Utilizing Multi-level Classification Techniques to Predict Adverse Drug Effects and Reactions

Multi-class classification models are used to predict categorical response variables with more than two possible outcomes. A collection of multi-class classification techniques such as Multinomial Logistic Regression, Na\ {i}ve Bayes, and Support Vector Machine is used in predicting patients’ drug reactions and adverse drug effects based on patients’ demographic and drug administration. The newly released 2018 data on drug reactions and adverse drug effects from U.S. Food and Drug Administration are tested with the models. The applicability of model evaluation measures such as sensitivity, specificity and prediction accuracy in multi-class settings, are also discussed

Lost in translation: Toward a formal model of multilevel, multiscale medicine

For a broad spectrum of low level cognitive regulatory and other biological phenomena, isolation from signal crosstalk between them requires more metabolic free energy than permitting correlation. This allows an evolutionary exaptation leading to dynamic global broadcasts of interacting physiological processes at multiple scales. The argument is similar to the well-studied exaptation of noise to trigger stochastic resonance amplification in physiological subsystems. Not only is the living state characterized by cognition at every scale and level of organization, but by multiple, shifting, tunable, cooperative larger scale broadcasts that link selected subsets of functional modules to address problems. This multilevel dynamical viewpoint has implications for initiatives in translational medicine that have followed the implosive collapse of pharmaceutical industry 'magic bullet' research. In short, failure to respond to the inherently multilevel, multiscale nature of human pathophysiology will doom translational medicine to a similar implosion

Prediction of Voltage Sag Relative Location with Data-Driven Algorithms in Distribution Grid

Power quality (PQ) problems, including voltage sag, flicker, and harmonics, are the main concerns for the grid operator. Among these disturbances, voltage sag, which affects the sensitive loads in the interconnected system, is a crucial problem in the transmission and distribution systems. The determination of the voltage sag relative location as a downstream (DS) and upstream (US) is an important issue that should be considered when mitigating the sag problem. Therefore, this paper proposes a novel approach to determine the voltage sag relative location based on voltage sag event records of the power quality monitoring system (PQMS) in the real distribution system. By this method, the relative location of voltage sag is defined by Gaussian naive Bayes (Gaussian NB) and K-nearest neighbors (K-NN) algorithms. The proposed methods are compared with support vector machine (SVM) and artificial neural network (ANN). The results indicate that K-NN and Gaussian NB algorithms define the relative location of a voltage sag with 98.75% and 97.34% accuracy, respectively

Algorithmic Techniques in Gene Expression Processing. From Imputation to Visualization

The amount of biological data has grown exponentially in recent decades. Modern biotechnologies, such as microarrays and next-generation sequencing, are capable to produce massive amounts of biomedical data in a single experiment. As the amount of the data is rapidly growing there is an urgent need for reliable computational methods for analyzing and visualizing it. This thesis addresses this need by studying how to efficiently and reliably analyze and visualize high-dimensional data, especially that obtained from gene expression microarray experiments. First, we will study the ways to improve the quality of microarray data by replacing (imputing) the missing data entries with the estimated values for these entries. Missing value imputation is a method which is commonly used to make the original incomplete data complete, thus making it easier to be analyzed with statistical and computational methods. Our novel approach was to use curated external biological information as a guide for the missing value imputation. Secondly, we studied the effect of missing value imputation on the downstream data analysis methods like clustering. We compared multiple recent imputation algorithms against 8 publicly available microarray data sets. It was observed that the missing value imputation indeed is a rational way to improve the quality of biological data. The research revealed differences between the clustering results obtained with different imputation methods. On most data sets, the simple and fast k-NN imputation was good enough, but there were also needs for more advanced imputation methods, such as Bayesian Principal Component Algorithm (BPCA). Finally, we studied the visualization of biological network data. Biological interaction networks are examples of the outcome of multiple biological experiments such as using the gene microarray techniques. Such networks are typically very large and highly connected, thus there is a need for fast algorithms for producing visually pleasant layouts. A computationally efficient way to produce layouts of large biological interaction networks was developed. The algorithm uses multilevel optimization within the regular force directed graph layout algorithm.Siirretty Doriast

