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International audience; A key challenge for biologists is to document and explain global patterns of diversification in a wide range of environments. Here, we explore patterns of continental-scale diversification in a groundwater species-rich clade, the superfamily Aselloidea (Pancrustacea: Isopoda). Our analyses supported a constant diversification rate during most of the course of Aselloidea evolution, until 4-15 Ma when diversification rates started to decrease. This constant accumulation of lineages challenges the view that groundwater species diversification in temperate regions might have been primarily driven by major changes in physical environment leading to the extinction of surface populations and subsequent synchronous isolation of multiple groundwater populations. Rather than acting synchronously over broad geographic regions, factors causing extinction of surface populations and subsequent reproductive isolation of groundwater populations may act in a local and asynchronous manner, thereby resulting in a constant speciation rate over time. Our phylogeny also revealed several cases of parapatric distributions among closely related surface-water and groundwater species suggesting that species diversification could also arise from a process of disruptive selection along the surface-subterranean environmental gradient. Our results call for re-evaluating the spatial scale and timing of factors causing diversification events in groundwater. [Adaptive shift hypothesis; birth-death-shift model; climatic relict hypothesis; cryptic species; diversification rate; diversification slowdown; molecular timetree; subterranean ecosystems.].

International audience; Perceptual decisions are made when sensory evidence accumulated over time reaches a decision threshold. Because decisions are also guided by prior information, one important factor that is likely to shape how a decision is adaptively tuned to its context is the predictability of forthcoming events. However, little is known about the mechanisms underlying this contextual regulation of the perceptual decision-making process. Mathematical models of decision making predict two possible mechanisms supporting this regulation: an adjustment of the distance to the decision threshold, which leads to a change in the amount of accumulated evidence required to make a decision, or a gain control of the sensory evidence, leading to a change in the slope of the sensory evidence accumulation. Here, we show that predictability of the forthcoming event reduces the distance to the threshold of the decision. Then, combining model-driven fMRI and the framework of information theory, we show that the anterior cingulate cortex (ACC) adjusts the distance to the decision threshold in proportion to the current amount of predictive information and that the dorsolateral cortex (DLPFC) codes the accumulation of sensory evidence. Moreover, the information flow from the ACC to the DLPFC region that accumulates sensory evidence increases when optimal adjustment of the distance to the threshold requires more complex computations, reflecting the increased weight of ACC's regulation signals in the decision process. Our results characterize the respective contributions of the ACC and the DLPFC to contextually optimized decision making.

International audience; The aim of this work was to study the influence of Geant4 parameters on dose distribution and computational time for simulations of carbon ion therapy. The study was done using Geant4 version 9.0. The dose distribution in water for incident monoenergetic carbon ion beams of 300 MeV/u were compared for different values of secondary particle production threshold and different step limits. Variations of depth dose of about 2 mm were observed in some cases, which induced a 30% variation of dose deposit in the Bragg peak region. Other tests were done using Geant4 version 9.2 to verify the results from this study. The two versions provided converging results and led to the same conclusions.

In mammals, several studies have suggested that levels of methylation are higher in repetitive DNA than in nonrepetitive DNA, possibly reflecting a genome-wide defense mechanism against deleterious effects associated with transposable elements (TEs). To analyze the determinants of methylation patterns in primate repetitive DNA, we took advantage of the fact that the methylation rate in the germ line is reflected by the transition rate at CpG sites. We assessed the variability of CpG substitution rates in nonrepetitive DNA and in various TE and retropseudogene families. We show that, unlike other substitution rates, the rate of transition at CpG sites is significantly (37%) higher in repetitive DNA than in nonrepetitive DNA. Moreover, this rate of CpG transition varies according to the number of repeats, their length, and their level of divergence from the ancestral sequence (up to 2.7 times higher in long, lowly divergent TEs compared with unique sequences). This observation strongly suggests the existence of a homology-dependent methylation (HDM) mechanism in mammalian genomes. We propose that HDM is a direct consequence of interfering RNA-induced transcriptional gene silencing.

