image analysis and processing with applications in proteomics and medicine

This thesis introduces unsupervised image analysis algorithms for the segmentation of several types of images, with an emphasis on proteomics and medical images. Τhe presented algorithms are tailored upon the principles of deformable models and more specific region-based active contours. Two different objectives are pursued. The first is the core issue of unsupervised parameterization in image segmentation, whereas the second is the formulation of a complete model for the segmentation of proteomics images, which is the first to exploit the appealing attributes of active contours. The first major contribution of this thesis is a novel framework for the automated parameterization of region-based active contours. The presented framework aims to endow segmentation results with objectivity and robustness as well as to set domain users free from the cumbersome and time-consuming process of empirical adjustment. It is applicable on various medical imaging modalities and remains insensitive on alterations in the settings of the acquisition devices. The experimental results demonstrate that the presented framework maintains a segmentation quality which is comparable to the one obtained with empirical parameterization. The second major contribution of this thesis is an unsupervised active contour-based model for the segmentation of proteomics images. The presented model copes with crucial issues in 2D-GE image analysis including streaks, artifacts, faint and overlapping spots. In addition, it provides an alternate to the laborious, error-prone process of manual editing, which is required in state-of-the-art 2D-GE image analysis software packages. The experimental results demonstrate that the presented model outperforms 2D-GE image analysis software packages in terms of detection and segmentation quantity metrics

Image Analysis and Processing With Applications in Proteomics and Medicine

Στην παρούσα διατριβή παρουσιάζονται αυτόματοι αλγόριθμοι ανάλυσης εικόνας για την κατάτμηση διαφόρων τύπων εικόνων, με έμφαση στις εικόνες πρωτεομικής και στις ιατρικές εικόνες. Οι προτεινόμενοι αλγόριθμοι βασίζονται στις αρχές των παραμορφώσιμων μοντέλων. Η διατριβή εστιάζει σε δύο κυρίως στόχους: 1) στην επίλυση του σημαντικού προβλήματος της αυτόματης παραμετροποίησης στην κατάτμηση εικόνας, 2) στην διατύπωση ενός ολοκληρωμένου μοντέλου κατάτμησης εικόνων πρωτεομικής. Η πρώτη συνεισφορά είναι ένα πρωτότυπο πλαίσιο αυτόματης παραμετροποίησης των ενεργών περιγραμμάτων περιοχής. Το πλαίσιο εμπλουτίζει τα αποτελέσματα με αντικειμενικότητα και απελευθερώνει τους τελικούς χρήστες από την επίπονη διαδικασία της εμπειρικής ρύθμισης. Εφαρμόζεται σε διάφορους τύπους ιατρικών εικόνων και παραμένει ανεπηρέαστο στις τροποποιήσεις των ρυθμίσεων των συσκευών λήψης των εικόνων αυτών. Τα πειραματικά αποτελέσματα καταδεικνύουν ότι το προτεινόμενο πλαίσιο διατηρεί υψηλή την ποιότητα κατάτμησης, συγκρίσιμη με εκείνη που επιτυγχάνεται με εμπειρική παραμετροποίηση. Η δεύτερη συνεισφορά είναι ένα αυτόματο μοντέλο βασιζόμενο στα ενεργά περιγράμματα για την κατάτμηση εικόνων πρωτεομικής. Το μοντέλο αντιμετωπίζει σημαντικά προβλήματα συμπεριλαμβανομένων των γραμμών, τεχνουργημάτων, αχνών και επικαλυπτομένων κηλίδων. Ακόμη, παρέχει εναλλακτική λύση στην επιρρεπή σε σφάλματα διαδικασία της χειρωνακτικής επεξεργασίας που απαιτείται στα υπάρχοντα πακέτα λογισμικού. Τα πειραματικά αποτελέσματα καταδεικνύουν ότι το προτεινόμενο μοντέλο υπερτερεί των υπαρχόντων πακέτων λογισμικού σε ποσοτικές μετρικές εντοπισμού και κατάτμησης.This thesis introduces unsupervised image analysis algorithms for the segmentation of several types of images, with an emphasis on proteomics and medical images. Τhe presented algorithms are tailored upon the principles of deformable models. Two objectives are pursued: 1) the core issue of unsupervised parameterization in image segmentation, 2) the formulation of a complete model for the segmentation of proteomics images. The first contribution is a novel framework for automated parameterization of region-based active contours. The presented framework endows segmentation results with objectivity and sets domain users free from the cumbersome process of empirical adjustment. It is applicable on various medical imaging modalities and remains insensitive on alterations in the settings of acquisition devices. The experimental results demonstrate that the presented framework maintains a high segmentation quality, comparable to the one obtained with empirical parameterization. The second contribution is an unsupervised active contour-based model for the segmentation of proteomics images. The presented model copes with crucial issues including streaks, artifacts, faint and overlapping spots. Moreover, it provides an alternate to the error-prone process of manual editing, required in state-of-the-art software packages. The experimental results demonstrate that the proposed model outperforms software packages in terms of detection and segmentation quantity metrics

