Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors.

Network construction and graph theoretical analysis of functional language networks in pediatric epilepsy

This dissertation introduces a new approach for assessing the effects of pediatric epilepsy on the language connectome. Two novel data-driven network construction approaches are presented. These methods rely on connecting different brain regions using either extent or intensity of language related activations as identified by independent component analysis of fMRI data. An auditory description decision task (ADDT) paradigm was used to activate the language network for 29 patients and 30 controls recruited from three major pediatric hospitals. Empirical evaluations illustrated that pediatric epilepsy can cause, or is associated with, a network efficiency reduction. Patients showed a propensity to inefficiently employ the whole brain network to perform the ADDT language task; on the contrary, controls seemed to efficiently use smaller segregated network components to achieve the same task. To explain the causes of the decreased efficiency, graph theoretical analysis was carried out. The analysis revealed no substantial global network feature differences between the patient and control groups. It also showed that for both subject groups the language network exhibited small-world characteristics; however, the patient's extent of activation network showed a tendency towards more random networks. It was also shown that the intensity of activation network displayed ipsilateral hub reorganization on the local level. The left hemispheric hubs displayed greater centrality values for patients, whereas the right hemispheric hubs displayed greater centrality values for controls. This hub hemispheric disparity was not correlated with a right atypical language laterality found in six patients. Finally it was shown that a multi-level unsupervised clustering scheme based on self-organizing maps, a type of artificial neural network, and k-means was able to fairly and blindly separate the subjects into their respective patient or control groups. The clustering was initiated using the local nodal centrality measurements only. Compared to the extent of activation network, the intensity of activation network clustering demonstrated better precision. This outcome supports the assertion that the local centrality differences presented by the intensity of activation network can be associated with focal epilepsy.^

Analysis of fractured terrain using remote sensing and geographic information systems : establishing a correlation between fracture network properties and vegetation

This research analyzed the spatial relationship between a mega-scale fracture network and the occurrence of vegetation in an arid region. High-resolution aerial photographs of Arches National Park, Utah were used for digital image processing. Four sets of large-scale joints were digitized from the rectified color photograph in order to characterize the geospatial properties of the fracture network with the aid of a Geographic Information System. An unsupervised landcover classification was carried out to identify the spatial distribution of vegetation on the fractured outcrop. Results of this study confirm that the WNW-ESE alignment of vegetation is dominantly controlled by the spatial distribution of the systematic joint set, which in turn parallels the regional fold axis. This research provides insight into the spatial heterogeneity inherent to fracture networks, as well as the effects of jointing on the distribution of surface vegetation in desert environments.

A Static Traffic Assignment Model Combined with an Artificial Neural Network Delay Model

As traffic congestion continues to worsen in large urban areas, solutions are urgently sought. However, transportation planning models, which estimate traffic volumes on transportation network links, are often unable to realistically consider travel time delays at intersections. Introducing signal controls in models often result in significant and unstable changes in network attributes, which, in turn, leads to instability of models. Ignoring the effect of delays at intersections makes the model output inaccurate and unable to predict travel time. To represent traffic conditions in a network more accurately, planning models should be capable of arriving at a network solution based on travel costs that are consistent with the intersection delays due to signal controls. This research attempts to achieve this goal by optimizing signal controls and estimating intersection delays accordingly, which are then used in traffic assignment. Simultaneous optimization of traffic routing and signal controls has not been accomplished in real-world applications of traffic assignment. To this end, a delay model dealing with five major types of intersections has been developed using artificial neural networks (ANNs). An ANN architecture consists of interconnecting artificial neurons. The architecture may either be used to gain an understanding of biological neural networks, or for solving artificial intelligence problems without necessarily creating a model of a real biological system. The ANN delay model has been trained using extensive simulations based on TRANSYT-7F signal optimizations. The delay estimates by the ANN delay model have percentage root-mean-squared errors (%RMSE) that are less than 25.6%, which is satisfactory for planning purposes. Larger prediction errors are typically associated with severely oversaturated conditions. A combined system has also been developed that includes the artificial neural network (ANN) delay estimating model and a user-equilibrium (UE) traffic assignment model. The combined system employs the Frank-Wolfe method to achieve a convergent solution. Because the ANN delay model provides no derivatives of the delay function, a Mesh Adaptive Direct Search (MADS) method is applied to assist in and expedite the iterative process of the Frank-Wolfe method. The performance of the combined system confirms that the convergence of the solution is achieved, although the global optimum may not be guaranteed.

