QiSampler: evaluation of scoring schemes for high-throughput datasets using a repetitive sampling strategy on gold standards

<p>Abstract</p> <p>Background</p> <p>High-throughput biological experiments can produce a large amount of data showing little overlap with current knowledge. This may be a problem when evaluating alternative scoring mechanisms for such data according to a gold standard dataset because standard statistical tests may not be appropriate.</p> <p>Findings</p> <p>To address this problem we have implemented the QiSampler tool that uses a repetitive sampling strategy to evaluate several scoring schemes or experimental parameters for any type of high-throughput data given a gold standard. We provide two example applications of the tool: selection of the best scoring scheme for a high-throughput protein-protein interaction dataset by comparison to a dataset derived from the literature, and evaluation of functional enrichment in a set of tumour-related differentially expressed genes from a thyroid microarray dataset.</p> <p>Conclusions</p> <p>QiSampler is implemented as an open source R script and a web server, which can be accessed at <url>http://cbdm.mdc-berlin.de/tools/sampler/</url>.</p

Food-web structure in relation to environmental gradients and predator-prey ratios in tank-bromeliad ecosystems

Little is known of how linkage patterns between species change along environmental gradients. The small, spatially discrete food webs inhabiting tank-bromeliads provide an excellent opportunity to analyse patterns of community diversity and food-web topology (connectance, linkage density, nestedness) in relation to key environmental variables (habitat size, detrital resource, incident radiation) and predators: prey ratios. We sampled 365 bromeliads in a wide range of understorey environments in French Guiana and used gut contents of invertebrates to draw the corresponding 365 connectance webs. At the bromeliad scale, habitat size (water volume) determined the number of species that constitute food-web nodes, the proportion of predators, and food-web topology. The number of species as well as the proportion of predators within bromeliads declined from open to forested habitats, where the volume of water collected by bromeliads was generally lower because of rainfall interception by the canopy. A core group of microorganisms and generalist detritivores remained relatively constant across environments. This suggests that (i) a highly-connected core ensures food-web stability and key ecosystem functions across environments, and (ii) larger deviations in food-web structures can be expected following disturbance if detritivores share traits that determine responses to environmental changes. While linkage density and nestedness were lower in bromeliads in the forest than in open areas, experiments are needed to confirm a trend for lower food-web stability in the understorey of primary forests

Impact de l'introduction des légumineuses dans les systèmes de culture sur les émissions de protoxyde d'azote

Dans un objectif d'atténuation du réchauffement climatique, la mise en place de systèmes de culture plus autonomes vis - à - vis des engrais minéraux devient incontournable pour réduire les émissions de gaz à effet de serre (GES) tout en diminuant le coût de la fertilisation. L'insertion de légumineuses dans ces systèmes semble être un levier prometteur pour y parvenir. Les économies d'azote permises par différents modes d'introduction de légumineuses et leur impact sur les émissions de GES ont été estimés et évalués en quantifiant au préalable les flux d'azote dans les systèmes avec ou sans légumineuses à partir de données issues de dispositifs expérimentaux préexistants, disponibles dans la bibliographie ou acquises dans de nouveaux essais. L'introduction de légumineuses présente régulièrement un impact positif sur la réduction de l'emploi des engrais azotés. Le risque d'augmentation de la lixiviation du nitrate dépend de leur mode d'introduction et de leur place dans les rotations. Enfin, les émissions mesurées en cul tures principales de légumineuses sont généralement très significativement réduites en comparaison des cultures fertilisées, cependant la dégradation des résidus des légumineuses (en culture ou en couverts) peut générer des émissions de N 2 O corrélées à leur impact sur les flux d'azote, variable selon les conditions pédoclimatiques. Ces résultats devraient permettre d'élaborer des recommandations pour mieux prendre en compte les légumineuses dans la conception de systèmes de culture plus autonomes vis - à - vis des engrais azotés de synthèse et moins émetteurs de N 2 0

NectarCAM : a camera for the medium size telescopes of the Cherenkov Telescope Array