Chemometrics for ion mobility spectrometry data:Recent advances and future prospects

Contains fulltext : 161386.pdf (publisher's version ) (Open Access)Historically, advances in the field of ion mobility spectrometry have been hindered by the variation in measured signals between instruments developed by different research laboratories or manufacturers. This has triggered the development and application of chemometric techniques able to reveal and analyze precious information content of ion mobility spectra. Recent advances in multidimensional coupling of ion mobility spectrometry to chromatography and mass spectrometry has created new, unique challenges for data processing, yielding high-dimensional, megavariate datasets. In this paper, a complete overview of available chemometric techniques used in the analysis of ion mobility spectrometry data is given. We describe the current state-of-the-art of ion mobility spectrometry data analysis comprising datasets with different complexities and two different scopes of data analysis, i.e. targeted and non-targeted analyte analyses. Two main steps of data analysis are considered: data preprocessing and pattern recognition. A detailed description of recent advances in chemometric techniques is provided for these steps, together with a list of interesting applications. We demonstrate that chemometric techniques have a significant contribution to the recent and great expansion of ion mobility spectrometry technology into different application fields. We conclude that well-thought out, comprehensive data analysis strategies are currently emerging, including several chemometric techniques and addressing different data challenges. In our opinion, this trend will continue in the near future, stimulating developments in ion mobility spectrometry instrumentation even further

Interpretation of comprehensive two-dimensional gas chromatography data using advanced chemometrics

The power of comprehensive two-dimensional gas chromatography (GC × GC) for the study of complex mixtures has been indisputably proved in the past several decades. This review encompasses the whole of GC × GC-related data processing and summarizes relevant applications. We include theoretical introduction to some specific methods and studies to aid readers' understanding of chemometrics strategies for advanced data interpretation

