7,517 research outputs found

    UMSL Bulletin 2023-2024

    Get PDF
    The 2023-2024 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1088/thumbnail.jp

    Machine Learning Approaches for the Prioritisation of Cardiovascular Disease Genes Following Genome- wide Association Study

    Get PDF
    Genome-wide association studies (GWAS) have revealed thousands of genetic loci, establishing itself as a valuable method for unravelling the complex biology of many diseases. As GWAS has grown in size and improved in study design to detect effects, identifying real causal signals, disentangling from other highly correlated markers associated by linkage disequilibrium (LD) remains challenging. This has severely limited GWAS findings and brought the method’s value into question. Although thousands of disease susceptibility loci have been reported, causal variants and genes at these loci remain elusive. Post-GWAS analysis aims to dissect the heterogeneity of variant and gene signals. In recent years, machine learning (ML) models have been developed for post-GWAS prioritisation. ML models have ranged from using logistic regression to more complex ensemble models such as random forests and gradient boosting, as well as deep learning models (i.e., neural networks). When combined with functional validation, these methods have shown important translational insights, providing a strong evidence-based approach to direct post-GWAS research. However, ML approaches are in their infancy across biological applications, and as they continue to evolve an evaluation of their robustness for GWAS prioritisation is needed. Here, I investigate the landscape of ML across: selected models, input features, bias risk, and output model performance, with a focus on building a prioritisation framework that is applied to blood pressure GWAS results and tested on re-application to blood lipid traits

    Beam scanning by liquid-crystal biasing in a modified SIW structure

    Get PDF
    A fixed-frequency beam-scanning 1D antenna based on Liquid Crystals (LCs) is designed for application in 2D scanning with lateral alignment. The 2D array environment imposes full decoupling of adjacent 1D antennas, which often conflicts with the LC requirement of DC biasing: the proposed design accommodates both. The LC medium is placed inside a Substrate Integrated Waveguide (SIW) modified to work as a Groove Gap Waveguide, with radiating slots etched on the upper broad wall, that radiates as a Leaky-Wave Antenna (LWA). This allows effective application of the DC bias voltage needed for tuning the LCs. At the same time, the RF field remains laterally confined, enabling the possibility to lay several antennas in parallel and achieve 2D beam scanning. The design is validated by simulation employing the actual properties of a commercial LC medium

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

    Get PDF
    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

    Novel 129Xe Magnetic Resonance Imaging and Spectroscopy Measurements of Pulmonary Gas-Exchange

    Get PDF
    Gas-exchange is the primary function of the lungs and involves removing carbon dioxide from the body and exchanging it within the alveoli for inhaled oxygen. Several different pulmonary, cardiac and cardiovascular abnormalities have negative effects on pulmonary gas-exchange. Unfortunately, clinical tests do not always pinpoint the problem; sensitive and specific measurements are needed to probe the individual components participating in gas-exchange for a better understanding of pathophysiology, disease progression and response to therapy. In vivo Xenon-129 gas-exchange magnetic resonance imaging (129Xe gas-exchange MRI) has the potential to overcome these challenges. When participants inhale hyperpolarized 129Xe gas, it has different MR spectral properties as a gas, as it diffuses through the alveolar membrane and as it binds to red-blood-cells. 129Xe MR spectroscopy and imaging provides a way to tease out the different anatomic components of gas-exchange simultaneously and provides spatial information about where abnormalities may occur. In this thesis, I developed and applied 129Xe MR spectroscopy and imaging to measure gas-exchange in the lungs alongside other clinical and imaging measurements. I measured 129Xe gas-exchange in asymptomatic congenital heart disease and in prospective, controlled studies of long-COVID. I also developed mathematical tools to model 129Xe MR signals during acquisition and reconstruction. The insights gained from my work underscore the potential for 129Xe gas-exchange MRI biomarkers towards a better understanding of cardiopulmonary disease. My work also provides a way to generate a deeper imaging and physiologic understanding of gas-exchange in vivo in healthy participants and patients with chronic lung and heart disease

    Machine learning approach towards predicting turbulent fluid flow using convolutional neural networks

    Get PDF
    Using convolutional neural networks, we present a novel method for predicting turbulent fluid flow through an array of obstacles in this thesis. In recent years, machine learning has exploded in popularity due to its ability to create accurate data driven models and the abundance of available data. In an attempt to understand the characteristics of turbulent fluid flow, we utilise a novel convolutional autoencoder neural network to predict the first ten POD modes of turbulent fluid flow. We find that the model is able to predict the first two POD modes well although and with less accuracy for the remaining eight POD modes. In addition, we find that the ML-predicted POD modes are accurate enough to be used to reconstruct turbulent flow that adequately captures the large-scale details of the original simulation

    Energy Supplies in the Countries from the Visegrad Group

    Get PDF
    The purpose of this Special Issue was to collect and present research results and experiences on energy supply in the Visegrad Group countries. This research considers both macroeconomic and microeconomic aspects. It was important to determine how the V4 countries deal with energy management, how they have undergone or are undergoing energy transformation and in what direction they are heading. The articles concerned aspects of the energy balance in the V4 countries compared to the EU, including the production of renewable energy, as well as changes in its individual sectors (transport and food production). The energy efficiency of low-emission vehicles in public transport and goods deliveries are also discussed, as well as the energy efficiency of farms and energy storage facilities and the impact of the energy sector on the quality of the environment

    Economic and Social Consequences of the COVID-19 Pandemic in Energy Sector

    Get PDF
    The purpose of the Special Issue was to collect the results of research and experience on the consequences of the COVID-19 pandemic for the energy sector and the energy market, broadly understood, that were visible after a year. In particular, the impact of COVID-19 on the energy sector in the EU, including Poland, and the US was examined. The topics concerned various issues, e.g., the situation of energy companies, including those listed on the stock exchange, mining companies, and those dealing with renewable energy. The topics related to the development of electromobility, managerial competences, energy expenditure of local government units, sustainable development of energy, and energy poverty during a pandemic were also discussed

    Measuring the Severity of Depression from Text using Graph Representation Learning

    Get PDF
    The common practice of psychology in measuring the severity of a patient's depressive symptoms is based on an interactive conversation between a clinician and the patient. In this dissertation, we focus on predicting a score representing the severity of depression from such a text. We first present a generic graph neural network (GNN) to automatically rate severity using patient transcripts. We also test a few sequence-based deep models in the same task. We then propose a novel form for node attributes within a GNN-based model that captures node-specific embedding for every word in the vocabulary. This provides a global representation of each node, coupled with node-level updates according to associations between words in a transcript. Furthermore, we evaluate the performance of our GNN-based model on a Twitter sentiment dataset to classify three different sentiments and on Alzheimer's data to differentiate Alzheimer’s disease from healthy individuals respectively. In addition to applying the GNN model to learn a prediction model from the text, we provide post-hoc explanations of the model's decisions for all three tasks using the model's gradients
    • …
    corecore