Broadening the horizon--level 2.5 of the HUPO-PSI format for molecular interactions.

BACKGROUND: Molecular interaction Information is a key resource in modern biomedical research. Publicly available data have previously been provided in a broad array of diverse formats, making access to this very difficult. The publication and wide implementation of the Human Proteome Organisation Proteomics Standards Initiative Molecular Interactions (HUPO PSI-MI) format in 2004 was a major step towards the establishment of a single, unified format by which molecular interactions should be presented, but focused purely on protein-protein interactions. RESULTS: The HUPO-PSI has further developed the PSI-MI XML schema to enable the description of interactions between a wider range of molecular types, for example nucleic acids, chemical entities, and molecular complexes. Extensive details about each supported molecular interaction can now be captured, including the biological role of each molecule within that interaction, detailed description of interacting domains, and the kinetic parameters of the interaction. The format is supported by data management and analysis tools and has been adopted by major interaction data providers. Additionally, a simpler, tab-delimited format MITAB2.5 has been developed for the benefit of users who require only minimal information in an easy to access configuration. CONCLUSION: The PSI-MI XML2.5 and MITAB2.5 formats have been jointly developed by interaction data producers and providers from both the academic and commercial sector, and are already widely implemented and well supported by an active development community. PSI-MI XML2.5 enables the description of highly detailed molecular interaction data and facilitates data exchange between databases and users without loss of information. MITAB2.5 is a simpler format appropriate for fast Perl parsing or loading into Microsoft Excel.

Individual patient data systematic review and meta-analysis of optic nerve sheath diameter ultrasonography for detecting raised intracranial pressure: protocol of the ONSD research group.

BACKGROUND: The purpose of the optic nerve sheath diameter (ONSD) research group project is to establish an individual patient-level database from high quality studies of ONSD ultrasonography for the detection of raised intracranial pressure (ICP), and to perform a systematic review and an individual patient data meta-analysis (IPDMA), which will provide a cutoff value to help physicians making decisions and encourage further research. Previous meta-analyses were able to assess the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP but failed to determine a precise cutoff value. Thus, the ONSD research group was founded to synthesize data from several recent studies on the subject and to provide evidence on the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP. METHODS: This IPDMA will be conducted in different phases. First, we will systematically search for eligible studies. To be eligible, studies must have compared ONSD ultrasonography to invasive intracranial devices, the current reference standard for diagnosing raised ICP. Subsequently, we will assess the quality of studies included based on the QUADAS-2 tool, and then collect and validate individual patient data. The objectives of the primary analyses will be to assess the diagnostic accuracy of ONSD ultrasonography and to determine a precise cutoff value for detecting raised ICP. Secondly, we will construct a logistic regression model to assess whether patient and study characteristics influence diagnostic accuracy. DISCUSSION: We believe that this IPD MA will provide the most reliable basis for the assessment of diagnostic accuracy of ONSD ultrasonography for detecting raised ICP and to provide a cutoff value. We also hope that the creation of the ONSD research group will encourage further study. TRIAL REGISTRATION: PROSPERO registration number: CRD42012003072.

Identification of novel and cell type enriched cofactors of the transcription activation domain of RelA (p65 NF-kappaB).

RelA (NF-kappaB) is a transcription factor inducible by distinct stimuli in many different cell types. To find new cell type specific cofactors of NF-kappaB dependent transcription, we isolated RelA transcription activation domain binding proteins from the nuclear extracts of three different cell types. Analysis by electrophoresis and liquid chromatography tandem mass spectrometry identified several novel putative molecular partners. Some were strongly enriched in the complex formed from the nuclear extracts of specific cell types.

A Novel Volume-Age-KPS (VAK) Glioblastoma Classification Identifies a Prognostic Cognate microRNA-Gene Signature.

