SORGOdb: Superoxide Reductase Gene Ontology curated DataBase

<p>Abstract</p> <p>Background</p> <p>Superoxide reductases (SOR) catalyse the reduction of superoxide anions to hydrogen peroxide and are involved in the oxidative stress defences of anaerobic and facultative anaerobic organisms. Genes encoding SOR were discovered recently and suffer from annotation problems. These genes, named <it>sor</it>, are short and the transfer of annotations from previously characterized neelaredoxin, desulfoferrodoxin, superoxide reductase and rubredoxin oxidase has been heterogeneous. Consequently, many <it>sor </it>remain anonymous or mis-annotated.</p> <p>Description</p> <p>SORGOdb is an exhaustive database of SOR that proposes a new classification based on domain architecture. SORGOdb supplies a simple user-friendly web-based database for retrieving and exploring relevant information about the proposed SOR families. The database can be queried using an organism name, a locus tag or phylogenetic criteria, and also offers sequence similarity searches using BlastP. Genes encoding SOR have been re-annotated in all available genome sequences (prokaryotic and eukaryotic (complete and in draft) genomes, updated in May 2010).</p> <p>Conclusions</p> <p>SORGOdb contains 325 non-redundant and curated SOR, from 274 organisms. It proposes a new classification of SOR into seven different classes and allows biologists to explore and analyze <it>sor </it>in order to establish correlations between the class of SOR and organism phenotypes. SORGOdb is freely available at <url>http://sorgo.genouest.org/index.php</url>.</p

CoBaltDB: Complete bacterial and archaeal orfeomes subcellular localization database and associated resources

International audienceBACKGROUND: The functions of proteins are strongly related to their localization in cell compartments (for example the cytoplasm or membranes) but the experimental determination of the sub-cellular localization of proteomes is laborious and expensive. A fast and low-cost alternative approach is in silico prediction, based on features of the protein primary sequences. However, biologists are confronted with a very large number of computational tools that use different methods that address various localization features with diverse specificities and sensitivities. As a result, exploiting these computer resources to predict protein localization accurately involves querying all tools and comparing every prediction output; this is a painstaking task. Therefore, we developed a comprehensive database, called CoBaltDB, that gathers all prediction outputs concerning complete prokaryotic proteomes. DESCRIPTION: The current version of CoBaltDB integrates the results of 43 localization predictors for 784 complete bacterial and archaeal proteomes (2.548.292 proteins in total). CoBaltDB supplies a simple user-friendly interface for retrieving and exploring relevant information about predicted features (such as signal peptide cleavage sites and transmembrane segments). Data are organized into three work-sets ("specialized tools", "meta-tools" and "additional tools"). The database can be queried using the organism name, a locus tag or a list of locus tags and may be browsed using numerous graphical and text displays. CONCLUSIONS: With its new functionalities, CoBaltDB is a novel powerful platform that provides easy access to the results of multiple localization tools and support for predicting prokaryotic protein localizations with higher confidence than previously possible. CoBaltDB is available at http://www.umr6026.univ-rennes1.fr/english/home/research/basic/software/cobalten

Statistical and probabilistic modeling of a cloud of particles coupled with a turbulent fluid

This paper exposes a novel exploratory formalism, the end goal of which is the numerical simulation of the dynamics of a cloud of particles weakly or strongly coupled with a turbulent fluid. Given the large panel of expertise of the list of authors, the content of this paper scans a wide range of connex notions, from the physics of turbulence to the rigorous definition of stochastic processes. Our approach is to develop reduced-order models for the dynamics of both carrying and carried phases which remain consistant within this formalism, and to set up a numerical process to validate these models. The novelties of this paper lie in the gathering of a large panel of mathematical and physical definitions and results within a common framework and an agreed vocabulary (sections 1 and 2), and in some preliminary results and achievements within this context, section 3. While the first three sections have been simplified to the context of a gas field providing that the disperse phase only retrieves energy through drag, the fourth section opens this study to the more complex situation when the disperse phase interacts with the continuous phase as well, in an energy conservative manner. This will allow us to expose the perspectives of the project and to conclude

Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy.

OBJECTIVE: To improve the genetic diagnosis of dominant optic atrophy (DOA), the most frequently inherited optic nerve disease, and infer genotype-phenotype correlations. METHODS: Exonic sequences of 22 genes were screened by new-generation sequencing in patients with DOA who were investigated for ophthalmology, neurology, and brain MRI. RESULTS: We identified 7 and 8 new heterozygous pathogenic variants in SPG7 and AFG3L2. Both genes encode for mitochondrial matricial AAA (m-AAA) proteases, initially involved in recessive hereditary spastic paraplegia type 7 (HSP7) and dominant spinocerebellar ataxia 28 (SCA28), respectively. Notably, variants in AFG3L2 that result in DOA are located in different domains to those reported in SCA28, which likely explains the lack of clinical overlap between these 2 phenotypic manifestations. In comparison, the SPG7 variants identified in DOA are interspersed among those responsible for HSP7 in which optic neuropathy has previously been reported. CONCLUSIONS: Our results position SPG7 and AFG3L2 as candidate genes to be screened in DOA and indicate that regulation of mitochondrial protein homeostasis and maturation by m-AAA proteases are crucial for the maintenance of optic nerve physiology

Dominant ACO2 mutations are a frequent cause of isolated optic atrophy.

