IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis

IMGT/V-QUEST is the highly customized and integrated system for the standardized analysis of the immunoglobulin (IG) and T cell receptor (TR) rearranged nucleotide sequences. IMGT/V-QUEST identifies the variable (V), diversity (D) and joining (J) genes and alleles by alignment with the germline IG and TR gene and allele sequences of the IMGT reference directory. New functionalities were added through a complete rewrite in Java. IMGT/V-QUEST analyses batches of sequences (up to 50) in a single run. IMGT/V-QUEST describes the V-REGION mutations and identifies the hot spot positions in the closest germline V gene. IMGT/V-QUEST can detect insertions and deletions in the submitted sequences by reference to the IMGT unique numbering. IMGT/V-QUEST integrates IMGT/JunctionAnalysis for a detailed analysis of the V-J and V-D-J junctions, and IMGT/Automat for a full V-J- and V-D-J-REGION annotation. IMGT/V-QUEST displays, in ‘Detailed view’, the results and alignments for each submitted sequence individually and, in ‘Synthesis view’, the alignments of the sequences that, in a given run, express the same V gene and allele. The ‘Advanced parameters’ allow to modify default parameters used by IMGT/V-QUEST and IMGT/JunctionAnalysis according to the users’ interest. IMGT/V-QUEST is freely available for academic research at http://imgt.cines.f

Recovering probabilities for nucleotide trimming processes for T cell receptor TRA and TRG V-J junctions analyzed with IMGT tools

<p>Abstract</p> <p>Background</p> <p>Nucleotides are trimmed from the ends of variable (V), diversity (D) and joining (J) genes during immunoglobulin (IG) and T cell receptor (TR) rearrangements in B cells and T cells of the immune system. This trimming is followed by addition of nucleotides at random, forming the N regions (N for nucleotides) of the V-J and V-D-J junctions. These processes are crucial for creating diversity in the immune response since the number of trimmed nucleotides and the number of added nucleotides vary in each B or T cell. IMGT^®sequence analysis tools, IMGT/V-QUEST and IMGT/JunctionAnalysis, are able to provide detailed and accurate analysis of the final observed junction nucleotide sequences (tool "output"). However, as trimmed nucleotides can potentially be replaced by identical N region nucleotides during the process, the observed "output" represents a <it>biased </it>estimate of the "true trimming process."</p> <p>Results</p> <p>A probabilistic approach based on an analysis of the standardized tool "output" is proposed to infer the probability distribution of the "true trimmming process" and to provide plausible biological hypotheses explaining this process. We collated a benchmark dataset of TR alpha (TRA) and TR gamma (TRG) V-J rearranged sequences and junctions analysed with IMGT/V-QUEST and IMGT/JunctionAnalysis, the nucleotide sequence analysis tools from IMGT^®, the international ImMunoGeneTics information system^®, <url>http://imgt.cines.fr</url>. The standardized description of the tool output is based on the IMGT-ONTOLOGY axioms and concepts. We propose a simple first-order model that attempts to transform the observed "output" probability distribution into an estimate closer to the "true trimming process" probability distribution. We use this estimate to test the hypothesis that Poisson processes are involved in trimming. This hypothesis was not rejected at standard confidence levels for three of the four trimming processes: TRAV, TRAJ and TRGV.</p> <p>Conclusion</p> <p>By using trimming of rearranged TR genes as a benchmark, we show that a probabilistic approach, applied to IMGT^®standardized tool "outputs" opens the way to plausible hypotheses on the events involved in the "true trimming process" and eventually to an exact quantification of trimming itself. With increasing high-throughput of standardized immunogenetics data, similar probabilistic approaches will improve understanding of processes so far only characterized by the "output" of standardized tools.</p

IMGT®, the international ImMunoGeneTics information system®

IMGT®, the international ImMunoGeneTics information system® (http://www.imgt.org), was created in 1989 by Marie-Paule Lefranc, Laboratoire d'ImmunoGénétique Moléculaire LIGM (Université Montpellier 2 and CNRS) at Montpellier, France, in order to standardize and manage the complexity of immunogenetics data. The building of a unique ontology, IMGT-ONTOLOGY, has made IMGT® the global reference in immunogenetics and immunoinformatics. IMGT® is a high-quality integrated knowledge resource specialized in the immunoglobulins or antibodies, T cell receptors, major histocompatibility complex, of human and other vertebrate species, proteins of the IgSF and MhcSF, and related proteins of the immune systems of any species. IMGT® provides a common access to standardized data from genome, proteome, genetics and 3D structures. IMGT® consists of five databases (IMGT/LIGM-DB, IMGT/GENE-DB, IMGT/3Dstructure-DB, etc.), fifteen interactive online tools for sequence, genome and 3D structure analysis, and more than 10 000 HTML pages of synthesis and knowledge. IMGT® is used in medical research (autoimmune diseases, infectious diseases, AIDS, leukemias, lymphomas and myelomas), veterinary research, biotechnology related to antibody engineering (phage displays, combinatorial libraries, chimeric, humanized and human antibodies), diagnostics (clonalities, detection and follow-up of residual diseases) and therapeutical approaches (graft, immunotherapy, vaccinology). IMGT is freely available at http://www.imgt.org