BACKGROUND: Several studies have established Glioblastoma Multiforme (GBM) prognostic and predictive models based on age and Karnofsky Performance Status (KPS), while very few studies evaluated the prognostic and predictive significance of preoperative MR-imaging. However, to date, there is no simple preoperative GBM classification that also correlates with a highly prognostic genomic signature. Thus, we present for the first time a biologically relevant, and clinically applicable tumor Volume, patient Age, and KPS (VAK) GBM classification that can easily and non-invasively be determined upon patient admission. METHODS: We quantitatively analyzed the volumes of 78 GBM patient MRIs present in The Cancer Imaging Archive (TCIA) corresponding to patients in The Cancer Genome Atlas (TCGA) with VAK annotation. The variables were then combined using a simple 3-point scoring system to form the VAK classification. A validation set (N = 64) from both the TCGA and Rembrandt databases was used to confirm the classification. Transcription factor and genomic correlations were performed using the gene pattern suite and Ingenuity Pathway Analysis. RESULTS: VAK-A and VAK-B classes showed significant median survival differences in discovery (P = 0.007) and validation sets (P = 0.008). VAK-A is significantly associated with P53 activation, while VAK-B shows significant P53 inhibition. Furthermore, a molecular gene signature comprised of a total of 25 genes and microRNAs was significantly associated with the classes and predicted survival in an independent validation set (P = 0.001). A favorable MGMT promoter methylation status resulted in a 10.5 months additional survival benefit for VAK-A compared to VAK-B patients. CONCLUSIONS: The non-invasively determined VAK classification with its implication of VAK-specific molecular regulatory networks, can serve as a very robust initial prognostic tool, clinical trial selection criteria, and important step toward the refinement of genomics-based personalized therapy for GBM patients.

Veille bibliographique sur la surveillance biologique de l'exposition aux produits chimiques en milieu de travail : mise en place d'un réseau francophone multidisciplinaire

L'article présente les étapes de la mise en place d'une veille bibliographique (ou veille scientifique) thématique effectuée conjointement depuis 2005 par 4 institutions francophones du domaine de la santé au travail : l'INRS (France), l'IRSST (Québec), l'IST (Suisse) et l'UCL (Belgique).La thématique suivie est celle de la surveillance biologique de l'exposition aux produits chimiques en milieu de travail. Les données recueillies et mises en forme par les documentalistes servent aux chercheurs spécialistes du sujet non seulement pour suivre les nouveautés du domaine, mais aussi pour documenter des cours et mettre à jour des guides de surveillance biologique. Les différentes étapes de l'approche méthodologique du projet sont décrites : le choix des bases de données à interroger et la mise au point de la stratégie de recherche, la mise en place d'une procédure de partage des tâches pour toutes les étapes du processus de veille qui se répètent à chaque mise à jour (interrogation, création de bases de données avec le logiciel Reference Manager, mise en forme et indexation des références, création et mise à disposition des partenaires des bases de données consolidées au fil du temps avec tous les articles analysés), les moyens administratifs, humains et techniques d'échange de fichiers et les essais pour élargir la veille à la surveillance de pages Web sélectionnées.Un bilan chiffré des six années de la veille est également donné.L'information récoltée et analysée durant les deux dernières années par les partenaires du projet fera l'objet d'un second article axé sur les principales tendances de la thématique choisie.

OpenFluDB, a database for human and animal influenza virus.

Although research on influenza lasted for more than 100 years, it is still one of the most prominent diseases causing half a million human deaths every year. With the recent observation of new highly pathogenic H5N1 and H7N7 strains, and the appearance of the influenza pandemic caused by the H1N1 swine-like lineage, a collaborative effort to share observations on the evolution of this virus in both animals and humans has been established. The OpenFlu database (OpenFluDB) is a part of this collaborative effort. It contains genomic and protein sequences, as well as epidemiological data from more than 27,000 isolates. The isolate annotations include virus type, host, geographical location and experimentally tested antiviral resistance. Putative enhanced pathogenicity as well as human adaptation propensity are computed from protein sequences. Each virus isolate can be associated with the laboratories that collected, sequenced and submitted it. Several analysis tools including multiple sequence alignment, phylogenetic analysis and sequence similarity maps enable rapid and efficient mining. The contents of OpenFluDB are supplied by direct user submission, as well as by a daily automatic procedure importing data from public repositories. Additionally, a simple mechanism facilitates the export of OpenFluDB records to GenBank. This resource has been successfully used to rapidly and widely distribute the sequences collected during the recent human swine flu outbreak and also as an exchange platform during the vaccine selection procedure. Database URL: http://openflu.vital-it.ch.

