), KEGG (metabolic pathways), MINT and IntAct (protein interactions). It also includes information on protein complexes from the two E. coli high-throughput pull-down experiments and potential interactions extracted from the literature using the web services associated to the iHOP text-mining system. Additionally, EcID incorporates results of various prediction methods, including two protein interaction prediction methods based on genomic information (Phylogenetic Profiles and Gene Neighbourhoods) and three methods based on the analysis of co-evolution (Mirror Tree, In Silico 2 Hybrid and Context Mirror). EcID associates to each prediction a specifically developed confidence score. The two main features that make EcID different from other systems are the combination of co-evolution-based predictions with the experimental data, and the introduction of E. coli-specific information, such as gene regulation information from EcoCyc. The possibilities offered by the combination of the EcID database information are illustrated with a prediction of potential functions for a group of poorly characterized genes related to yeaG. EcID is available online at http://ecid.bioinfo.cnio.es

    A proteogenomic update to Yersinia: enhancing genome annotation

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    <p>Abstract</p> <p>Background</p> <p>Modern biomedical research depends on a complete and accurate proteome. With the widespread adoption of new sequencing technologies, genome sequences are generated at a near exponential rate, diminishing the time and effort that can be invested in genome annotation. The resulting gene set contains numerous errors in even the most basic form of annotation: the primary structure of the proteins.</p> <p>Results</p> <p>The application of experimental proteomics data to genome annotation, called proteogenomics, can quickly and efficiently discover misannotations, yielding a more accurate and complete genome annotation. We present a comprehensive proteogenomic analysis of the plague bacterium, <it>Yersinia pestis KIM</it>. We discover non-annotated genes, correct protein boundaries, remove spuriously annotated ORFs, and make major advances towards accurate identification of signal peptides. Finally, we apply our data to 21 other <it>Yersinia </it>genomes, correcting and enhancing their annotations.</p> <p>Conclusions</p> <p>In total, 141 gene models were altered and have been updated in RefSeq and Genbank, which can be accessed seamlessly through any NCBI tool (e.g. blast) or downloaded directly. Along with the improved gene models we discover new, more accurate means of identifying signal peptides in proteomics data.</p

    Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set Analyses

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    PURPOSE: Recent studies indicate that mitochondrial proteins may contribute to the pathogenesis of primary open-angle glaucoma (POAG). In this study, we examined the association between POAG and common variations in gene-encoding mitochondrial proteins. METHODS: We examined genetic data from 3430 POAG cases and 3108 controls derived from the combination of the GLAUGEN and NEIGHBOR studies. We constructed biological-system coherent mitochondrial nuclear-encoded protein gene-sets by intersecting the MitoCarta database with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We examined the mitochondrial gene-sets for association with POAG and with normal-tension glaucoma (NTG) and high-tension glaucoma (HTG) subsets using Pathway Analysis by Randomization Incorporating Structure. RESULTS: We identified 22 KEGG pathways with significant mitochondrial protein-encoding gene enrichment, belonging to six general biological classes. Among the pathway classes, mitochondrial lipid metabolism was associated with POAG overall (P = 0.013) and with NTG (P = 0.0006), and mitochondrial carbohydrate metabolism was associated with NTG (P = 0.030). Examining the individual KEGG pathway mitochondrial gene-sets, fatty acid elongation and synthesis and degradation of ketone bodies, both lipid metabolism pathways, were significantly associated with POAG (P = 0.005 and P = 0.002, respectively) and NTG (P = 0.0004 and P < 0.0001, respectively). Butanoate metabolism, a carbohydrate metabolism pathway, was significantly associated with POAG (P = 0.004), NTG (P = 0.001), and HTG (P = 0.010). CONCLUSIONS: We present an effective approach for assessing the contributions of mitochondrial genetic variation to open-angle glaucoma. Our findings support a role for mitochondria in POAG pathogenesis and specifically point to lipid and carbohydrate metabolism pathways as being important

    Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility

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    Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with kno

    Author Correction: Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

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    Emmanuelle Souzeau, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this Article. This has now been corrected in both the PDF and HTML versions of the Article

    Consensus recommendations on organization of care for individuals with Phelan-McDermid syndrome

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    The manifestations of Phelan-McDermid syndrome (PMS) are complex, warranting expert and multidisciplinary care in all life stages. In the present paper we propose consensus recommendations on the organization of care for individuals with PMS. We indicate that care should consider all life domains, which can be done within the framework of the International Classification of Functioning, Disability and Health (ICF). This framework assesses disability and functioning as the outcome of the individual's interactions with other factors. The different roles within care, such as performed by a centre of expertise, by regional health care providers and by a coordinating physician are addressed. A surveillance scheme and emergency card is provided and disciplines participating in a multidisciplinary team for PMS are described. Additionally, recommendations are provided for transition from paediatric to adult care. This care proposition may also be useful for individuals with other rare genetic neurodevelopmental disorders.</p
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