Biallelic mutations in ACO2, encoding the mitochondrial aconitase 2, have been identified in individuals with neurodegenerative syndromes, including infantile cerebellar retinal degeneration and recessive optic neuropathies (locus OPA9). By screening European cohorts of individuals with genetically unsolved inherited optic neuropathies, we identified 61 cases harbouring variants in ACO2, among whom 50 carried dominant mutations, emphasizing for the first time the important contribution of ACO2 monoallelic pathogenic variants to dominant optic atrophy. Analysis of the ophthalmological and clinical data revealed that recessive cases are affected more severely than dominant cases, while not significantly earlier. In addition, 27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy. In silico analyses of ACO2 variants predicted their deleterious impacts on ACO2 biophysical properties. Skin derived fibroblasts from patients harbouring dominant and recessive ACO2 mutations revealed a reduction of ACO2 abundance and enzymatic activity, and the impairment of the mitochondrial respiration using citrate and pyruvate as substrates, while the addition of other Krebs cycle intermediates restored a normal respiration, suggesting a possible short-cut adaptation of the tricarboxylic citric acid cycle. Analysis of the mitochondrial genome abundance disclosed a significant reduction of the mitochondrial DNA amount in all ACO2 fibroblasts. Overall, our data position ACO2 as the third most frequently mutated gene in autosomal inherited optic neuropathies, after OPA1 and WFS1, and emphasize the crucial involvement of the first steps of the Krebs cycle in the maintenance and survival of retinal ganglion cells

CoBalt : Consensus-Based Localization Tool.

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A snapshot of some pLI score pitfalls

International audienceThe pLI score reflects the tolerance of a given gene to the loss of function on the basis of the number of protein truncating variants, that is, the frameshift, splice donor, splice acceptor, and stop-gain variants referenced for this gene in control databases weighted by the size of the gene and the sequencing coverage. It is frequently used to prioritize candidate genes when analyzing whole exome or whole genome data. We list here the main pitfalls to consider before using this score. Concrete illustrations are given for each of these pitfalls.</p

OxyGene&Co : Combining CoBalt and OxyGene to improve the functional annotation of oxidative stress subsystems.

Poste

High- throughput sequencing revealed a novel SETX mutation in a Hungarian patient with amyotrophic lateral sclerosis

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of the motor neurons. To date, 126 genes have been implicated in ALS. Therefore, the heterogenous genetic background of ALS requires comprehensive genetic investigative approaches. METHODS: In this study, DNA from 28 Hungarian ALS patients was subjected to targeted high-throughput sequencing of the coding regions of three Mendelian ALS genes: , and . RESULTS: A novel heterozygous missense mutation (c.791A&gt;G, p.N264S) of the gene was identified in a female patient presenting an atypical ALS phenotype, including adult onset and lower motor neuron impairment. No further mutations were detected in the other Mendelian ALS genes investigated. CONCLUSION: Our study contributes to the understanding of the genetic and phenotypic diversity of motor neuron diseases (MNDs). Our results also suggest that the elucidation of the genetic background of MNDs requires a complex approach, including the screening of both Mendelian and non-Mendelian genes

Statistical and probabilistic modeling of a cloud of particles coupled with a turbulent fluid

International audienceThis paper exposes a novel exploratory formalism, which end goal is the numerical simulation of the dynamics of a cloud of particles weakly or strongly coupled with a turbulent fluid. Giventhe large panel of expertise of the list of authors, the content of this paper scans a wide range of connexnotions, from the physics of turbulence to the rigorous definition of stochastic processes. Our approachis to develop reduced-order models for the dynamics of both carrying and carried phases which remainconsistant within this formalism, and to set up a numerical process to validate these models. Thenovelties of this paper lie in the gathering of a large panel of mathematical and physical definitionsand results within a common framework and an agreed vocabulary (sections 1 and 2), and in somepreliminary results and achievements within this context, section 3. While the first three sections havebeen simplified to the context of a gas field providing that the disperse phase only retrieves energythrough drag, the fourth section opens this study to the more complex situation when the dispersephase interacts with the continuous phase as well, in an energy conservative manner. This will allowus to expose the perspectives of the project and to conclude