Identification of CT46/HORMAD1, an immunogenic cancer/testis antigen encoding a putative meiosis-related protein.

Transcripts with ESTs derived exclusively or predominantly from testis, and not from other normal tissues, are likely to be products of genes with testis-restricted expression, and are thus potential cancer/testis (CT) antigen genes. A list of 371 genes with such characteristics was compiled by analyzing publicly available EST databases. RT-PCR analysis of normal and tumor tissues was performed to validate an initial selection of 20 of these genes. Several new CT and CT-like genes were identified. One of these, CT46/HORMAD1, is expressed strongly in testis and weakly in placenta; the highest level of expression in other tissues is <1% of testicular expression. The CT46/HORMAD1 gene was expressed in 31% (34/109) of the carcinomas examined, with 11% (12/109) showing expression levels >10% of the testicular level of expression. CT46/HORMAD1 is a single-copy gene on chromosome 1q21.3, encoding a putative protein of 394 aa. Conserved protein domain analysis identified a HORMA domain involved in chromatin binding. The CT46/HORMAD1 protein was found to be homologous to the prototype HORMA domain-containing protein, Hop1, a yeast meiosis-specific protein, as well as to asy1, a meiotic synaptic mutant protein in Arabidopsis thaliana.

Descriptive epidemiology of Cornelia de Lange syndrome in Europe.

Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome consisting of characteristic dysmorphic features, microcephaly, hypertrichosis, upper limb defects, growth retardation, developmental delay, and a variety of associated malformations. We present a population-based epidemiological study of the classical form of CdLS. The data were extracted from the database of European Surveillance of Congenital Anomalies (EUROCAT) database, a European network of birth defect registries which follow a standard methodology. Based on 23 years of epidemiologic monitoring (8,558,346 births in the 1980-2002 period), we found the prevalence of the classical form of CdLS to be 1.24/100,000 births or 1:81,000 births and estimated the overall CdLS prevalence at 1.6-2.2/100,000. Live born children accounted for 91.5% (97/106) of cases, fetal deaths 2.8% (3/106), and terminations of pregnancy following prenatal diagnosis 5.7% (6/106). The most frequent associated congenital malformations were limb defects (73.1%), congenital heart defects (45.6%), central nervous system malformations (40.2%), and cleft palate (21.7%). In the last 11 years, as much as 68% of cases with major malformations were not detected by routine prenatal US. Live born infants with CdLS have a high first week survival (91.4%). All patients were sporadic. Maternal and paternal age did not seem to be risk factors for CdLS. Almost 70% of patients, born after the 37th week of gestation, weighed <or=2,500 g. Low birth weight correlated with a more severe phenotype. Severe limb anomalies were significantly more often present in males.

Estimation of water retention and availability in soils of Rio Grande do Sul

Dispersed information on water retention and availability in soils may be compiled in databases to generate pedotransfer functions. The objectives of this study were: to generate pedotransfer functions to estimate soil water retention based on easily measurable soil properties; to evaluate the efficiency of existing pedotransfer functions for different geographical regions for the estimation of water retention in soils of Rio Grande do Sul (RS); and to estimate plant-available water capacity based on soil particle-size distribution. Two databases were set up for soil properties, including water retention: one based on literature data (725 entries) and the other with soil data from an irrigation scheduling and management system (239 entries). From the literature database, pedotransfer functions were generated, nine pedofunctions available in the literature were evaluated and the plant-available water capacity was calculated. The coefficient of determination of some pedotransfer functions ranged from 0.56 to 0.66. Pedotransfer functions generated based on soils from other regions were not appropriate for estimating the water retention for RS soils. The plant-available water content varied with soil texture classes, from 0.089 kg kg-1 for the sand class to 0.191 kg kg-1 for the silty clay class. These variations were more related to sand and silt than to clay content. The soils with a greater silt/clay ratio, which were less weathered and with a greater quantity of smectite clay minerals, had high water retention and plant-available water capacity.

