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.

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.

Statistical analysis and meta-analysis of microarray data

The microarray technology provides a high-throughput technique to study gene expression. Microarrays can help us diagnose different types of cancers, understand biological processes, assess host responses to drugs and pathogens, find markers for specific diseases, and much more. Microarray experiments generate large amounts of data. Thus, effective data processing and analysis are critical for making reliable inferences from the data. ^ The first part of dissertation addresses the problem of finding an optimal set of genes (biomarkers) to classify a set of samples as diseased or normal. Three statistical gene selection methods (GS, GS-NR, and GS-PCA) were developed to identify a set of genes that best differentiate between samples. A comparative study on different classification tools was performed and the best combinations of gene selection and classifiers for multi-class cancer classification were identified. For most of the benchmarking cancer data sets, the gene selection method proposed in this dissertation, GS, outperformed other gene selection methods. The classifiers based on Random Forests, neural network ensembles, and K-nearest neighbor (KNN) showed consistently god performance. A striking commonality among these classifiers is that they all use a committee-based approach, suggesting that ensemble classification methods are superior. ^ The same biological problem may be studied at different research labs and/or performed using different lab protocols or samples. In such situations, it is important to combine results from these efforts. The second part of the dissertation addresses the problem of pooling the results from different independent experiments to obtain improved results. Four statistical pooling techniques (Fisher inverse chi-square method, Logit method. Stouffer's Z transform method, and Liptak-Stouffer weighted Z-method) were investigated in this dissertation. These pooling techniques were applied to the problem of identifying cell cycle-regulated genes in two different yeast species. As a result, improved sets of cell cycle-regulated genes were identified. The last part of dissertation explores the effectiveness of wavelet data transforms for the task of clustering. Discrete wavelet transforms, with an appropriate choice of wavelet bases, were shown to be effective in producing clusters that were biologically more meaningful. ^

Improving novice analyst performance in modeling the sequence diagram in systems analysis: A cognitive complexity approach

The Unified Modeling Language (UML) has quickly become the industry standard for object-oriented software development. It is being widely used in organizations and institutions around the world. However, UML is often found to be too complex for novice systems analysts. Although prior research has identified difficulties novice analysts encounter in learning UML, no viable solution has been proposed to address these difficulties. Sequence-diagram modeling, in particular, has largely been overlooked. The sequence diagram models the behavioral aspects of an object-oriented software system in terms of interactions among its building blocks, i.e. objects and classes. It is one of the most commonly-used UML diagrams in practice. However, there has been little research on sequence-diagram modeling. The current literature scarcely provides effective guidelines for developing a sequence diagram. Such guidelines will be greatly beneficial to novice analysts who, unlike experienced systems analysts, do not possess relevant prior experience to easily learn how to develop a sequence diagram. There is the need for an effective sequence-diagram modeling technique for novices. This dissertation reports a research study that identified novice difficulties in modeling a sequence diagram and proposed a technique called CHOP (CHunking, Ordering, Patterning), which was designed to reduce the cognitive load by addressing the cognitive complexity of sequence-diagram modeling. The CHOP technique was evaluated in a controlled experiment against a technique recommended in a well-known textbook, which was found to be representative of approaches provided in many textbooks as well as practitioner literatures. The results indicated that novice analysts were able to perform better using the CHOP technique. This outcome seems have been enabled by pattern-based heuristics provided by the technique. Meanwhile, novice analysts rated the CHOP technique more useful although not significantly easier to use than the control technique. The study established that the CHOP technique is an effective sequence-diagram modeling technique for novice analysts.

Improving Novice Analyst Performance in Modeling the Sequence Diagram in Systems Analysis: A Cognitive Complexity Approach

The Unified Modeling Language (UML) has quickly become the industry standard for object-oriented software development. It is being widely used in organizations and institutions around the world. However, UML is often found to be too complex for novice systems analysts. Although prior research has identified difficulties novice analysts encounter in learning UML, no viable solution has been proposed to address these difficulties. Sequence-diagram modeling, in particular, has largely been overlooked. The sequence diagram models the behavioral aspects of an object-oriented software system in terms of interactions among its building blocks, i.e. objects and classes. It is one of the most commonly-used UML diagrams in practice. However, there has been little research on sequence-diagram modeling. The current literature scarcely provides effective guidelines for developing a sequence diagram. Such guidelines will be greatly beneficial to novice analysts who, unlike experienced systems analysts, do not possess relevant prior experience to easily learn how to develop a sequence diagram. There is the need for an effective sequence-diagram modeling technique for novices. This dissertation reports a research study that identified novice difficulties in modeling a sequence diagram and proposed a technique called CHOP (CHunking, Ordering, Patterning), which was designed to reduce the cognitive load by addressing the cognitive complexity of sequence-diagram modeling. The CHOP technique was evaluated in a controlled experiment against a technique recommended in a well-known textbook, which was found to be representative of approaches provided in many textbooks as well as practitioner literatures. The results indicated that novice analysts were able to perform better using the CHOP technique. This outcome seems have been enabled by pattern-based heuristics provided by the technique. Meanwhile, novice analysts rated the CHOP technique more useful although not significantly easier to use than the control technique. The study established that the CHOP technique is an effective sequence-diagram modeling technique for novice analysts.

Quantitative Analysis and Determination of Microcystin in water by Capillary Electrophoresis Mass Spectrometry

The presence of harmful algal blooms (HAB) is a growing concern in aquatic environments. Among HAB organisms, cyanobacteria are of special concern because they have been reported worldwide to cause environmental and human health problem through contamination of drinking water. Although several analytical approaches have been applied to monitoring cyanobacteria toxins, conventional methods are costly and time-consuming so that analyses take weeks for field sampling and subsequent lab analysis. Capillary electrophoresis (CE) becomes a particularly suitable analytical separation method that can couple very small samples and rapid separations to a wide range of selective and sensitive detection techniques. This paper demonstrates a method for rapid separation and identification of four microcystin variants commonly found in aquatic environments. CE coupled to UV and electrospray ionization time-of-flight mass spectrometry (ESI-TOF) procedures were developed. All four analytes were separated within 6 minutes. The ESI-TOF experiment provides accurate molecular information, which further identifies analytes.