A Cloud-Edge-aided Incremental High-order Possibilistic c-Means Algorithm for Medical Data Clustering

Medical Internet of Things are generating a big volume of data to enable smart medicine that tries to offer computer-aided medical and healthcare services with artificial intelligence techniques like deep learning and clustering. However, it is a challenging issue for deep learning and clustering algorithms to analyze large medical data because of their high computational complexity, thus hindering the progress of smart medicine. In this paper, we present an incremental high-order possibilistic c-means algorithm on a cloud-edge computing system to achieve medical data co-clustering of multiple hospitals in different locations. Specifically, each hospital employs the deep computation model to learn a feature tensor of each medical data object on the local edge computing system and then uploads the feature tensors to the cloud computing platform. The high-order possibilistic c-means algorithm (HoPCM) is performed on the cloud system for medical data clustering on uploaded feature tensors. Once the new medical data feature tensors are arriving at the cloud computing platform, the incremental high-order possibilistic c-means algorithm (IHoPCM) is performed on the combination of the new feature tensors and the previous clustering centers to obtain clustering results for the feature tensors received to date. In this way, repeated clustering on the previous feature tensors is avoided to improve the clustering efficiency. In the experiments, we compare different algorithms on two medical datasets regarding clustering accuracy and clustering efficiency. Results show that the presented IHoPCM method achieves great improvements over the compared algorithms in clustering accuracy and efficiency

Biomedical applications of belief networks

Biomedicine is an area in which computers have long been expected to play a significant role. Although many of the early claims have proved unrealistic, computers are gradually becoming accepted in the biomedical, clinical and research environment. Within these application areas, expert systems appear to have met with the most resistance, especially when applied to image interpretation.In order to improve the acceptance of computerised decision support systems it is necessary to provide the information needed to make rational judgements concerning the inferences the system has made. This entails an explanation of what inferences were made, how the inferences were made and how the results of the inference are to be interpreted. Furthermore there must be a consistent approach to the combining of information from low level computational processes through to high level expert analyses.nformation from low level computational processes through to high level expert analyses. Until recently ad hoc formalisms were seen as the only tractable approach to reasoning under uncertainty. A review of some of these formalisms suggests that they are less than ideal for the purposes of decision making. Belief networks provide a tractable way of utilising probability theory as an inference formalism by combining the theoretical consistency of probability for inference and decision making, with the ability to use the knowledge of domain experts.nowledge of domain experts. The potential of belief networks in biomedical applications has already been recog¬ nised and there has been substantial research into the use of belief networks for medical diagnosis and methods for handling large, interconnected networks. In this thesis the use of belief networks is extended to include detailed image model matching to show how, in principle, feature measurement can be undertaken in a fully probabilistic way. The belief networks employed are usually cyclic and have strong influences between adjacent nodes, so new techniques for probabilistic updating based on a model of the matching process have been developed.An object-orientated inference shell called FLAPNet has been implemented and used to apply the belief network formalism to two application domains. The first application is model-based matching in fetal ultrasound images. The imaging modality and biological variation in the subject make model matching a highly uncertain process. A dynamic, deformable model, similar to active contour models, is used. A belief network combines constraints derived from local evidence in the image, with global constraints derived from trained models, to control the iterative refinement of an initial model cue.In the second application a belief network is used for the incremental aggregation of evidence occurring during the classification of objects on a cervical smear slide as part of an automated pre-screening system. A belief network provides both an explicit domain model and a mechanism for the incremental aggregation of evidence, two attributes important in pre-screening systems.Overall it is argued that belief networks combine the necessary quantitative features required of a decision support system with desirable qualitative features that will lead to improved acceptability of expert systems in the biomedical domain

Investigation of cytotoxic properties of some heterocyclic derivatives by molecular modeling approaches

