428 research outputs found

    Using machine learning to predict pathogenicity of genomic variants throughout the human genome

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    Geschätzt mehr als 6.000 Erkrankungen werden durch Veränderungen im Genom verursacht. Ursachen gibt es viele: Eine genomische Variante kann die Translation eines Proteins stoppen, die Genregulation stören oder das Spleißen der mRNA in eine andere Isoform begünstigen. All diese Prozesse müssen überprüft werden, um die zum beschriebenen Phänotyp passende Variante zu ermitteln. Eine Automatisierung dieses Prozesses sind Varianteneffektmodelle. Mittels maschinellem Lernen und Annotationen aus verschiedenen Quellen bewerten diese Modelle genomische Varianten hinsichtlich ihrer Pathogenität. Die Entwicklung eines Varianteneffektmodells erfordert eine Reihe von Schritten: Annotation der Trainingsdaten, Auswahl von Features, Training verschiedener Modelle und Selektion eines Modells. Hier präsentiere ich ein allgemeines Workflow dieses Prozesses. Dieses ermöglicht es den Prozess zu konfigurieren, Modellmerkmale zu bearbeiten, und verschiedene Annotationen zu testen. Der Workflow umfasst außerdem die Optimierung von Hyperparametern, Validierung und letztlich die Anwendung des Modells durch genomweites Berechnen von Varianten-Scores. Der Workflow wird in der Entwicklung von Combined Annotation Dependent Depletion (CADD), einem Varianteneffektmodell zur genomweiten Bewertung von SNVs und InDels, verwendet. Durch Etablierung des ersten Varianteneffektmodells für das humane Referenzgenome GRCh38 demonstriere ich die gewonnenen Möglichkeiten Annotationen aufzugreifen und neue Modelle zu trainieren. Außerdem zeige ich, wie Deep-Learning-Scores als Feature in einem CADD-Modell die Vorhersage von RNA-Spleißing verbessern. Außerdem werden Varianteneffektmodelle aufgrund eines neuen, auf Allelhäufigkeit basierten, Trainingsdatensatz entwickelt. Diese Ergebnisse zeigen, dass der entwickelte Workflow eine skalierbare und flexible Möglichkeit ist, um Varianteneffektmodelle zu entwickeln. Alle entstandenen Scores sind unter cadd.gs.washington.edu und cadd.bihealth.org frei verfügbar.More than 6,000 diseases are estimated to be caused by genomic variants. This can happen in many possible ways: a variant may stop the translation of a protein, interfere with gene regulation, or alter splicing of the transcribed mRNA into an unwanted isoform. It is necessary to investigate all of these processes in order to evaluate which variant may be causal for the deleterious phenotype. A great help in this regard are variant effect scores. Implemented as machine learning classifiers, they integrate annotations from different resources to rank genomic variants in terms of pathogenicity. Developing a variant effect score requires multiple steps: annotation of the training data, feature selection, model training, benchmarking, and finally deployment for the model's application. Here, I present a generalized workflow of this process. It makes it simple to configure how information is converted into model features, enabling the rapid exploration of different annotations. The workflow further implements hyperparameter optimization, model validation and ultimately deployment of a selected model via genome-wide scoring of genomic variants. The workflow is applied to train Combined Annotation Dependent Depletion (CADD), a variant effect model that is scoring SNVs and InDels genome-wide. I show that the workflow can be quickly adapted to novel annotations by porting CADD to the genome reference GRCh38. Further, I demonstrate the integration of deep-neural network scores as features into a new CADD model, improving the annotation of RNA splicing events. Finally, I apply the workflow to train multiple variant effect models from training data that is based on variants selected by allele frequency. In conclusion, the developed workflow presents a flexible and scalable method to train variant effect scores. All software and developed scores are freely available from cadd.gs.washington.edu and cadd.bihealth.org

    Emerging Power Electronics Technologies for Sustainable Energy Conversion

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    This Special Issue summarizes, in a single reference, timely emerging topics related to power electronics for sustainable energy conversion. Furthermore, at the same time, it provides the reader with valuable information related to open research opportunity niches