International audience; The potentially important role of northern microrefugia during postglacial dispersal is challenging the view of southern Europe as a refuge and source area of European biota. In groundwaters, large geographic ranges of presumably good dispersers are increasingly suspected to consist of assemblages of cryptic species with narrow ranges. Moreover, a large species range, even when confirmed by molecular evidence, tells us little about the spatiotemporal dynamics of dispersal. Here, we used phylogenetic inferences, species delineation methods and Bayesian phylogeographic diffusion models to test for the likelihood of postglacial colonization from distant refugia among five morphospecies of Proasellus (Isopoda, Asellidae). All morphospecies except one were monophyletic, but they comprised a total of 15-17 cryptic species. Three cryptic species retained ranges that spanned a distance >650 km, similar to that of the nominal morphospecies. Bayesian diffusion models based on mitochondrial markers revealed considerable spatiotemporal heterogeneity in dispersal rates, suggesting that short-time dispersal windows were instrumental in shaping species ranges. Only one species was found to experience a recent, presumably postglacial, range expansion. The Jura and Alpine foothills probably played a major role in maintaining diversity within Proasel- lus in northern regions by acting both as diversification hotspots and Pleistocene refugia. Gaining insight into the spatiotemporal heterogeneity of dispersal rates revealed contrasting colonization dynamics among species that were not consistent with a global postglacial colonization of Europe from distant refugia.

The Monoceros ring is a collection of stars in nearly-circular orbits at roughly 18 kpc from the Galactic center. It may have originated (i) as the response of the disc to perturbations excited by satellite companions or (ii) from the tidal debris of a disrupted dwarf galaxy. The metallicity of Monoceros stars differs from that of disc stars at comparable Galactocentric distances, an observation that disfavours the first scenario. On the other hand, circular orbits are difficult to accommodate in the tidal-disruption scenario, since it requires a satellite which at the time of disruption was itself in a nearly circular orbit. Such satellite could not have formed at the location of the ring and, given its low mass, dynamical friction is unlikely to have played a major role in its orbital evolution. We search cosmological simulations for low-mass satellites in nearly-circular orbits and find that they result, almost invariably, from orbital changes induced by collisions with more massive satellites: the radius of the circular orbit thus traces the galactocentric distance of the collision. Interestingly, the Sagittarius dwarf, one of the most luminous satellites of the Milky Way, is in a polar orbit that crosses the Galactic plane at roughly the same Galactocentric distance as Monoceros. We use idealized simulations to demonstrate that an encounter with Sagittarius might well have led to the circularization and subsequent tidal demise of the progenitor of the Monoceros ring., Comment: 6 pages, 4 figures, to match version published in MNRAS Letters (http://onlinelibrary.wiley.com/doi/10.1111/j.1745-3933.2011.01035.x/abstract)

International audience; Semantic change has mostly been studied by historical linguists and typically at the scale of centuries. Here we study semantic change at a finer-grained level, the decade, making use of recent newspaper cor- pora. We detect semantic change candidates by observing context shifts which can be triggered by topic salience or may be independent from it. To discriminate these phenomena with accuracy, we combine variation filters with a series of indices which enable building a coherent and flexible semantic change detection model. The indices include widely adaptable tools such as frequency counts, co-occurrence patterns and networks, ranks, as well as model-specific items such as a variability and cohesion mea- sure and graphical representations. The research uses ACOM, a co-occurrence based geometrical model, which is an extension of the Semantic Atlas. Compared to other models of semantic representation, it allows for extremely detailed analysis and provides insight as to how connotational drift processes unfold

