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

Second order sliding-mode observer for estimation of vehicle dynamic parameters

International audienceThis paper uses second-order sliding mode observers to build up an estimation scheme allowing to identify the tyre longitudinal equivalent stiffness and the effective wheel radius using the existing ABS angular sensors. This estimation strategy, based on use of the proposed observer could be used with data acquired experimentally to identify the longitudinal stiffness and effective radius of vehicle tyres. The actual results show effectiveness and robustness of the proposed method

Second Order Sliding-Mode Observer for Estimation of Vehicle Dynamic Parameters

International audienceThis paper uses second-order sliding mode observers to build up an estimation scheme allowing to identify the tire longitudinal equivalent stiffness and the effective wheel radius using the existing ABS angular sensors. This estimation strategy, based on use of the proposed observer could be used with data acquired experimentally to identify the longitudinal stiffness and effective radius of vehicle tires. The actual results show effectiveness and robustness of the proposed method

Second Order Sliding-Mode Observer for Estimation of Vehicle Dynamic Parameters

International audienceThis paper uses second-order sliding mode observers to build up an estimation scheme allowing to identify the tire longitudinal equivalent stiffness and the effective wheel radius using the existing ABS angular sensors. This estimation strategy, based on use of the proposed observer could be used with data acquired experimentally to identify the longitudinal stiffness and effective radius of vehicle tires. The actual results show effectiveness and robustness of the proposed method

Second order sliding-mode observer for estimation of vehicle dynamic parameters

International audienceThis paper uses second-order sliding mode observers to build up an estimation scheme allowing to identify the tyre longitudinal equivalent stiffness and the effective wheel radius using the existing ABS angular sensors. This estimation strategy, based on use of the proposed observer could be used with data acquired experimentally to identify the longitudinal stiffness and effective radius of vehicle tyres. The actual results show effectiveness and robustness of the proposed method

Mechanistic interpretation of braking distance specifications and pavement friction requirements

10.3141/2155-16Transportation Research Record2155145-157TRRE