410 research outputs found

    Computational intelligence approaches to robotics, automation, and control [Volume guest editors]

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    Platelet Diagnostics:A novel liquid biomarker

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    The aim of this thesis is to find a novel liquid biomarker for the detection of cancer and to optimize treatment. The first chapter gives an introduction to the oncology biomarker field and focuses on platelets and their role in cancer. In part 1, we evaluate extracellular vesicles (EVs). EVs are small vesicles released by all types of cells, including tumor cells, into the circulation. They carry protein kinases and can be isolated from plasma. We demonstrate that AKT and ERK kinase protein levels in EVs reflect the cellular expression levels and treatment with kinase inhibitors alters their concentration, depending on the clinical response to the drug. Therefore, EVs may provide a promising biomarker biosource for monitoring of treatment responses. Part 2 starts with reviews describing the function and role of platelets in greater depth. Chapter 3 focusses on thrombocytogenesis and several biological processes in which platelets play a role. Furthermore, the RNA processing machineries harboured by platelets are discussed. Both chapter 3 and 4 evaluate the change platelets undergo after being exposed to tumor and its environment. The exchange of biomolecules with tumor cells results in educated platelets, so-called tumor educated platelets (TEPs). TEPs play a role in several hallmarks of cancer and have the ability to respond to systemic alterations making them an interesting biomarker. In chapter 5 the diagnostic potential of platelets is first discussed. We determine their potential by sequencing the RNA of 283 platelet samples, of which 228 are patients with cancer, and 55 are healthy controls. We reach an accuracy of 96%. Furthermore, we are able to pinpoint the location of the primary tumor with an accuracy of 71%. In part 3, our developed thromboSeq platform is taken to the next level. Several potential confounding factors are taken into account such as age and comorbidity. We show that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels. In a validation cohort we apply these algorithms to non-small-cell lung cancer and reach an accuracy of 88% in late stage (n=518) and early-stage 81% accuracy. Finally, in chapter 7 we describe our wet- and dry-lab protocols in detail. This includes platelet RNA isolation, mRNA amplification, and preparation for next-generation sequencing. The dry-lab protocol describes the automated FASTQ file pre-processing to quantified gene counts, quality controls, data normalization and correction, and swarm intelligence-enhanced support vector machine (SVM) algorithm development. Part 4 focuses on central nervous system (CNS) malignancies especially on glioblastoma. Chapter 8 gives an overview of the different liquid biomarkers for diffuse glioma, the most common primary CNS malignancy. In chapter 9 we assess the specificity of the platelet education due to glioblastoma by comparing the RNA profile of TEPs from glioblastoma patients with a neuroinflammatory disease and brain metastasis patients. This results in a detection accuracy of 80%. Secondly, analysis of patients with glioblastoma versus healthy controls in an independent validation series provide a detection accuracy of 95%. Furthermore, we describe the potential value of platelets as a monitoring biomarker for patients with glioma, distinguishing pseudoprogression from real tumor progression. In part 5 thromboSeq is applied to breast cancer diagnostics both as a screening tool in the general population and in a high risk population, BRCA mutated women. In chapter 11 we first apply our technique to an inflammatory condition, multiple sclerosis (MS). Platelet RNA is used as input for the development of a diagnostic MS classifier capable of detecting MS with 80% accuracy in the independent validation series. In the final part we conclude this thesis with a general discussion of the main findings and suggestions for future research

    Advanced Knowledge Application in Practice

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    The integration and interdependency of the world economy leads towards the creation of a global market that offers more opportunities, but is also more complex and competitive than ever before. Therefore widespread research activity is necessary if one is to remain successful on the market. This book is the result of research and development activities from a number of researchers worldwide, covering concrete fields of research

    Evolutionary Computation

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    This book presents several recent advances on Evolutionary Computation, specially evolution-based optimization methods and hybrid algorithms for several applications, from optimization and learning to pattern recognition and bioinformatics. This book also presents new algorithms based on several analogies and metafores, where one of them is based on philosophy, specifically on the philosophy of praxis and dialectics. In this book it is also presented interesting applications on bioinformatics, specially the use of particle swarms to discover gene expression patterns in DNA microarrays. Therefore, this book features representative work on the field of evolutionary computation and applied sciences. The intended audience is graduate, undergraduate, researchers, and anyone who wishes to become familiar with the latest research work on this field

    Development of benthic monitoring approaches for salmon aquaculture sites using machine learning, hydroacoustic data and bacterial eDNA

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    Intensive caged salmon production can lead to localized perturbations of the seafloor environment where organic waste (flocculent matter) accumulates and disrupts ecological processes. As the aquaculture industry expands, the development of tools to rapidly detect changes in seafloor condition is critical. Here, we examine whether applying machine learning to two types of monitoring data could improve environmental assessments at aquaculture sites in Newfoundland. First, we apply machine learning to single beam echosounder data to detect flocculent matter at aquaculture sites over larger areas than currently achieved used drop camera imaging. Then, we use machine learning to categorize sediments by levels of disturbance based on bacterial tetranucleotide frequency distributions generated from environmental DNA. While echosounder data can detect flocculent matter with moderate success in this region, bacterial tetranucleotide frequencies are highly effective classifiers of benthic disturbance; this simplified environmental DNA-based approach could be implemented within novel aquaculture benthic monitoring pipelines

    Active Materials

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    What is an active material? This book aims to redefine perceptions of the materials that respond to their environment. Through the theory of the structure and functionality of materials found in nature a scientific approach to active materials is first identified. Further interviews with experts from the natural sciences and humanities then seeks to question and redefine this view of materials to create a new definition of active materials

    Novel pattern recognition approaches for transcriptomics data analysis

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    We proposed a family of methods for transcriptomics and genomics data analysis based on multi-level thresholding approach, such as OMTG for sub-grid and spot detection in DNA microarrays, and OMT for detecting significant regions based on next generation sequencing data. Extensive experiments on real-life datasets and a comparison to other methods show that the proposed methods perform these tasks fully automatically and with a very high degree of accuracy. Moreover, unlike previous methods, the proposed approaches can be used in various types of transcriptome analysis problems such as microarray image gridding with different resolutions and spot sizes as well as finding the interacting regions of DNA with a protein of interest using ChIP-Seq data without any need for parameter adjustment. We also developed constrained multi-level thresholding (CMT), an algorithm used to detect enriched regions on ChIP-Seq data with the ability of targeting regions within a specific range. We show that CMT has higher accuracy in detecting enriched regions (peaks) by objectively assessing its performance relative to other previously proposed peak finders. This is shown by testing three algorithms on the well-known FoxA1 Data set, four transcription factors (with a total of six antibodies) for Drosophila melanogaster and the H3K4ac antibody dataset. Finally, we propose a tree-based approach that conducts gene selection and builds a classifier simultaneously, in order to select the minimal number of genes that would reliably predict a given breast cancer subtype. Our results support that this modified approach to gene selection yields a small subset of genes that can predict subtypes with greater than 95%overall accuracy. In addition to providing a valuable list of targets for diagnostic purposes, the gene ontologies of the selected genes suggest that these methods have isolated a number of potential genes involved in breast cancer biology, etiology and potentially novel therapeutics
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