A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Mesures 3D par caméras CCD de champs de vitesse dans des écoulements turbulents

ST ETIENNE-BU Sciences (422182103) / SudocSudocFranceF

Mesures dans les écoulements par imagerie numérique

National audienceCe dossier traite des mesures dans les écoulements par imagerie numérique. Une première partie est consacrée à la présentation de la dynamique des traceurs dans les écoulements. La technique de Vélocimétrie par images de particules (PIV) est ensuite détaillée ainsi que sa version stéréoscopique (SPIV). Pour finir une nouvelle technique d'analyse en mécanique des fluides, l'holographie numérique, est présentée

Etude tomographique des instabilités d'un jet axisymétrique à bas nombre de Reynolds par PIV et analyse des frontières

L'étude développée dans ce mémoire constitue une contribution par des moyens numériques et expérimentaux à la caractérisation des écoulements de type jet. A partir du développement d'instabilités hydrodynamiques dans un écoulement de type jet axisymétrique libre évoluant à bas nombres de Reynolds, nous avons étudié plus précisément la transition à la turbulence. L'étude numérique consiste à une résolution numérique des équations de Navier-Stockes régissant les écoulements de type jet circulaire et isotherme en régime laminaire. Notre travail a été orienté particulièrement vers l'étude de l'influence des conditions d'émission du gaz à la section d'injection sur le comportement aérodynamique du jet. Nous présentons également des résultats concernant le champ de concentration. Dans la partie expérimentale, la technique de PIV et la visualisation des écoulements associée aux traitements d'images ont été utilisées afin d'étudier le champ de vitesse, les instabilités hydrodynamiques et la transition à la turbulence dans ce type d'écoulements. L'apparition des instabilités, à partir des modes sinueux et variqueux, et leur évolution vers l'état chaotique (turbulent) sont suivies en fonction du paramètre principal à savoir le nombre de Reynolds.The study developed in this memory constitutes a contribution by numerical and experimental means to the characterization of the jet flow type. From the development of hydrodynamic instabilities in a free axisymmetry jet flow evolving at low Reynolds numbers, we more precisely studied the transition to turbulence. The numeric study is relative to a numeric resolution of Navier-Stockes equations governing circular and isotherm jet flow in laminar engine. Our work has been oriented particularly towards the influence of the emission conditions (at the nozzle exit) on the jet aerodynamic behavior. We also present results concerning the concentration field. In the experimental part, the PIV technique and the flow visualization associated with image processing were used to study the velocity field, the hydrodynamic instabilities and the transition to turbulence in this type of flows. In the sinuous and varicose modes, the appearance and of instabilities their evolution towards the chaotic state (turbulent) are followed according to the principal parameter, the Reynolds number.ST ETIENNE-BU Sciences (422182103) / SudocSudocFranceF

Digital Holography compared to Phase Doppler Anemometry: study of an experimental droplet flow

10 pagesInternational audienceHolography is a well-known technique to measure 3D location, velocity, and sizing in a large volume. However it remains not much used in industry because of its experimental complexity. Digital holography has developed because of its ease of use, but the low resolution of the sensors requires it to be partly compensated by image processing techniques. Our new approach for the processing of in-line holograms, based on an inverse problem approach, leads to a significant improvement in axial resolution. We compare the velocity and the size measurements of particles by Digital Holography to the measurements obtained with a standard technique – the Phase Doppler Anemometry. The experimental test consists of the study of a simple low: a monodisperse water droplet flow in air

Digital Holography compared to Phase Doppler Anemometry: study of an experimental droplet flow

10 pagesInternational audienceHolography is a well-known technique to measure 3D location, velocity, and sizing in a large volume. However it remains not much used in industry because of its experimental complexity. Digital holography has developed because of its ease of use, but the low resolution of the sensors requires it to be partly compensated by image processing techniques. Our new approach for the processing of in-line holograms, based on an inverse problem approach, leads to a significant improvement in axial resolution. We compare the velocity and the size measurements of particles by Digital Holography to the measurements obtained with a standard technique – the Phase Doppler Anemometry. The experimental test consists of the study of a simple low: a monodisperse water droplet flow in air