Topological signature of deterministic chaos in short nonstationary signals from an optical parametric oscillator

Although deterministic chaos has been predicted to occur in the triply resonant optical parametric oscillator (TROPO) fifteen years ago, experimental evidence of chaotic behavior in this system has been lacking so far, in marked contrast with most nonlinear systems, where chaos has been actively tracked and found. This situation is probably linked to the high sensitivity of the TROPO to perturbations, which adversely affects stationary operation at high power. We report the experimental observation in this system of a burst of irregular behavior of duration 80 microseconds. Although the system is highly nonstationary over this time interval, a topological analysis allows us to extract a clearcut signature of deterministic chaos from a time series segment of only 9 base cycles (3 microseconds). This result suggests that nonstationarity is not necessarily an obstacle to the characterization of chaos

Symbolic dynamical unfolding of spike-adding bifurcations in chaotic neuron models

We characterize the systematic changes in the topological structure of chaotic attractors that occur as spike-adding and homoclinic bifurcations are encountered in the slow-fast dynamics of neuron models. This phenomenon is detailed in the simple Hindmarsh-Rose neuron model, where we show that the unstable periodic orbits appearing after each spike-adding bifurcation are associated with specific symbolic sequences in the canonical symbolic encoding of the dynamics of the system. This allows us to understand how these bifurcations modify the internal structure of the chaotic attractors

Mode hopping strongly affects observability of dynamical instability in optical parametric oscillators

Theoretical investigations of dynamical behavior in optical parametric oscillators (OPO) have generally assumed that the cavity detunings of the interacting fields are controllable parameters. However, OPOs are known to experience mode hops, where the system jumps to the mode of lowest cavity detuning. We note that this phenomenon significantly limits the range of accessible detunings and thus may prevent instabilities predicted to occur above a minimum detuning from being evidenced experimentally. As a simple example among a number of instability mechanisms possibly affected by this limitation, we discuss the Hopf bifurcation leading to periodic behavior in the monomode mean-field model of a triply resonant OPO and show that it probably can be observed only in very specific setups.Comment: submitted to Phys. Rev.

Should We Assess Pituitary Function in Children After a Mild Traumatic Brain Injury? A Prospective Study

The aim of this study was to evaluate the frequency of hypopituitarism following TBI in a cohort of children who had been hospitalized for mild TBI and to identify the predictive factors for this deficiency. A prospective study was conducted on children between 2 and 16 years of age who had been hospitalized for mild TBI according to the Glasgow Coma Scale between September 2009 and June 2013. Clinical parameters, basal pituitary hormone assessment at 0, 6, and 12 months, as well as a dynamic testing (insulin tolerance test) 12 months after TBI were performed. The study included 109 children, the median age was 8.5 years. Patients were examined 6 months ( = 99) and 12 months ( = 96) after TBI. Somatotropic deficiency (defined by a GH peak &lt;20 mUI/l in two tests, an IGF-1 &lt;-1SDS and a delta height &lt;0SDS) were confirmed in 2 cases. One case of gonadotrophic deficiency occurred 1 year after TBI among 13 pubertal children. No cases of precocious puberty, 5 cases of low prolactin level, no cases of corticotropic insufficiency (cortisol peak &lt;500 nmol/l) and no cases diabetes insipidus were recorded. Pituitary insufficiency was present 1year after mild TBI in about 7% of children. Based on our results, we suggest testing children after mild TBI in case of clinical abnormalities. i.e., for GH axis, IGF-1, which should be assessed in children with a delta height &lt;0 SDS, 6 to 12 months after TBI, and a dynamic GH testing (preferentially by an ITT) should be performed in case of IGF-1 &lt;-1SDS, with a GH threshold at 20 mUI/L. However, if a systematic pituitary assessment is not required for mild TBI, physicians should monitor children 1 year after mild TBI with particular attention to growth and weight gain