International audience; PURPOSE: Four-dimensional computed tomography (4D CT) can provide patient-specific motion information for radiotherapy planning and delivery. Motion estimation in 4D CT is challenging due to the reduced image quality and the presence of artifacts. We aim to improve the robustness of deformable registration applied to respiratory-correlated imaging of the lungs, by using a global problem formulation and pursuing a restrictive parametrization for the spatiotemporal deformation model. METHODS: A spatial transformation based on free-form deformations was extended to the temporal domain, by explicitly modeling the trajectory using a cyclic temporal model based on B-splines. A global registration criterion allowed to consider the entire image sequence simultaneously and enforce the temporal coherence of the deformation throughout the respiratory cycle. To ensure a parametrization capable of capturing the dynamics of respiratory motion, a prestudy was performed on the temporal dimension separately. The temporal parameters were tuned by fitting them to diaphragm motion data acquired for a large patient group. Suitable properties were retained and applied to spatiotemporal registration of 4D CT data. Registration results were validated using large sets of landmarks and compared to consecutive spatial registrations. To illustrate the benefit of the spatiotemporal approach, we also assessed the performance in the presence of motion-induced artifacts. RESULTS: Cubic B-splines gave better or similar fitting results as lower orders and were selected because of their inherently stronger regularization. The fitting and registration errors increased gradually with the temporal control point spacing, representing a trade-off between achievable accuracy and sensitivity to noise and artifacts. A piecewise smooth trajectory model, allowing for a discontinuous change of speed at end-inhale, was found most suitable to account for the sudden changes of motion at this breathing phase. The spatiotemporal modeling allowed a reduction of the number of parameters of 45%, while maintaining registration accuracy within 0.1 mm. The approach reduced the sensitivity to artifacts. CONCLUSIONS: Spatiotemporal registration can provide accurate motion estimation for 4D CT and improves the robustness to artifacts.

International audience; This work proposes a generic method for modeling scanned ion beam delivery systems, without simulation of the treatment nozzle and based exclusively on beam data library (BDL) measurements required for treatment planning systems (TPS). To this aim, new tools dedicated to treatment plan simulation were implemented in the Gate Monte Carlo platform. The method was applied to a dedicated nozzle from IBA for proton pencil beam scanning delivery. Optical and energy parameters of the system were modeled using a set of proton depth-dose profiles and spot sizes measured at 27 therapeutic energies. For further validation of the beam model, specific 2D and 3D plans were produced and then measured with appropriate dosimetric tools. Dose contributions from secondary particles produced by nuclear interactions were also investigated using field size factor experiments. Pristine Bragg peaks were reproduced with 0.7 mm range and 0.2 mm spot size accuracy. A 32 cm range spread-out Bragg peak with 10 cm modulation was reproduced with 0.8 mm range accuracy and a maximum point-to-point dose difference of less than 2%. A 2D test pattern consisting of a combination of homogeneous and high-gradient dose regions passed a 2%/2 mm gamma index comparison for 97% of the points. In conclusion, the generic modeling method proposed for scanned ion beam delivery systems was applicable to an IBA proton therapy system. The key advantage of the method is that it only requires BDL measurements of the system. The validation tests performed so far demonstrated that the beam model achieves clinical performance, paving the way for further studies toward TPS benchmarking. The method involves new sources that are available in the new Gate release V6.1 and could be further applied to other particle therapy systems delivering protons or other types of ions like carbon.

International audience; Fast viral adaptation and the implication of this rapid evolution in the emergence of several new infectious diseases have turned this issue into a major challenge for various research domains. Indeed, viruses are involved in the development of a wide range of pathologies and understanding how viruses and host cells interact in the context of adaptation remains an open question. In order to provide insights into the complex interactions between viruses and their host organisms and namely in the acquisition of novel functions through exchanges of genetic material, we developed the PhEVER database. This database aims at providing accurate evolutionary and phylogenetic information to analyse the nature of virus-virus and virus-host lateral gene transfers. PhEVER (http://pbil.univ-lyon1.fr/databases/phever) is a unique database of homologous families both (i) between sequences from different viruses and (ii) between viral sequences and sequences from cellular organisms. PhEVER integrates extensive data from up-to-date completely sequenced genomes (2426 non-redundant viral genomes, 1007 non-redundant prokaryotic genomes, 43 eukaryotic genomes ranging from plants to vertebrates) and offers a clustering of proteins into homologous families containing at least one viral sequences, as well as alignments and phylogenies for each of these families. Public access to PhEVER is available through its webpage and through all dedicated ACNUC retrieval systems.

