GenOtoScope: Towards automating ACMG classification of variants associated with congenital hearing loss.

Since next-generation sequencing (NGS) has become widely available, large gene panels containing up to several hundred genes can be sequenced cost-efficiently. However, the interpretation of the often large numbers of sequence variants detected when using NGS is laborious, prone to errors and is often difficult to compare across laboratories. To overcome this challenge, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) have introduced standards and guidelines for the interpretation of sequencing variants. Additionally, disease-specific refinements have been developed that include accurate thresholds for many criteria, enabling highly automated processing. This is of particular interest for common but heterogeneous disorders such as hearing impairment. With more than 200 genes associated with hearing disorders, the manual inspection of possible causative variants is particularly difficult and time-consuming. To this end, we developed the open-source bioinformatics tool GenOtoScope, which automates the analysis of all ACMG/AMP criteria that can be assessed without further individual patient information or human curator investigation, including the refined loss of function criterion ("PVS1"). Two types of interfaces are provided: (i) a command line application to classify sequence variants in batches for a set of patients and (ii) a user-friendly website to classify single variants. We compared the performance of our tool with two other variant classification tools using two hearing loss data sets, which were manually annotated either by the ClinGen Hearing Loss Gene Curation Expert Panel or the diagnostics unit of our human genetics department. GenOtoScope achieved the best average accuracy and precision for both data sets. Compared to the second-best tool, GenOtoScope improved the accuracy metric by 25.75% and 4.57% and precision metric by 52.11% and 12.13% on the two data sets, respectively. The web interface is accessible via: http://genotoscope.mh-hannover.de:5000 and the command line interface via: https://github.com/damianosmel/GenOtoScope.

A Reinforcement Learning Approach to View Planning for Automated Inspection Tasks.

Manual inspection of workpieces in highly flexible production facilities with small lot sizes is costly and less reliable compared to automated inspection systems. Reinforcement Learning (RL) offers promising, intelligent solutions for robotic inspection and manufacturing tasks. This paper presents an RL-based approach to determine a high-quality set of sensor view poses for arbitrary workpieces based on their 3D computer-aided design (CAD). The framework extends available open-source libraries and provides an interface to the Robot Operating System (ROS) for deploying any supported robot and sensor. The integration into commonly used OpenAI Gym and Baselines leads to an expandable and comparable benchmark for RL algorithms. We give a comprehensive overview of related work in the field of view planning and RL. A comparison of different RL algorithms provides a proof of concept for the framework's functionality in experimental scenarios. The obtained results exhibit a coverage ratio of up to 0.8 illustrating its potential impact and expandability. The project will be made publicly available along with this article.