Currently, many technologies have been adopted to boost the efficiency of drug development and overcome obstacles in the drug discovery pipeline. The application of these approaches spans a wide range, from bioactivity predictions, de novo compound synthesis, target identification to hit discovery, and lead optimization. This dissertation comprises two studies. First, we proposed an original approach based on statistical consideration dedicated to k-means clustering analysis in order to define a set of rules for structural features that would help in designing novel anti-cancer drug candidates. It has been applied successfully to classify 500 cytotoxic compounds with 21 molecular descriptors into distinct clusters. The percentage of molecules in each cluster is 50%, 24.88%, and 25.12% for cluster 1, cluster 2, and cluster 3, respectively. Each cluster groups a homogeneous class of molecules with respect to their molecular descriptors. Silhouette analysis, used as a cluster validation approch proves that the molecules are very well clustered, and there are no molecules placed in the wrong cluster. In silico screening of pharmacological properties ADME and evaluation of drug-likeness were performed for all molecules. The quantitative analysis of molecular electrostatic potential was performed to identify the nucleophilic and electrophilic sites in the representative molecule of each cluster. In addition, a molecular docking study was carried out to investigate the interactions of the paragon molecules with the active binding sites of six different targets. Our findings provide a guide to assist the chemist in selecting and testing only the potential molecules with good pharmacokinetic profiles to improve the clinical outcomes of drug therapies. Second, a simulation-based investigation was conducted to examine the CHK1 inhibitory activity of cytotoxic xanthone derivatives using a hierarchical workflow for molecular docking, MD simulation, ADME-TOX prediction, and MEP analysis. A molecular docking study was conducted for the forty-three xanthone derivatives along with standard Prexasertib into the selected CHK1 protein structures 7AKM and 7AKO. Furthermore, MD studies support molecular docking results and validate the stability of studied complexes in physiological conditions. Moreover, in silico ADME-TOX studies are used to predict the pharmacokinetic, pharmacodynamic, and toxicological properties of the selected eight xanthones and the standard Prexasertib. The quantitative analysis of electrostatic potential was performed for the lead compound L36 to identify the reactive sites and possible non- covalent interactions. Our study provides new unexplored insights into xanthones as CHK1 inhibitors and identified L36 as a potential drug candidate that could undergo further in vivo assays and optimization, laying a solid foundation for the development of CHK1 inhibitors and cancer drug discovery. To the best of our knowledge, this is the first time such a study was conducted for the xanthones with CHK1 by using a computational based approach

Investigation of cytotoxic properties of some heterocyclic derivatives by molecular modeling

Currently, many technologies have been adopted to boost the efficiency of drugdevelopment and overcome obstacles in the drug discovery pipeline. The application of these approaches spans a wide range, from bioactivity predictions, de novo compound synthesis, target identification to hit discovery, and lead optimization. This dissertation comprises two studies. First, we proposed an original approach based on statistical consideration dedicated to k-means clustering analysis in order to define a set of rules for structural features that would help in designing novel anti-cancer drug candidates. It has been applied successfully to classify 500 cytotoxic compounds with 21 molecular descriptors into distinct clusters. The percentage of molecules in each cluster is 50%, 24.88%, and 25.12% for cluster 1, cluster 2, and cluster 3, respectively. Each cluster groups a homogeneous class of molecules with respect to their molecular descriptors. Silhouette analysis, used as a cluster validation approach proves that the molecules are very well clustered, and there are no molecules placed in the wrong cluster. In silico screening of pharmacological properties ADME and evaluation of drug-likeness were performed for all molecules. The quantitative analysis of molecular electrostatic potential was performed to identify the nucleophilic and electrophilic sites in the representative molecule of each cluster. In addition, a molecular docking study was carried out to investigate the interactions of the paragon molecules with the active binding sites of six different targets. Our findings provide a guide to assist the chemist in selecting and testing only the potential molecules with good pharmacokinetic profiles to improve the clinical outcomes of drug therapies. Second, a simulation-based investigation was conducted to examine the CHK1 inhibitory activity of cytotoxic xanthone derivatives using a hierarchical workflow for molecular docking, MD simulation, ADME-TOX prediction, and MEP analysis. A molecular docking study was conducted for the forty-three xanthone derivatives along with standard Prexasertib into the selected CHK1 protein structures 7AKM and 7AKO. Furthermore, MD studies support molecular docking results and validate the stability of studied complexes in physiological conditions. Moreover, in silico ADME-TOX studies are used to predict the pharmacokinetic, pharmacodynamic, and toxicological properties of the selected eight xanthones and the standard Prexasertib. The quantitative analysis of electrostatic potential was performed for the lead compound L36 to identify the reactive sites and possible noncovalent interactions. Our study provides new unexplored insights into xanthones as CHK1 inhibitors and identified L36 as a potential drug candidate that could undergo further in vivo assays and optimization, laying a solid foundation for the development of CHK1 inhibitors and cancer drug discovery. To the best of our knowledge, this is the first time such a study was conducted for the xanthones with CHK1 by using a computational based approach

An intelligent decision support system for acute lymphoblastic leukaemia detection