International audience; Decision making consists of choosing among available options on the basis of a valuation of their potential costs and benefits. Most theoretical models of decision making in behavioral economics, psychology, and computer science propose that the desirability of outcomes expected from alternative options can be quantified by utility functions. These utility functions allow a decision maker to assign subjective values to each option under consideration by weighting the likely benefits and costs resulting from an action and to select the one with the highest subjective value. Here, we used model-based neuroimaging to test whether the human brain uses separate valuation systems for rewards (erotic stimuli) associated with different types of costs, namely, delay and effort. We show that humans devalue rewards associated with physical effort in a strikingly similar fashion to those they devalue that are associated with delays, and that a single computational model derived from economics theory can account for the behavior observed in both delay discounting and effort discounting. However, our neuroimaging data reveal that the human brain uses distinct valuation subsystems for different types of costs, reflecting in opposite fashion delayed reward and future energetic expenses. The ventral striatum and the ventromedial prefrontal cortex represent the increasing subjective value of delayed rewards, whereas a distinct network, composed of the anterior cingulate cortex and the anterior insula, represent the decreasing value of the effortful option, coding the expected expense of energy. Together, these data demonstrate that the valuation processes underlying different types of costs can be fractionated at the cerebral level.

International audience; When we talk we communicate our intentions. Although the origin of intentional action is debated in cognitive neuroscience, the question of how the brain generates the intention in speech remains still open. Using magnetoencephalography, we investigated the cortical dynamics engaged when healthy subjects attended to either their intention to speak or their actual speech. We found that activity in the right and left parietal cortex increased before subjects became aware of intending to speak. Within the time window of parietal activation, we also observed a transient left frontal activity in Broca's area, a crucial region for inner speech. During attention to speech, neural activity was detected in left prefrontal and temporal areas and in the temporoparietal junction. In agreement with previous results, our findings suggest that the parietal cortex plays a multimodal role in monitoring intentional mechanisms in both action and language. The coactivation of parietal regions and Broca's area may constitute the cortical circuit specific for controlling intentional processes during speech.

International audience; This paper presents an experimental study of application-level Quality of Service (QoS) on the EGEE production grid. Two experiments are reported. First, the design of a Grid Application-Level QoS Service is presented and compared to the DIANE pilot-job framework. Providing dynamic monitoring, the Java Job Submission system is then evaluated in similar conditions. Results show that these systems are able to reach similar QoS than pilot jobs in many cases. However, robustness issues remain and infrastructure monitoring still has to be improved to provide more autonomy to application-level grid job handling systems.

International audience; In this paper, we will show how iRODS is being usedd at CC-IN2P3, the future plans, code development, and also SRB to iRODS migration

Background Comparative genomics is a central step in many sequence analysis studies, from gene annotation and the identification of new functional regions in genomes, to the study of evolutionary processes at the molecular level (speciation, single gene or whole genome duplications, etc.) and phylogenetics. In that context, databases providing users high quality homologous families and sequence alignments as well as phylogenetic trees based on state of the art algorithms are becoming indispensable. Methods We developed an automated procedure allowing massive all-against-all similarity searches, gene clustering, multiple alignments computation, and phylogenetic trees construction and reconciliation. The application of this procedure to a very large set of sequences is possible through parallel computing on a large computer cluster. Results Three databases were developed using this procedure: HOVERGEN, HOGENOM and HOMOLENS. These databases share the same architecture but differ in their content. HOVERGEN contains sequences from vertebrates, HOGENOM is mainly devoted to completely sequenced microbial organisms, and HOMOLENS is devoted to metazoan genomes from Ensembl. Access to the databases is provided through Web query forms, a general retrieval system and a client-server graphical interface. The later can be used to perform tree-pattern based searches allowing, among other uses, to retrieve sets of orthologous genes. The three databases, as well as the software required to build and query them, can be used or downloaded from the PBIL (Pôle Bioinformatique Lyonnais) site at http://pbil.univ-lyon1.fr/.