The UniProt-GO Annotation database in 2011.

The GO annotation dataset provided by the UniProt Consortium (GOA: http://www.ebi.ac.uk/GOA) is a comprehensive set of evidenced-based associations between terms from the Gene Ontology resource and UniProtKB proteins. Currently supplying over 100 million annotations to 11 million proteins in more than 360,000 taxa, this resource has increased 2-fold over the last 2 years and has benefited from a wealth of checks to improve annotation correctness and consistency as well as now supplying a greater information content enabled by GO Consortium annotation format developments. Detailed, manual GO annotations obtained from the curation of peer-reviewed papers are directly contributed by all UniProt curators and supplemented with manual and electronic annotations from 36 model organism and domain-focused scientific resources. The inclusion of high-quality, automatic annotation predictions ensures the UniProt GO annotation dataset supplies functional information to a wide range of proteins, including those from poorly characterized, non-model organism species. UniProt GO annotations are freely available in a range of formats accessible by both file downloads and web-based views. In addition, the introduction of a new, normalized file format in 2010 has made for easier handling of the complete UniProt-GOA data set.

How to assign a likelihood ratio in a footwear mark case: an analysis and discussion in the light of R v T

This article analyses and discusses issues that pertain to the choice of relevant databases for assigning values to the components of evaluative likelihood ratio procedures at source level. Although several formal likelihood ratio developments currently exist, both case practitioners and recipients of expert information (such as judiciary) may be reluctant to consider them as a framework for evaluating scientific evidence in context. The recent ruling R v T and ensuing discussions in many forums provide illustrative examples for this. In particular, it is often felt that likelihood ratio-based reasoning amounts to an application that requires extensive quantitative information along with means for dealing with technicalities related to the algebraic formulation of these approaches. With regard to this objection, this article proposes two distinct discussions. In a first part, it is argued that, from a methodological point of view, there are additional levels of qualitative evaluation that are worth considering prior to focusing on particular numerical probability assignments. Analyses will be proposed that intend to show that, under certain assumptions, relative numerical values, as opposed to absolute values, may be sufficient to characterize a likelihood ratio for practical and pragmatic purposes. The feasibility of such qualitative considerations points out that the availability of hard numerical data is not a necessary requirement for implementing a likelihood ratio approach in practice. It is further argued that, even if numerical evaluations can be made, qualitative considerations may be valuable because they can further the understanding of the logical underpinnings of an assessment. In a second part, the article will draw a parallel to R v T by concentrating on a practical footwear mark case received at the authors' institute. This case will serve the purpose of exemplifying the possible usage of data from various sources in casework and help to discuss the difficulty associated with reconciling the depth of theoretical likelihood ratio developments and limitations in the degree to which these developments can actually be applied in practice.

Embodied pollution in Spanish household consumption: a disaggregate analysis

[spa] En este artículo aplicamos un modelo input-output ampliado medioambientalmente para analizar un aspecto específico de la hipótesis de la curva de Kuznets ambiental. El propósito del estudio es analizar si las estructuras de consumo de los hogares con una mejor ‘posición económica’ pueden tener un efecto positivo para reducir las presiones medioambientales. Para ello combinamos información de diferentes bases de datos para analizar el impacto de la contaminación atmosférica del consumo de diferentes hogares españoles en el año 2000. Consideramos nueve gases, i.e. los seis gases de efecto invernadero (CO2, CH4, N2O, SF6, HFCs, y PFCs) y otros tres gases (SO2, NOx, y NH3). Clasificamos los hogares en quintiles de gasto per capita y quintiles de gasto equivalente. Los resultados obtenidos muestran que hay una relación positiva y elevada entre el nivel de gasto y las emisiones directas e indirectas generadas por el consumo de los hogares; sin embargo, las intensidades de emisión tienden a disminuir con el nivel de gasto para los diferentes gases, con la excepción de SF6, HFCs, y PFCs.