NectarCAM is a camera proposed for the medium-sized telescopes of the Cherenkov Telescope Array (CTA) covering the central energy range of ~100 GeV to ~30 TeV. It has a modular design and is based on the NECTAr chip, at the heart of which is a GHz sampling Switched Capacitor Array and a 12-bit Analog to Digital converter. The camera will be equipped with 265 7-photomultiplier modules, covering a field of view of 8 degrees. Each module includes the photomultiplier bases, high voltage supply, pre-amplifier, trigger, readout and Ethernet transceiver. The recorded events last between a few nanoseconds and tens of nanoseconds. The camera trigger will be flexible so as to minimize the read-out dead-time of the NECTAr chips. NectarCAM is designed to sustain a data rate of more than 4 kHz with less than 5\% dead time. The camera concept, the design and tests of the various subcomponents and results of thermal and electrical prototypes are presented. The design includes the mechanical structure, cooling of the electronics, read-out, clock distribution, slow control, data-acquisition, triggering, monitoring and services.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

A new molecular breast cancer subclass defined from a large scale real-time quantitative RT-PCR study

BACKGROUND: Current histo-pathological prognostic factors are not very helpful in predicting the clinical outcome of breast cancer due to the disease's heterogeneity. Molecular profiling using a large panel of genes could help to classify breast tumours and to define signatures which are predictive of their clinical behaviour. METHODS: To this aim, quantitative RT-PCR amplification was used to study the RNA expression levels of 47 genes in 199 primary breast tumours and 6 normal breast tissues. Genes were selected on the basis of their potential implication in hormonal sensitivity of breast tumours. Normalized RT-PCR data were analysed in an unsupervised manner by pairwise hierarchical clustering, and the statistical relevance of the defined subclasses was assessed by Chi2 analysis. The robustness of the selected subgroups was evaluated by classifying an external and independent set of tumours using these Chi2-defined molecular signatures. RESULTS: Hierarchical clustering of gene expression data allowed us to define a series of tumour subgroups that were either reminiscent of previously reported classifications, or represented putative new subtypes. The Chi2 analysis of these subgroups allowed us to define specific molecular signatures for some of them whose reliability was further demonstrated by using the validation data set. A new breast cancer subclass, called subgroup 7, that we defined in that way, was particularly interesting as it gathered tumours with specific bioclinical features including a low rate of recurrence during a 5 year follow-up. CONCLUSION: The analysis of the expression of 47 genes in 199 primary breast tumours allowed classifying them into a series of molecular subgroups. The subgroup 7, which has been highlighted by our study, was remarkable as it gathered tumours with specific bioclinical features including a low rate of recurrence. Although this finding should be confirmed by using a larger tumour cohort, it suggests that gene expression profiling using a minimal set of genes may allow the discovery of new subclasses of breast cancer that are characterized by specific molecular signatures and exhibit specific bioclinical features

Genetic heterogeneity in hypokalemic periodic paralysis

Abstract Hypokalemic periodic paralysis (hypoPP) is an autosomal dominant disorder belonging to a group of muscle diseases known to involve an abnormal function of ion channels. The latter includes hypokalemic and hyperkalemic periodic paralyses, and non-dystrophic myotonias. We recently showed genetic linkage of hypoPP to loci on chromosome lq31-32, co-localized with the DHP-sensitive calcium channel CACNL1A3. We propose to term this locus hypoPP-1. Using extended haplotypes with new markers located on chromosome lq31-32, we now report the detailed mapping of hypoPP-1 within a 7 cM interval. Two recombinants between hypoPP-1 and the flanking markers D1S413 and D1S510 should help to reduce further the hypoPP-1 interval. We used this new information to demonstrate that a large family of French origin displaying hypoPP is not genetically linked to hypoPP-1. We excluded genetic linkage over the entire hypoPP-1 interval showing for the first time genetic heterogeneity in hypoPE E. Plassart -A. Elbaz. J. V. Santos 9 J. Reboul 9 P. Lapie B. Fontaine ([5~) INSERM U134, H6pital de la Salp~tri6re

Increasing the Number of Thyroid Lesions Classes in Microarray Analysis Improves the Relevance of Diagnostic Markers