We have assessed behavioural and environmental factors influencing the success of global positioning system (GPS) fixes recorded from 15 collared free-ranging female Mediterranean mouflon (Ovis gmelini musimon x Ovis sp.). We have demonstrated that fix success was 8% lower in resting animals (0.81, 95% CI = 0.79–0.84) than in active animals (0.89, 95% CI = 0.86–0.91) at an average temperature (13.8°C), but was similar and relatively constant at lower temperatures. When temperatures increased above the average temperature, fix success strongly decreased in resting animals (0.44, 95% CI = 0.36–0.52 at 30°C) as compared to active animals (0.76, 95% CI = 0.65–0.85). These results probably involved behavioural changes in habitat use of mouflon, as temperature and activity strongly influence the use of cover in ungulates. We also found that the success of GPS fixes was influenced by habitat types, increasing from 0.76 to 0.93 (under average sky openness of 33%) along a continuum going from forested to open areas. After controlling for differences in vegetation, sky openness had a positive effect on fix success (from 0.76 to 0.97 in evergreen oak forest). Our approach based on free-ranging animals and using a robust interpolation procedure should provide biologists with a more reliable method to account for bias in GPS studies.

In seasonal environments, timing of reproduction is an important fitness component. However, in ungulates, our understanding of this biological process is limited. Here we analyze how age and body mass affect spatiotemporal variation in timing of ovulation of 6,178 Norwegian moose. We introduced a parametric statistical model to obtain inferences about the seasonal timing of ovulation peak, the degree of synchrony among individuals, and the proportion of individuals that ovulate. These components showed much more spatiotemporal variation than previously reported. Young (primiparous) and old (> or =11.5 years of age) females ovulated later than prime-aged (2.5-10.5 years of age) females. In all age classes, ovulation was delayed with decreasing body mass. Ovulation rates were lower and more variable among primiparous females than among older females. Young females required higher body mass than older females did to ovulate. The body-mass-to-ovulation relationship varied with age, showed large regional variation, and differed among years within region. These results suggest that (1) environmental and population characteristics contribute to shape seasonal variation in the breeding pattern and (2) large regional variation exists in the size-dependent age at maturity in moose. Hence, the life-history trade-off between reproduction and body growth should differ regionally in moose.

International audience; PURPOSE: We propose a new method for efficient particle transportation in voxelized geometry for Monte Carlo simulations. We describe its use for calculating dose distribution in CT images for radiation therapy. MATERIAL AND METHODS: The proposed approach, based on an implicit volume representation named segmented volume, coupled with an adapted segmentation procedure and a distance map, allows us to minimize the number of boundary crossings, which slows down simulation. The method was implemented with the GEANT4 toolkit and compared to four other methods: One box per voxel, parameterized volumes, octree-based volumes, and nested parameterized volumes. For each representation, we compared dose distribution, time, and memory consumption. RESULTS: The proposed method allows us to decrease computational time by up to a factor of 15, while keeping memory consumption low, and without any modification of the transportation engine. Speeding up is related to the geometry complexity and the number of different materials used. We obtained an optimal number of steps with removal of all unnecessary steps between adjacent voxels sharing a similar material. However, the cost of each step is increased. When the number of steps cannot be decreased enough, due for example, to the large number of material boundaries, such a method is not considered suitable. CONCLUSION: This feasibility study shows that optimizing the representation of an image in memory potentially increases computing efficiency. We used the GEANT4 toolkit, but we could potentially use other Monte Carlo simulation codes. The method introduces a tradeoff between speed and geometry accuracy, allowing computational time gain. However, simulations with GEANT4 remain slow and further work is needed to speed up the procedure while preserving the desired accuracy.