The morphological analysis of blood smear slides by haematologists or haematopathologists is one of the diagnostic procedures available to evaluate the presence of acute leukaemia. This operation is a complex and costly process, and often lacks standardized accuracy owing to a variety of factors, including insufficient expertise and operator fatigue. This research proposes an intelligent decision support system for automatic detection of acute lymphoblastic leukaemia (ALL) using microscopic blood smear images to overcome the above barrier. The work has four main key stages. (1) Firstly, a modified marker-controlled watershed algorithm integrated with the morphological operations is proposed for the segmentation of the membrane of the lymphocyte and lymphoblast cell images. The aim of this stage is to isolate a lymphocyte/lymphoblast cell membrane from touching and overlapping of red blood cells, platelets and artefacts of the microscopic peripheral blood smear sub-images. (2) Secondly, a novel clustering algorithm with stimulating discriminant measure (SDM) of both within- and between-cluster scatter variances is proposed to produce robust segmentation of the nucleus and cytoplasm of lymphocytic cell membranes. The SDM measures are used in conjunction with Genetic Algorithm for the clustering of nucleus, cytoplasm, and background regions. (3) Thirdly, a total of eighty features consisting of shape, texture, and colour information from the nucleus and cytoplasm of the identified lymphocyte/lymphoblast images are extracted. (4) Finally, the proposed feature optimisation algorithm, namely a variant of Bare-Bones Particle Swarm Optimisation (BBPSO), is presented to identify the most significant discriminative characteristics of the nucleus and cytoplasm segmented by the SDM-based clustering algorithm. The proposed BBPSO variant algorithm incorporates Cuckoo Search, Dragonfly Algorithm, BBPSO, and local and global random walk operations of uniform combination, and Lévy flights to diversify the search and mitigate the premature convergence problem of the conventional BBPSO. In addition, it also employs subswarm concepts, self-adaptive parameters, and convergence degree monitoring mechanisms to enable fast convergence. The optimal feature subsets identified by the proposed algorithm are subsequently used for ALL detection and classification. The proposed system achieves the highest classification accuracy of 96.04% and significantly outperforms related meta-heuristic search methods and related research for ALL detection

Medical image segmentation using edge-based active contours.

The main purpose of image segmentation using active contours is to extract the object of interest in images based on textural or boundary information. Active contour methods have been widely used in image segmentation applications due to their good boundary detection accuracy. In the context of medical image segmentation, weak edges and inhomogeneities remain important issues that may limit the accuracy of any segmentation method formulated using active contour models. This thesis develops new methods for segmentation of medical images based on the active contour models. Three different approaches are pursued: The first chapter proposes a novel external force that integrates gradient vector flow (GVF) field forces and balloon forces based on a weighting factor computed according to local image features. The proposed external force reduces noise sensitivity, improves performance over weak edges and allows initialization with a single manually selected point. The next chapter proposes a level set method that is based on the minimization of an objective energy functional whose energy terms are weighted according to their relative importance in detecting boundaries. This relative importance is computed based on local edge features collected from the adjacent region inside and outside of the evolving contour. The local edge features employed are the edge intensity and the degree of alignment between the images gradient vector flow field and the evolving contours normal. Finally, chapter 5 presents a framework that is capable of segmenting the cytoplasm of each individual cell and can address the problem of segmenting overlapping cervical cells using edge-based active contours. The main goal of our methodology is to provide significantly fully segmented cells with high accuracy segmentation results. All of the proposed methods are then evaluated for segmentation of various regions in real MRI and CT slices, X-ray images and cervical cell images. Evaluation results show that the proposed method leads to more accurate boundary detection results than other edge-based active contour methods (snake and level-set), particularly around weak edges

Hematological image analysis for acute lymphoblastic leukemia detection and classification

Microscopic analysis of peripheral blood smear is a critical step in detection of leukemia.However, this type of light microscopic assessment is time consuming, inherently subjective, and is governed by hematopathologists clinical acumen and experience. To circumvent such problems, an efficient computer aided methodology for quantitative analysis of peripheral blood samples is required to be developed. In this thesis, efforts are therefore made to devise methodologies for automated detection and subclassification of Acute Lymphoblastic Leukemia (ALL) using image processing and machine learning methods.Choice of appropriate segmentation scheme plays a vital role in the automated disease recognition process. Accordingly to segment the normal mature lymphocyte and malignant lymphoblast images into constituent morphological regions novel schemes have been proposed. In order to make the proposed schemes viable from a practical and real–time stand point, the segmentation problem is addressed in both supervised and unsupervised framework. These proposed methods are based on neural network,feature space clustering, and Markov random field modeling, where the segmentation problem is formulated as pixel classification, pixel clustering, and pixel labeling problem respectively. A comprehensive validation analysis is presented to evaluate the performance of four proposed lymphocyte image segmentation schemes against manual segmentation results provided by a panel of hematopathologists. It is observed that morphological components of normal and malignant lymphocytes differ significantly. To automatically recognize lymphoblasts and detect ALL in peripheral blood samples, an efficient methodology is proposed.Morphological, textural and color features are extracted from the segmented nucleus and cytoplasm regions of the lymphocyte images. An ensemble of classifiers represented as EOC3 comprising of three classifiers shows highest classification accuracy of 94.73% in comparison to individual members. The subclassification of ALL based on French–American–British (FAB) and World Health Organization (WHO) criteria is essential for prognosis and treatment planning. Accordingly two independent methodologies are proposed for automated classification of malignant lymphocyte (lymphoblast) images based on morphology and phenotype. These methods include lymphoblast image segmentation, nucleus and cytoplasm feature extraction, and efficient classification