Rpe65 microarrays, from genes to phosphorylated proteins

Purpose:To describe a novel in silico method to gather and analyze data from high-throughput heterogeneous experimental procedures, i.e. gene and protein expression arrays. Methods:Each microarray is assigned to a database which handles common data (names, symbols, antibody codes, probe IDs, etc.). Links between informations are automatically generated from knowledge obtained in freely accessible databases (NCBI, Swissprot, etc). Requests can be made from any point of entry and the displayed result is fully customizable. Results:The initial database has been loaded with two sets of data: a first set of data originating from an Affymetrix-based retinal profiling performed in an RPE65 knock-out mouse model of Leber's congenital amaurosis. A second set of data generated from a Kinexus microarray experiment done on the retinas from the same mouse model has been added. Queries display wild type versus knock out expressions at several time points for both genes and proteins. Conclusions:This freely accessible database allows for easy consultation of data and facilitates data mining by integrating experimental data and biological pathways.

EGASP: the human ENCODE Genome Annotation Assessment Project.

BACKGROUND: We present the results of EGASP, a community experiment to assess the state-of-the-art in genome annotation within the ENCODE regions, which span 1% of the human genome sequence. The experiment had two major goals: the assessment of the accuracy of computational methods to predict protein coding genes; and the overall assessment of the completeness of the current human genome annotations as represented in the ENCODE regions. For the computational prediction assessment, eighteen groups contributed gene predictions. We evaluated these submissions against each other based on a 'reference set' of annotations generated as part of the GENCODE project. These annotations were not available to the prediction groups prior to the submission deadline, so that their predictions were blind and an external advisory committee could perform a fair assessment. RESULTS: The best methods had at least one gene transcript correctly predicted for close to 70% of the annotated genes. Nevertheless, the multiple transcript accuracy, taking into account alternative splicing, reached only approximately 40% to 50% accuracy. At the coding nucleotide level, the best programs reached an accuracy of 90% in both sensitivity and specificity. Programs relying on mRNA and protein sequences were the most accurate in reproducing the manually curated annotations. Experimental validation shows that only a very small percentage (3.2%) of the selected 221 computationally predicted exons outside of the existing annotation could be verified. CONCLUSION: This is the first such experiment in human DNA, and we have followed the standards established in a similar experiment, GASP1, in Drosophila melanogaster. We believe the results presented here contribute to the value of ongoing large-scale annotation projects and should guide further experimental methods when being scaled up to the entire human genome sequence.

Guidelines for perioperative care after radical cystectomy for bladder cancer: enhanced Recovery After Surgery (ERAS(®)) society recommendations.

PURPOSE: Enhanced recovery after surgery (ERAS) pathways have significantly reduced complications and length of hospital stay after colorectal procedures. This multimodal concept could probably be partially applied to major urological surgery. OBJECTIVES: The primary objective was to systematically assess the evidence of ERAS single items and protocols applied to cystectomy patients. The secondary objective was to address a grade of recommendation to each item, based on the evidence and, if lacking, on consensus opinion from our ERAS Society working group. EVIDENCE ACQUISITION: A systematic literature review was performed on ERAS for cystectomy by searching EMBASE and Medline. Relevant articles were selected and quality-assessed by two independent reviewers using the GRADE approach. If no study specific to cystectomy was available for any of the 22 given items, the authors evaluated whether colorectal guidelines could be extrapolated. EVIDENCE SYNTHESIS: Overall, 804 articles were retrieved from electronic databases. Fifteen articles were included in the present systematic review and 7 of 22 ERAS items were studied. Bowel preparation did not improve outcomes. Early nasogastric tube removal reduced morbidity, bowel recovery time and length of hospital stay. Doppler-guided fluid administration allowed for reduced morbidity. A quicker bowel recovery was observed with a multimodal prevention of ileus, including gum chewing, prevention of PONV and minimally invasive surgery. CONCLUSIONS: ERAS has not yet been widely implemented in urology and evidence for individual interventions is limited or unavailable. The experience in other surgical disciplines encourages the development of an ERAS protocol for cystectomy.