Background "Open" transcriptome analysis methods allow to study gene expression without a priori knowledge of the transcript sequences. As of now, SAGE (Serial Analysis of Gene Expression), LongSAGE and MPSS (Massively Parallel Signature Sequencing) are the mostly used methods for "open" transcriptome analysis. Both LongSAGE and MPSS rely on the isolation of 21 pb tag sequences from each transcript. In contrast to LongSAGE, the high throughput sequencing method used in MPSS enables the rapid sequencing of very large libraries containing several millions of tags, allowing deep transcriptome analysis. However, a bias in the complexity of the transcriptome representation obtained by MPSS was recently uncovered. Results In order to make a deep analysis of mouse hypothalamus transcriptome avoiding the limitation introduced by MPSS, we combined LongSAGE with the Solexa sequencing technology and obtained a library of more than 11 millions of tags. We then compared it to a LongSAGE library of mouse hypothalamus sequenced with the Sanger method. Conclusion We found that Solexa sequencing technology combined with LongSAGE is perfectly suited for deep transcriptome analysis. In contrast to MPSS, it gives a complex representation of transcriptome as reliable as a LongSAGE library sequenced by the Sanger method.

International audience; In this article, our goal is twofold. First, we propose and compare two methods which process deformable registration to estimate patient specific lung and tumor displacements and deformation during free breathing from four-dimensional computed tomography (4D-CT) data. Second, we propose techniques to quantify the physiological parameters of motion nonlinearity and hysteresis. A Fréchet distance-based criterion is introduced to measure the motion hysteresis. Experiments were conducted with 4D-CT data of five patients treated in radiotherapy for non-small cell lung cancer. The accuracy of deformation fields assessed against expert-selected landmarks was found to be within image voxel tolerance. The second method gave slightly better results in terms of accuracy and consistency, although the differences were not statistically significant between the two methods. Lung motion nonlinearity and hysteresis are patient specific, and vary across regions within the lung during respiration. For all patients, motion between end-exhale and end-inhale was well approximated with a straight line trajectory for the majority of lung points. Hysteresis was found to be globally correlated with trajectory length. The main limitation to the proposed method is that intensity-based deformable registration is dependent on image quality and image resolution. Another limitation is the absence of gold standard which makes the validation of the computed motion difficult. However, the proposed tools provide patient specific motion information which, in radiotherapy for example, can ease the definition of precise internal margins. In the future, the integration of physiological information from multiple patients could help to create a general lung atlas with different clinical applications.

International audience; A hybrid approach was developed to compute the dose deposited in cancerous and healthy tissues during stereotactic synchrotron radiation therapy treatment. The proposed approach divides the computation into two parts: (1) the dose deposited by primary radiation (coming directly from the incident X-ray beam) is calculated using a deterministic algorithm based on ray casting, optimized for transport in voxelized geometries; (2) the dose deposited by secondary radiation (Rayleigh and Compton scattering, fluorescence) is computed using a hybrid algorithm combining Monte Carlo and deterministic calculations. In the Monte Carlo part, a set of scattering and fluorescence events occurring in the patient is determined. These events are further processed in a deterministic way, which considerably improves the statistics of the final dose map. The results obtained in test cases are compared to those obtained with the Monte Carlo method alone (Geant4 and MCNPX codes) and found to be in excellent agreement. The proposed simulation scheme makes it possible to simulate dose maps with a single PC, featuring computation time and statistical fluctuations substantially reduced in comparison with full Monte Carlo simulations.