Principal Component Analysis and Assessment of Language Network Activation Patterns in Pediatric Epilepsy

This dissertation establishes a novel data-driven method to identify language network activation patterns in pediatric epilepsy through the use of the Principal Component Analysis (PCA) on functional magnetic resonance imaging (fMRI). A total of 122 subjects’ data sets from five different hospitals were included in the study through a web-based repository site designed here at FIU. Research was conducted to evaluate different classification and clustering techniques in identifying hidden activation patterns and their associations with meaningful clinical variables. The results were assessed through agreement analysis with the conventional methods of lateralization index (LI) and visual rating. What is unique in this approach is the new mechanism designed for projecting language network patterns in the PCA-based decisional space. Synthetic activation maps were randomly generated from real data sets to uniquely establish nonlinear decision functions (NDF) which are then used to classify any new fMRI activation map into typical or atypical. The best nonlinear classifier was obtained on a 4D space with a complexity (nonlinearity) degree of 7. Based on the significant association of language dominance and intensities with the top eigenvectors of the PCA decisional space, a new algorithm was deployed to delineate primary cluster members without intensity normalization. In this case, three distinct activations patterns (groups) were identified (averaged kappa with rating 0.65, with LI 0.76) and were characterized by the regions of: 1) the left inferior frontal Gyrus (IFG) and left superior temporal gyrus (STG), considered typical for the language task; 2) the IFG, left mesial frontal lobe, right cerebellum regions, representing a variant left dominant pattern by higher activation; and 3) the right homologues of the first pattern in Broca's and Wernicke's language areas. Interestingly, group 2 was found to reflect a different language compensation mechanism than reorganization. Its high intensity activation suggests a possible remote effect on the right hemisphere focus on traditionally left-lateralized functions. In retrospect, this data-driven method provides new insights into mechanisms for brain compensation/reorganization and neural plasticity in pediatric epilepsy.

Analysis and comparison of network performance with different network parameters

The purpose of this study was to analyze the network performance by observing the effect of varying network size and data link rate on one of the most commonly found network configurations. Computer networks have been growing explosively. Networking is used in every aspect of business, including advertising, production, shipping, planning, billing, and accounting. Communication takes place through networks that form the basis of transfer of information. The number and type of components may vary from network to network depending on several factors such as requirement and actual physical placement of the networks. There is no fixed size of the networks and they can be very small consisting of say five to six nodes or very large consisting of over two thousand nodes. The varying network sizes make it very important to study the network performance so as to be able to predict the functioning and the suitability of the network. The findings demonstrated that the network performance parameters such as global delay, load, router processor utilization, router processor delay, etc. are affected. The findings demonstrated that the network performance parameters such as global delay, load, router processor utilization, router processor delay, etc. are affected significantly due to the increase in the size of the network and that there exists a correlation between the various parameters and the size of the network. These variations are not only dependent on the magnitude of the change in the actual physical area of the network but also on the data link rate used to connect the various components of the network.

Network Construction and Graph Theoretical Analysis of Functional Language Networks in Pediatric Epilepsy

This dissertation introduces a new approach for assessing the effects of pediatric epilepsy on the language connectome. Two novel data-driven network construction approaches are presented. These methods rely on connecting different brain regions using either extent or intensity of language related activations as identified by independent component analysis of fMRI data. An auditory description decision task (ADDT) paradigm was used to activate the language network for 29 patients and 30 controls recruited from three major pediatric hospitals. Empirical evaluations illustrated that pediatric epilepsy can cause, or is associated with, a network efficiency reduction. Patients showed a propensity to inefficiently employ the whole brain network to perform the ADDT language task; on the contrary, controls seemed to efficiently use smaller segregated network components to achieve the same task. To explain the causes of the decreased efficiency, graph theoretical analysis was carried out. The analysis revealed no substantial global network feature differences between the patient and control groups. It also showed that for both subject groups the language network exhibited small-world characteristics; however, the patient’s extent of activation network showed a tendency towards more random networks. It was also shown that the intensity of activation network displayed ipsilateral hub reorganization on the local level. The left hemispheric hubs displayed greater centrality values for patients, whereas the right hemispheric hubs displayed greater centrality values for controls. This hub hemispheric disparity was not correlated with a right atypical language laterality found in six patients. Finally it was shown that a multi-level unsupervised clustering scheme based on self-organizing maps, a type of artificial neural network, and k-means was able to fairly and blindly separate the subjects into their respective patient or control groups. The clustering was initiated using the local nodal centrality measurements only. Compared to the extent of activation network, the intensity of activation network clustering demonstrated better precision. This outcome supports the assertion that the local centrality differences presented by the intensity of activation network can be associated with focal epilepsy.