WNT-DEPENDENT REGENERATIVE FUNCTION IS INDUCED IN LEUKEMIA-INITIATING AC133BRIGHT CELLS

The Cancer Stem Cell model supported the notion that leukemia was initiated and maintained in vivo by a small fraction of leukemia-initiating cells (LICs). Previous studies have suggested the involvement of Wnt signaling pathway in Acute Myeloid Leukemia (AML) by the ability to sustain the development of LICs. A novel hematopoietic stem and progenitor cell marker, monoclonal antibody AC133, recognizes the CD34bright CD38- subset of human acute myeloid leukemia cells, suggesting that it may be an early marker for the LICs. During the first part of my phD program we previously evaluated the ability of leukemic AC133+ fraction, to perform engraftment following to xenotransplantation in immunodeficient mouse model Rag2-/-\u3b3c-/-. The results showed that the surface marker AC133 is able to enrich for the cell fraction that contains the LICs. In consideration of our previously reported data, derived from the expression profiling analysis performed in normal (n=10) and leukemic (n=33) human long-term reconstituting AC133+ cells, we revealed that the ligand-dependent Wnt signaling is induced in AML through a diffuse expression and release of WNT10B, a hematopoietic stem cells regenerative-associated molecule. In situ detection performed on bone marrow biopsies of AML patients, showed the activation of the Wnt pathway, through the concomitant presence of the ligand WNT10B and of the active dephosphorylated \u3b2-catenin form, suggesting an autocrine / paracrine-type ligand-dependent activation mechanism. In consideration of the link between hematopoietic regeneration and developmental signaling, we transplanted primary AC133+ AML A46 cells into developing zebrafish. This biosensor model revealed the formation of ectopic structures by activation of dorsal organizer markers that act downstream of the Wnt pathway. These results suggested that the misappropriating Wnt associated functions can promote pathological stem cell-like regeneration responsiveness. The analyses performed in situ retained information on the cellular localization, enabling determination of the activity status of individual cells and allowing the tumor environment view. Taking this issue into consideration, during the second part of my phD program, I set up the application of a new in situ method for localized detection and genotyping of individual transcripts directly in cells and tissues. The mRNA in situ detection technique is based on padlock probes ligation and target priming rolling circle amplification allowing the single nucleotide resolution in heterogenous tissues. The mRNA in situ detection performed on bone marrow biopsies derived from AML patients, showed a diffuse localization pattern of WNT10B molecule in the tissue. Conversely, only the AC133bright cell population shows the Wnt signaling activation signature represented by the cytoplasmatic accumulation and nuclear translocation of the active form of \u3b2-catenin. In spite of this, we previously evidenced that the regenerative function of WNT signaling pathway is defined by the up-regulation of WNT10B, WNT10A, WNT2B and WNT6 loci, we identified the WNT10B as a major locus associated with the regenerative function and over-expressed by all AML patients. By the molecular evaluation of the WNT10B transcript, we isolated an aberrant splicing variant (WNT10BIVS1), that identify Non Core-Binding Factor Leukemia (NCBFL) class and whose potential role is discussed. Moreover, we demonstrate that the function of "leukemia stem cell", present in the cell population enriched for the marker AC133bright, is strictly related to regenerative function associated with WNT signaling, defining the key role of WNT10B ligand as a specific molecular marker for leuchemogenesis. This thesis defines the new suitable approaches to characterize the leukemia-initiating cells (LICs) and suggest the role of WNT10B as a new suitable target for AML

A Methodology to Develop Computer Vision Systems in Civil Engineering: Applications in Material Testing and Fish Tracking

[Resumen] La Visión Artificial proporciona una nueva y prometedora aproximación al campo de la Ingeniería Civil, donde es extremadamente importante medir con precisión diferentes procesos. Sin embargo, la Visión Artificial es un campo muy amplio que abarca multitud de técnicas y objetivos, y definir una aproximación de desarrollo sistemática es problemático. En esta tesis se propone una nueva metodología para desarrollar estos sistemas considerando las características y requisitos de la Ingeniería Civil. Siguiendo esta metodología se han desarrollado dos sistemas: Un sistema para la medición de desplazamientos y deformaciones en imágenes de ensayos de resistencia de materiales. Solucionando las limitaciones de los actuales sensores físicos que interfieren con el ensayo y solo proporcionan mediciones en un punto y una dirección determinada. Un sistema para la medición de la trayectoria de peces en escalas de hendidura vertical, con el que se pretende solucionar las carencias en el diseño de escalas obteniendo información sobre el comportamiento de los peces. Estas aplicaciones representan contribuciones significativas en el área, y demuestran que la metodología definida e implementada proporciona un marco de trabajo sistemático y confiable para el desarrollo de sistemas de Visión Artificial en Ingeniería Civil.[Resumo] A Visión Artificial proporciona unha nova e prometedora aproximación ó campo da Enxeñería Civil, onde é extremadamente importante medir con precisión diferentes procesos. Sen embargo, a Visión Artificial é un campo moi amplo que abarca multitude de técnicas e obxectivos, e definir unha aproximación de desenvolvemento sistemática é problemático. En esta tese proponse unha nova metodoloxía para desenvolver estes sistemas considerando as características e requisitos da Enxeñería Civil. Seguindo esta metodoloxía desenvolvéronse dous sistemas: Un sistema para a medición de desprazamentos e deformacións en imaxes de ensaios de resistencia de materiais. Solucionando as limitacións dos actuais sensores físicos que interfiren co ensaio e só proporcionan medicións nun punto e nunha dirección determinada. Un sistema para a medición da traxectoria de peixes en escalas de fenda vertical, co que se pretende solucionar as carencias no deseño de escalas obtendo información sobre o comportamento dos peixes. Estas aplicacións representan contribucións significativas na área, e demostran que a metodoloxía definida e implementada proporciona un marco de traballo sistemático e confiable para o desenvolvemento de sistemas de Visión Artificial en Enxeñería Civil.[Abstract] Computer Vision provides a new and promising approach to Civil Engineering, where it is extremely important to measure with accuracy real world processes. However, Computer Vision is a broad field, involving several techniques and topics, and the task of defining a systematic development approach is problematic. In this thesis a new methodology is carried out to develop these systems attending to the special characteristics and requirements of Civil Engineering. Following this methodology, two systems were developed: A system to measure displacements from real images of material surfaces taken during strength tests. This technique solves the limitation of current physical sensors, which interfere with the assay and which are limited to obtaining measurements in a single point of the material and in a single direction of the movement. A system to measure the trajectory of fishes in vertical slot fishways, whose purpose is to solve current lacks in the design of fishways by providing information of fish behavior. These applications represent significant contributions to the field and show that the defined and implemented methodology provides a systematic and reliable framework to develop a Computer Vision system in Civil Engineering