A general feature of the demography of large ungulates is that many demographic traits are dependent on female body mass at early ages. Thus, identifying the factors affecting body mass variation can give important mechanistic understanding of demographic processes. Here we relate individual variation in autumn and winter body mass of moose calves living at low density on an island in northern Norway to characteristics of their mother, and examine how these relationships are affected by annual variation in population density and climate. Body mass increased with increasing age of their mother, was lower for calves born late in the spring, decreased with litter size and was larger for males than for female calves. No residual effects of variation in density and climate were present after controlling for annual variation in mother age and calving date. The annual variation in adult female age structure and calving date explained a large part (71–75%) of the temporal variation in calf body mass. These results support the hypotheses that (a) body mass of moose calves are affected by qualities associated with mother age (e.g. body condition, calving date); and (b) populations living at low densities are partly buffered against temporal fluctuations in the environment.

We propose an extension of the classical morphological filtering based on openings by line segment structuring elements. It consists in filtering a 3D+time image with the opening by all the possible rotations of a segment in the 4D space, given an initial segment and a rotation angle. The method has been applied to remove noise from confocal laser scanning microscopy images of live zebrafish embryos engineered to fluorescently label all their cell membranes.

Processed pseudogenes result from reverse transcribed mRNAs. In general, because processed pseudogenes lack promoters, they are no longer functional from the moment they are inserted into the genome. Subsequently, they freely accumulate substitutions, insertions and deletions. Moreover, the ancestral structure of processed pseudogenes could be easily inferred using the sequence of their functional homologous genes. Owing to these characteristics, processed pseudogenes represent good neutral markers for studying genome evolution. Recently, there is an increasing interest for these markers, particularly to help gene prediction in the field of genome annotation, functional genomics and genome evolution analysis (patterns of substitution). For these reasons, we have developed a method to annotate processed pseudogenes in complete genomes. To make them useful to different fields of research, we stored them in a nucleic acid database after having annotated them. In this work, we screened both mouse and human complete genomes from ENSEMBL to find processed pseudogenes generated from functional genes with introns. We used a conservative method to detect processed pseudogenes in order to minimize the rate of false positive sequences. Within processed pseudogenes, some are still having a conserved open reading frame and some have overlapping gene locations. We designated as retroelements all reverse transcribed sequences and more strictly, we designated as processed pseudogenes, all retroelements not falling in the two former categories (having a conserved open reading or overlapping gene locations). We annotated 5823 retroelements (5206 processed pseudogenes) in the human genome and 3934 (3428 processed pseudogenes) in the mouse genome. Compared to previous estimations, the total number of processed pseudogenes was underestimated but the aim of this procedure was to generate a high-quality dataset. To facilitate the use of processed pseudogenes in studying genome structure and evolution, DNA sequences from processed pseudogenes, and their functional reverse transcribed homologs, are now stored in a nucleic acid database, HOPPSIGEN. HOPPSIGEN can be browsed on the PBIL (Pôle Bioinformatique Lyonnais) World Wide Web server (http://pbil.univ-lyon1.fr/) or fully downloaded for local installation.

Integr8 is a new web portal for exploring the biology of organisms with completely deciphered genomes. For over 190 species, Integr8 provides access to general information, recent publications, and a detailed statistical overview of the genome and proteome of the organism. The preparation of this analysis is supported through Genome Reviews, a new database of bacterial and archaeal DNA sequences in which annotation has been upgraded (compared to the original submission) through the integration of data from many sources, including the EMBL Nucleotide Sequence Database, the UniProt Knowledgebase, InterPro, CluSTr, GOA and HOGENOM. Integr8 also allows the users to customize their own interactive analysis, and to download both customized and prepared datasets for their own use. Integr8 is available at http://www.ebi.ac.uk/integr8.

International audience; OBJECTIVES: Hospitals and medical centers are producing more and more data that need to be processed. Those data are confidential, heterogeneous, and limited to the geographic site where they have been produced. Unless properly anonymized, they cannot be distributed on wide area networks. METHODS: Grid technologies allow the globalization of storage and processing resources, and enable large-scale experimentations on distributed data. They constitute a promising tool to treat the different data and analyze the knowledge they contain, while offering secured access and high-performance computing capacities to the different users. Our aim is to evaluate the possibilities of grid technologies for handling medical data. RESULTS AND CONCLUSIONS: In this paper, we focus on a breast cancer diagnosis assistance tool, based on distributed and incremental knowledge construction and a content-based image retrieval system. We analyze the different scenarios of uses of such a tool. We further propose an algorithm that indexes mammographic images for content-based query purposes. This algorithm is tested on images of different resolutions in order to reduce the indexation time and we analyze its performance with experiments on the grid.