    Emerging Power Electronics Technologies for Sustainable Energy Conversion

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    This Special Issue summarizes, in a single reference, timely emerging topics related to power electronics for sustainable energy conversion. Furthermore, at the same time, it provides the reader with valuable information related to open research opportunity niches

    24th Nordic Conference on Computational Linguistics (NoDaLiDa)

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    Design and Implementation of High QoS 3D-NoC using Modified Double Particle Swarm Optimization on FPGA

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    One technique to overcome the exponential growth bottleneck is to increase the number of cores on a processor, although having too many cores might cause issues including chip overheating and communication blockage. The problem of the communication bottleneck on the chip is presently effectively resolved by networks-on-chip (NoC). A 3D stack of chips is now possible, thanks to recent developments in IC manufacturing techniques, enabling to reduce of chip area while increasing chip throughput and reducing power consumption. The automated process associated with mapping applications to form three-dimensional NoC architectures is a significant new path in 3D NoC research. This work proposes a 3D NoC partitioning approach that can identify the 3D NoC region that has to be mapped. A double particle swarm optimization (DPSO) inspired algorithmic technique, which may combine the characteristics having neighbourhood search and genetic architectures, also addresses the challenge of a particle swarm algorithm descending into local optimal solutions. Experimental evidence supports the claim that this hybrid optimization algorithm based on Double Particle Swarm Optimisation outperforms the conventional heuristic technique in terms of output rate and loss in energy. The findings demonstrate that in a network of the same size, the newly introduced router delivers the lowest loss on the longest path.  Three factors, namely energy, latency or delay, and throughput, are compared between the suggested 3D mesh ONoC and its 2D version. When comparing power consumption between 3D ONoC and its electronic and 2D equivalents, which both have 512 IP cores, it may save roughly 79.9% of the energy used by the electronic counterpart and 24.3% of the energy used by the latter. The network efficiency of the 3D mesh ONoC is simulated by DPSO in a variety of configurations. The outcomes also demonstrate an increase in performance over the 2D ONoC. As a flexible communication solution, Network-On-Chips (NoCs) have been frequently employed in the development of multiprocessor system-on-chips (MPSoCs). By outsourcing their communication activities, NoCs permit on-chip Intellectual Property (IP) cores to communicate with one another and function at a better level. The important components in assigning application duties, distributing the work to the IPs, and coordinating communication among them are mapping and scheduling methods. This study aims to present an entirely advanced form of research in the area of 3D NoC mapping and scheduling applications, grouping the results according to various parameters and offering several suggestions for further research

    High Intensity Kaon Experiments (HIKE) at the CERN SPS Proposal for Phases 1 and 2

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    A timely and long-term programme of kaon decay measurements at an unprecedented level of precision is presented, leveraging the capabilities of the CERN Super Proton Synchrotron (SPS). The proposed HIKE programme is firmly anchored on the experience built up studying kaon decays at the SPS over the past four decades, and includes rare processes, CP violation, dark sectors, symmetry tests and other tests of the Standard Model. The programme is based on a staged approach involving experiments with charged and neutral kaon beams, as well as operation in beam-dump mode. The various phases will rely on a common infrastructure and set of detectors.Comment: 147 pages, 82 Figures, 19 Tables. arXiv admin note: text overlap with arXiv:2211.1658

    Micro/Nano Structures and Systems

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    Micro/Nano Structures and Systems: Analysis, Design, Manufacturing, and Reliability is a comprehensive guide that explores the various aspects of micro- and nanostructures and systems. From analysis and design to manufacturing and reliability, this reprint provides a thorough understanding of the latest methods and techniques used in the field. With an emphasis on modern computational and analytical methods and their integration with experimental techniques, this reprint is an invaluable resource for researchers and engineers working in the field of micro- and nanosystems, including micromachines, additive manufacturing at the microscale, micro/nano-electromechanical systems, and more. Written by leading experts in the field, this reprint offers a complete understanding of the physical and mechanical behavior of micro- and nanostructures, making it an essential reference for professionals in this field
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