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

Le comportement de l’entrepreneur: démarche causale, bricolage ou effection ?

Avec 50 contributions, une centaine d'auteurs universitaires, 40 établissements différents et une dizaine de pays représentés, le contenu de ce livre est un ouvrage unique sur le family business. Outil de recherche et de réflexions politiques, il représente une référence à la hauteur du poids économique des PME, soit 2/3 de l'activité, 80 % des emplois créés et la plupart des innovations. Vous y découvrirez les tendances de l'entrepreneuriat avec un « patron » qui, tout en préservant sa qualité essentielle, celle du savoir agir, enrichit sa palette de manager : - il intègre des savoir-faire nouveaux et des méthodes de management originales (l' « effectuation », le crowdfunding, le cloud computing) ; - il s'humanise et devient humaniste avec en outre la prise en compte de la responsabilité sociale et environnementale ; - il cherche à s'appuyer sur la culture de son territoire, sur le made in France et pratique le maillage pour se développer et participer notamment à la ré-industrialisation. Ce livre par le foisonnement des approches traitées et les solutions évoquées vous rendra optimiste

Métaux, pollution de l’air et santé : Les mousses, des alliées originales en épidémiologie

National audienceWhile evidence has accumulated about the links between long-term exposure to air pollution and health, little is known about the health effects of airborne metals. In France, the law makes it mandatory to monitor atmospheric concentrations and deposition of some airborne metals, through measurements or modelling. But the available data are either too scarce or irregular, making them difficult to use in large-scale epidemiology: using mosses in the wild offers a welcome alternative. Mosses belong to the few vegetal organisms able to accumulate airborne metals. As such, they have been used for decades in air quality survey networks in Europe. They provide data to assess population exposure to airborne metals and may complement classical research programmes on air pollution epidemiology. As an example, we estimated associations between exposure to airborne metals of anthropogenic origin and increased mortality in France

Utilisation d’un MOOC et d’une animation 3D interactive en RA pour faciliter la compréhension des mécanismes du climat et de son réchauffement

peer reviewedLes MOOCs (Massive Open Online Course) sont des cours en ligne scénarisés et composés de capsules vidéo-pédagogiques, d’activités pédagogiques variées, de ressources complémentaires ou encore de forums de discussions (Downes, 2008). Ces cours sont proposés gratuitement et massivement sur la plateforme FUN MOOC (https://www.fun-mooc.fr/) mais ils sont aussi ancrés aux cursus des étudiants de l’Université de Liège (Belgique) où ils sont utilisés dans un contexte pédagogique hybride. Le MOOC « Tout comprendre sur le climat et son réchauffement » constitue une aide à la compréhension du fonctionnement du climat, du réchauffement climatique et de ses conséquences. Dans le cadre de ce cours en ligne, une animation 3D interactive en réalité augmentée permettant de visualiser plus clairement la circulation atmosphérique générale et les interconnexions existantes entre les différents constituants impliqués dans le fonctionnement du climat est une véritable innovation techno-pédagogique. Certains phénomènes climatiques plus précis, comme l’effet de Foehn ou les vents catabatiques, profitent même d’une animation 3D interactive spécifique. Cette animation a nécessité une réflexion de fond sur les connaissances et la matière enseignée et son utilisation est d’autant plus facile qu’elle est proposée pour travailler sur n’importe quel terminal que ce soit sur smartphone, tablette ou ordinateur. Les apprenants sont sondés en début et en fin de cours afin de pouvoir évaluer différents indicateurs et réguler le MOOC pour la session suivante

Cloning and embryonic expression pattern of the mouse Onecut transcription factor OC-2

Onecut (OC) transcription factors are evolutionarily conserved proteins with important developmental functions. They contain a bipartite DNA-binding domain composed of a single cut domain associated with a divergent homeodomain. The human genome contains three Onecut paralogues, Hnf6 (also called Oc1), Oc2 and Oc3. We describe here the cloning of mouse (m) OC-2 and its expression pattern in the mouse embryo. The mOc2 gene was localized on chromosome 18. Analysis of the mOC-2 amino acid sequence revealed overall identities of 67% with mHNF-6 and of 56% with mOC-3, and the presence of functional domains delineated earlier in HNF-6. The sequence of the 153 residue-long cut-homeodomain was very conserved, as it was 92% identical to that of mHNF-6 and 89% identical to that of mOC-3. In situ hybridization showed expression of mOc2 in the developing nervous system and gut endoderm. Like Hnf6, Oc2 was expressed in developing liver and pancreas. As many genes that are targeted by Onecut factors are recognized by both OC-2 and HNF-6, this overlap of expression patterns may have functional implications

Kinetics and thermodynamics of interaction of coagulation factor VIII with a pathogenic human antibody

International audienc

A new drone-borne GPR for soil moisture mapping

In this study, we set up a new drone-borne ground-penetrating radar (GPR) for soil moisture mapping. The whole radar system weighs 1.5 kg and consists of a handheld vector network analyzer (VNA) working as frequency domain radar, a lightweight hybrid horn-dipole antenna covering a wide frequency range (250–2800 MHz), a GPS for positioning, a microcomputer with the controlling application, and a smartphone for remote control. Soil moisture is derived from the radar data using full-wave inverse modeling based on the radar equation of Lambot et al. and multilayered media Green's functions. The inversion is performed in the time domain and focuses on the surface reflection. The antenna-drone system is characterized by global reflection and transmission functions which are determined through a calibration procedure. We performed drone-GPR measurements over three different agricultural fields in the loess belt region of Belgium. In this study, we used the 500–700 MHz range to avoid soil surface roughness effects and to focus on the top 10–20 cm of the soil. These fields present a range of landform conditions leading to specific soil moisture distributions. The soil moisture maps were constructed from the local measurements using kriging. The obtained soil moisture maps are in good agreement with the topographical conditions of the fields and aerial orthophotography observations. These results demonstrated the potential and benefits of drone-GPR for fast, high-resolution mapping of soil moisture at the field scale, and to support, e.g., precision agriculture and environmental monitoring