7,692 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

    Resilience and food security in a food systems context

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    This open access book compiles a series of chapters written by internationally recognized experts known for their in-depth but critical views on questions of resilience and food security. The book assesses rigorously and critically the contribution of the concept of resilience in advancing our understanding and ability to design and implement development interventions in relation to food security and humanitarian crises. For this, the book departs from the narrow beaten tracks of agriculture and trade, which have influenced the mainstream debate on food security for nearly 60 years, and adopts instead a wider, more holistic perspective, framed around food systems. The foundation for this new approach is the recognition that in the current post-globalization era, the food and nutritional security of the world’s population no longer depends just on the performance of agriculture and policies on trade, but rather on the capacity of the entire (food) system to produce, process, transport and distribute safe, affordable and nutritious food for all, in ways that remain environmentally sustainable. In that context, adopting a food system perspective provides a more appropriate frame as it incites to broaden the conventional thinking and to acknowledge the systemic nature of the different processes and actors involved. This book is written for a large audience, from academics to policymakers, students to practitioners

    Solidification behavior of high nitrogen stainless steels and establishment of a one-dimensional heat transfer framework

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    Duplex stainless steel (DSS) has excellent corrosion resistance and mechanical properties due to its dual-phase structure. The solidification process is the key to determining the structure of materials, and an in-depth investigation of solidification can help us better understand the properties of materials. The melting and solidification processes of S32101 DSS were investigated using high temperature confocal microscopy (HTCM)

    Impact of language skills and system experience on medical information retrieval

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    An exploration of the language within Ofsted reports and their influence on primary school performance in mathematics: a mixed methods critical discourse analysis

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    This thesis contributes to the understanding of the language of Ofsted reports, their similarity to one another and associations between different terms used within ‘areas for improvement’ sections and subsequent outcomes for pupils. The research responds to concerns from serving headteachers that Ofsted reports are overly similar, do not capture the unique story of their school, and are unhelpful for improvement. In seeking to answer ‘how similar are Ofsted reports’ the study uses two tools, a plagiarism detection software (Turnitin) and a discourse analysis tool (NVivo) to identify trends within and across a large corpus of reports. The approach is based on critical discourse analysis (Van Dijk, 2009; Fairclough, 1989) but shaped in the form of practitioner enquiry seeking power in the form of impact on pupils and practitioners, rather than a more traditional, sociological application of the method. The research found that in 2017, primary school section 5 Ofsted reports had more than half of their content exactly duplicated within other primary school inspection reports published that same year. Discourse analysis showed the quality assurance process overrode variables such as inspector designation, gender, or team size, leading to three distinct patterns of duplication: block duplication, self-referencing, and template writing. The most unique part of a report was found to be the ‘area for improvement’ section, which was tracked to externally verified outcomes for pupils using terms linked to ‘mathematics’. Those required to improve mathematics in their areas for improvement improved progress and attainment in mathematics significantly more than national rates. These findings indicate that there was a positive correlation between the inspection reporting process and a beneficial impact on pupil outcomes in mathematics, and that the significant similarity of one report to another had no bearing on the usefulness of the report for school improvement purposes within this corpus

    A Design Science Research Approach to Smart and Collaborative Urban Supply Networks

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    Urban supply networks are facing increasing demands and challenges and thus constitute a relevant field for research and practical development. Supply chain management holds enormous potential and relevance for society and everyday life as the flow of goods and information are important economic functions. Being a heterogeneous field, the literature base of supply chain management research is difficult to manage and navigate. Disruptive digital technologies and the implementation of cross-network information analysis and sharing drive the need for new organisational and technological approaches. Practical issues are manifold and include mega trends such as digital transformation, urbanisation, and environmental awareness. A promising approach to solving these problems is the realisation of smart and collaborative supply networks. The growth of artificial intelligence applications in recent years has led to a wide range of applications in a variety of domains. However, the potential of artificial intelligence utilisation in supply chain management has not yet been fully exploited. Similarly, value creation increasingly takes place in networked value creation cycles that have become continuously more collaborative, complex, and dynamic as interactions in business processes involving information technologies have become more intense. Following a design science research approach this cumulative thesis comprises the development and discussion of four artefacts for the analysis and advancement of smart and collaborative urban supply networks. This thesis aims to highlight the potential of artificial intelligence-based supply networks, to advance data-driven inter-organisational collaboration, and to improve last mile supply network sustainability. Based on thorough machine learning and systematic literature reviews, reference and system dynamics modelling, simulation, and qualitative empirical research, the artefacts provide a valuable contribution to research and practice

    Neural Architecture Search: Insights from 1000 Papers

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    In the past decade, advances in deep learning have resulted in breakthroughs in a variety of areas, including computer vision, natural language understanding, speech recognition, and reinforcement learning. Specialized, high-performing neural architectures are crucial to the success of deep learning in these areas. Neural architecture search (NAS), the process of automating the design of neural architectures for a given task, is an inevitable next step in automating machine learning and has already outpaced the best human-designed architectures on many tasks. In the past few years, research in NAS has been progressing rapidly, with over 1000 papers released since 2020 (Deng and Lindauer, 2021). In this survey, we provide an organized and comprehensive guide to neural architecture search. We give a taxonomy of search spaces, algorithms, and speedup techniques, and we discuss resources such as benchmarks, best practices, other surveys, and open-source libraries

    A Survey on Biomedical Text Summarization with Pre-trained Language Model

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    The exponential growth of biomedical texts such as biomedical literature and electronic health records (EHRs), provides a big challenge for clinicians and researchers to access clinical information efficiently. To address the problem, biomedical text summarization has been proposed to support clinical information retrieval and management, aiming at generating concise summaries that distill key information from single or multiple biomedical documents. In recent years, pre-trained language models (PLMs) have been the de facto standard of various natural language processing tasks in the general domain. Most recently, PLMs have been further investigated in the biomedical field and brought new insights into the biomedical text summarization task. In this paper, we systematically summarize recent advances that explore PLMs for biomedical text summarization, to help understand recent progress, challenges, and future directions. We categorize PLMs-based approaches according to how they utilize PLMs and what PLMs they use. We then review available datasets, recent approaches and evaluation metrics of the task. We finally discuss existing challenges and promising future directions. To facilitate the research community, we line up open resources including available datasets, recent approaches, codes, evaluation metrics, and the leaderboard in a public project: https://github.com/KenZLuo/Biomedical-Text-Summarization-Survey/tree/master.Comment: 19 pages, 6 figures, TKDE under revie
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