The era of big data: Genome-scale modelling meets machine learning

With omics data being generated at an unprecedented rate, genome-scale modelling has become pivotal in its organisation and analysis. However, machine learning methods have been gaining ground in cases where knowledge is insufficient to represent the mechanisms underlying such data or as a means for data curation prior to attempting mechanistic modelling. We discuss the latest advances in genome-scale modelling and the development of optimisation algorithms for network and error reduction, intracellular constraining and applications to strain design. We further review applications of supervised and unsupervised machine learning methods to omics datasets from microbial and mammalian cell systems and present efforts to harness the potential of both modelling approaches through hybrid modelling

Local conditions for the decentralization of energy systems

Local energy systems (LES) are designed to decarbonise, balance, and coordinate supply, storage, and demand resources. Which local conditions enable LES to flourish? Using a unique dataset of 146 LES projects in the UK from 2010-2020, we apply econometric methods to identify energy, institutional and socioeconomic conditions significantly associated with LES, but not other local energy forms. We show distributed power generation, low-carbon infrastructure firm activity, local government strategy, and active energy efficiency markets are enablers of LES involving multiple actors, sectors, and skill sets. These conditions describe a clear policy agenda for stimulating and supporting emerging local energy markets

Transcription and splicing regulation in human umbilical vein endothelial cells under hypoxic stress conditions by exon array

<p>Abstract</p> <p>Background</p> <p>The balance between endothelial cell survival and apoptosis during stress is an important cellular process for vessel integrity and vascular homeostasis, and it is also pivotal in angiogenesis during the development of many vascular diseases. However, the underlying molecular mechanisms remain largely unknown. Although both transcription and alternative splicing are important in regulating gene expression in endothelial cells under stress, the regulatory mechanisms underlying this state and their interactions have not yet been studied on a genome-wide basis.</p> <p>Results</p> <p>Human umbilical vein endothelial cells (HUVECs) were treated with cobalt chloride (CoCl₂) both to mimic hypoxia and to induce cell apoptosis and alternative splicing responses. Cell apoptosis rate analysis indicated that HUVECs exposed to 300 μM CoCl₂for 24 hrs were initially counterbalancing apoptosis with cell survival. We therefore used the Affymetrix exon array system to determine genome-wide transcript- and exon-level differential expression. Other than 1583 differentially expressed transcripts, 342 alternatively spliced exons were detected and classified by different splicing types. Sixteen alternatively spliced exons were validated by RT-PCR. Furthermore, direct evidence for the ongoing balance between HUVEC survival and apoptosis was provided by Gene Ontology (GO) and protein function, as well as protein domain and pathway enrichment analyses of the differentially expressed transcripts. Importantly, a novel molecular module, in which the heat shock protein (HSP) families play a significant role, was found to be activated under mimicked hypoxia conditions. In addition, 46% of the transcripts containing stress-modulated exons were differentially expressed, indicating the possibility of combinatorial regulation of transcription and splicing.</p> <p>Conclusion</p> <p>The exon array system effectively profiles gene expression and splicing on the genome-wide scale. Based on this approach, our data suggest that transcription and splicing not only regulate gene expression, but also carry out combinational regulation of the balance between survival and apoptosis of HUVECs under mimicked hypoxia conditions. Since cell survival following the apoptotic challenge is pivotal in angiogenesis during the development of many vascular diseases, our results may advance the knowledge of multilevel gene regulation in endothelial cells under physiological and pathological conditions.</p

Local conditions for the decentralization of energy systems

Local energy systems (LES) are designed to decarbonize, balance, and coordinate supply, storage and demand resources. Which local conditions enable LES to flourish? Using a unique dataset of 146 LES projects in the UK from 2010 to 2020, we apply econometric methods to identify energy, institutional and socio-economic conditions significantly associated with LES, but not other local energy forms. We show distributed power generation, low-carbon infrastructure firm activity, local government strategy and active energy efficiency markets are enablers of LES involving multiple actors, sectors and skill sets. These conditions describe a clear policy agenda for stimulating and supporting emerging local energy markets