BackgroundGenetic markers for thyroid cancers identified by microarray analysis have offered limited predictive accuracy so far because of the few classes of thyroid lesions usually taken into account. To improve diagnostic relevance, we have simultaneously analyzed microarray data from six public datasets covering a total of 347 thyroid tissue samples representing 12 histological classes of follicular lesions and normal thyroid tissue. Our own dataset, containing about half the thyroid tissue samples, included all categories of thyroid lesions. Methodology/Principal Findings Classifier predictions were strongly affected by similarities between classes and by the number of classes in the training sets. In each dataset, sample prediction was improved by separating the samples into three groups according to class similarities. The cross-validation of differential genes revealed four clusters with functional enrichments. The analysis of six of these genes (APOD, APOE, CLGN, CRABP1, SDHA and TIMP1) in 49 new samples showed consistent gene and protein profiles with the class similarities observed. Focusing on four subclasses of follicular tumor, we explored the diagnostic potential of 12 selected markers (CASP10, CDH16, CLGN, CRABP1, HMGB2, ALPL2, ADAMTS2, CABIN1, ALDH1A3, USP13, NR2F2, KRTHB5) by real-time quantitative RT-PCR on 32 other new samples. The gene expression profiles of follicular tumors were examined with reference to the mutational status of the Pax8-PPARγ, TSHR, GNAS and NRAS genes. Conclusion/Significance We show that diagnostic tools defined on the basis of microarray data are more relevant when a large number of samples and tissue classes are used. Taking into account the relationships between the thyroid tumor pathologies, together with the main biological functions and pathways involved, improved the diagnostic accuracy of the samples. Our approach was particularly relevant for the classification of microfollicular adenomas

Rise of oceanographic barriers in continuous populations of a cetacean: the genetic structure of harbour porpoises in Old World waters

<p>Abstract</p> <p>Background</p> <p>Understanding the role of seascape in shaping genetic and demographic population structure is highly challenging for marine pelagic species such as cetaceans for which there is generally little evidence of what could effectively restrict their dispersal. In the present work, we applied a combination of recent individual-based landscape genetic approaches to investigate the population genetic structure of a highly mobile extensive range cetacean, the harbour porpoise in the eastern North Atlantic, with regards to oceanographic characteristics that could constrain its dispersal.</p> <p>Results</p> <p>Analyses of 10 microsatellite loci for 752 individuals revealed that most of the sampled range in the eastern North Atlantic behaves as a 'continuous' population that widely extends over thousands of kilometres with significant isolation by distance (IBD). However, strong barriers to gene flow were detected in the south-eastern part of the range. These barriers coincided with profound changes in environmental characteristics and isolated, on a relatively small scale, porpoises from Iberian waters and on a larger scale porpoises from the Black Sea.</p> <p>Conclusion</p> <p>The presence of these barriers to gene flow that coincide with profound changes in oceanographic features, together with the spatial variation in IBD strength, provide for the first time strong evidence that physical processes have a major impact on the demographic and genetic structure of a cetacean. This genetic pattern further suggests habitat-related fragmentation of the porpoise range that is likely to intensify with predicted surface ocean warming.</p

Applicability and precautions of use of liver injury biomarker FibroTest. A reappraisal at 7 years of age

<p>Abstract</p> <p>Background</p> <p>FibroTest (FT) is a validated biomarker of fibrosis. To assess the applicability rate and to reduce the risk of false positives/negatives (RFPN), security algorithms were developed. The aims were to estimate the prevalence of RFPN and of proven failures, and to identify factors associated with their occurrences.</p> <p>Methods</p> <p>Four populations were studied: 954 blood donors (P1), 7,494 healthy volunteers (P2), 345,695 consecutive worldwide sera (P3), including 24,872 sera analyzed in a tertiary care centre (GHPS) (P4). Analytical procedures of laboratories with RFPN > 5% and charts of P4 patients in with RFPN were reviewed.</p> <p>Results</p> <p>The prevalence of RFPN was 0.52% (5/954; 95%CI 0.17-1.22) in P1, 0.51% (38/7494; 0.36-0.70) in P2, and 0.97% (3349/345695; 0.94-1.00) in P3. Three a priori high-risk populations were confirmed: 1.97% in P4, 1.77% in HIV centre and 2.61% in Sub-Saharan origin subjects. RFPN was mostly associated with low haptoglobin (0.46%), and high apolipoproteinA1 (0.21%). A traceability study of a P3 laboratory with RFPFN > 5% permitted to correct analytical procedures.</p> <p>Conclusion</p> <p>The mean applicability rate of Fibrotest was 99.03%. Independent factors associated with the high risk of false positives/negatives were HIV center, subSaharan origin, and a tertiary care reference centre, although the applicability rate remained above 97%.</p