Characterising pattern asymmetry in pigmented skin lesions

Abstract. In clinical diagnosis of pigmented skin lesions asymmetric pigmentation is often indicative of melanoma. This paper describes a method and measures for characterizing lesion symmetry. The estimate of mirror symmetry is computed first for a number of axes at different degrees of rotation with respect to the lesion centre. The statistics of these estimates are the used to assess the overall symmetry. The method is applied to three different lesion representations showing the overall pigmentation, the pigmentation pattern, and the pattern of dermal melanin. The best measure is a 100% sensitive and 96% specific indicator of melanoma on a test set of 33 lesions, with a separate training set consisting of 66 lesions

Development and application of an antibody-based protein microarray to assess stress in grizzly bears (Ursus arctos)

There is an inherent conflict over land use between humans and wildlife. Human activities can alter habitat, creating pressure on North American large carnivore populations. Traditional wildlife techniques can be slow to show population declines, especially in long lived species with slow reproduction rates and high mortality of young, such as grizzly bears (Ursus arctos), which leads to delayed information for land managers trying to find the balance between human use of land and preservation of wildlife. Concern about population health of grizzlies in Western Alberta, Canada has lead to investigation of the impacts of current land use within grizzly bear habitat. The objective of this work was to develop a protein microarray that could detect patterns of physiological stress in a rapid manner with small samples of grizzly bear tissue. Sampling from four regions in the foothills of the Rocky Mountains in Alberta resulted in the capture of 133 bears. During the developmental phase, proteins involved with mitochondrial function were found, using two dimensional gel electrophoresis, to be altered in situations of increased stress. Limited cross-reactivity was found when evaluating grizzly bear stress protein expression using commercially available protein microarrays. The protein microarray developed in this thesis consists of 31commercial antibodies validated for grizzly bears. These antibodies recognize proteins associated with different aspects of the stress response, including the hypothalamic-pituitary-adrenal axis, apoptosis/cell cycle, cellular stress, and oxidative stress and inflammation. Skin was selected as the tissue for evaluation of protein expression. Strong correlations were found between many of the proteins within functional categories. Model selection for the protein categories revealed variation that corresponded with region, serum markers of stress (total cortisol and hsp60), growth, the density of roads in the habitat and the amount of anthropogenic change in the bear’s home range. Regional trends of expression found bears in Swan Hills and bears from North highway 16 having elevated expression of the proteins measured by the microarray. The protein microarray was thus able to detect expression patterns reflecting physiological and environmental markers. The array shows great promise for future use in detection of potential distress in wildlife populations due to alterations of their habitat

Multi-scale approaches for the statistical analysis of microarray data (with an application to 3D vesicle tracking)

The recent developments in experimental methods for gene data analysis, called microarrays, provide the possibility of interrogating changes in the expression of a vast number of genes in cell or tissue cultures and thus in depth exploration of disease conditions. As part of an ongoing program of research in Guy A. Rutter (G.A.R.) laboratory, Department of Biochemistry, University of Bristol, UK, with support from the Welcome Trust, we study the impact of established and of potentially new methods to the statistical analysis of gene expression data.EThOS - Electronic Theses Online ServiceGBUnited Kingdo