Rheumatoid arthritis (RA) is a heterogeneous disease that exhibits a complex genetic component. Previous RA genome scans confirmed the involvement of the HLA region and generated data on suggestive signals at non-HLA regions, albeit with few overlaps in findings between studies. The present study was undertaken to detect potential RA gene regions and to estimate the number of true RA gene regions, taking into account the heterogeneity of RA, through performance of a dense genome scan.In a study of 88 French Caucasian families (105 RA sibpairs), 1,088 microsatellite markers were genotyped (3.3-cM genome scan), and a multipoint model-free linkage analysis was performed. The statistical assessment of the results relied on 10,000 computer simulations. A covariate-based multipoint model-free linkage analysis was performed on the locations of regions with suggestive evidence for linkage.Involvement of the HLA region was strongly confirmed (P = 6 x 10(-5)), and 19 non-HLA regions showed suggestive evidence for linkage (P0.05); 9 of these overlapped with regions suggested in other published RA genome scans. A routine 12-cM genome scan with the same families would have detected only 7 of the 19 regions, including only 4 of the 9 overlapping regions. From the 10,000 computer simulations, we estimated that 8 +/- 4 regions (mean +/- SD) were true-positives. RA covariate-based analysis provided additional linkage evidence for 3 regions, with age at disease onset, erosions, and HLA-DRB1 shared epitope as covariates.The results of this study provide evidence of 19 non-HLA RA gene regions, with an estimate of 8 +/- 4 as true-positives, and provide additional evidence for 3 regions from covariate-based analysis.

International audience; Streptococcus pyogenes, is an important human pathogen classified within the pyogenic group of streptococci, exclusively adapted to the human host. Our goal was to employ a comparative evolutionary approach to better understand the genomic events concomitant with S. pyogenes human adaptation. As part of ascertaining these events, we sequenced the genome of one of the potential sister species, the agricultural pathogen S. canis, and combined it in a comparative genomics reconciliation analysis with two other closely related species, Streptococcus dysgalactiae and Streptococcus equi, to determine the genes that were gained and lost during S. pyogenes evolution. Genome wide phylogenetic analyses involving 15 Streptococcus species provided convincing support for a clade of S. equi, S. pyogenes, S. dysgalactiae, and S. canis and suggested that the most likely S. pyogenes sister species was S. dysgalactiae. The reconciliation analysis identified 113 genes that were gained on the lineage leading to S. pyogenes. Almost half (46%) of these gained genes were phage associated and 14 showed significant matches to experimentally verified bacteria virulence factors. Subsequent to the origin of S. pyogenes, over half of the phage associated genes were involved in 90 different LGT events, mostly involving different strains of S. pyogenes, but with a high proportion involving the horse specific pathogen S. equi subsp. equi, with the directionality almost exclusively (86%) in the S. pyogenes to S. equi direction. Streptococcus agalactiae appears to have played an important role in the evolution of S. pyogenes with a high proportion of LGTs originating from this species. Overall the analysis suggests that S. pyogenes adaptation to the human host was achieved in part by (i) the integration of new virulence factors (e.g. speB, and the sal locus) and (ii) the construction of new regulation networks (e.g. rgg, and to some extent speB).

International audience; Large scale phylogenomics and comparative genomics require complex computational methods (parsimony, maximum likelihood, bayesian methods, MCMC, etc.) associated with massively distributed calculation. In this respect, grid computing plays a crucial role. Here we present how we processed exhaustive similarity searches on several millions of sequences with BLAST, using two different grids (TIDRA and GRISBI).