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. ^

Bioinformatic analysis for exploring relationships between genes and gene products

To carry out their specific roles in the cell, genes and gene products often work together in groups, forming many relationships among themselves and with other molecules. Such relationships include physical protein-protein interaction relationships, regulatory relationships, metabolic relationships, genetic relationships, and much more. With advances in science and technology, some high throughput technologies have been developed to simultaneously detect tens of thousands of pairwise protein-protein interactions and protein-DNA interactions. However, the data generated by high throughput methods are prone to noise. Furthermore, the technology itself has its limitations, and cannot detect all kinds of relationships between genes and their products. Thus there is a pressing need to investigate all kinds of relationships and their roles in a living system using bioinformatic approaches, and is a central challenge in Computational Biology and Systems Biology. This dissertation focuses on exploring relationships between genes and gene products using bioinformatic approaches. Specifically, we consider problems related to regulatory relationships, protein-protein interactions, and semantic relationships between genes. A regulatory element is an important pattern or "signal", often located in the promoter of a gene, which is used in the process of turning a gene "on" or "off". Predicting regulatory elements is a key step in exploring the regulatory relationships between genes and gene products. In this dissertation, we consider the problem of improving the prediction of regulatory elements by using comparative genomics data. With regard to protein-protein interactions, we have developed bioinformatics techniques to estimate support for the data on these interactions. While protein-protein interactions and regulatory relationships can be detected by high throughput biological techniques, there is another type of relationship called semantic relationship that cannot be detected by a single technique, but can be inferred using multiple sources of biological data. The contributions of this thesis involved the development and application of a set of bioinformatic approaches that address the challenges mentioned above. These included (i) an EM-based algorithm that improves the prediction of regulatory elements using comparative genomics data, (ii) an approach for estimating the support of protein-protein interaction data, with application to functional annotation of genes, (iii) a novel method for inferring functional network of genes, and (iv) techniques for clustering genes using multi-source data.

The applied computer science of economic analyses: Internet prioritization and Internet pricing, and software engineering and software pricing for the mass market

This research examines evolving issues in applied computer science and applies economic and business analyses as well. There are two main areas. The first is internetwork communications as embodied by the Internet. The goal of the research is to devise an efficient pricing, prioritization, and incentivization plan that could be realistically implemented on the existing infrastructure. Criteria include practical and economic efficiency, and proper incentives for both users and providers. Background information on the evolution and functional operation of the Internet is given, and relevant literature is surveyed and analyzed. Economic analysis is performed on the incentive implications of the current pricing structure and organization. The problems are identified, and minimally disruptive solutions are proposed for all levels of implementation to the lowest level protocol. Practical issues are considered and performance analyses are done. The second area of research is mass market software engineering, and how this differs from classical software engineering. Software life-cycle revenues are analyzed and software pricing and timing implications are derived. A profit maximizing methodology is developed to select or defer the development of software features for inclusion in a given release. An iterative model of the stages of the software development process is developed, taking into account new communications capabilities as well as profitability. ^

An innovative approach to teaching structural induction for computer science

Proofs by induction are central to many computer science areas such as data structures, theory of computation, programming languages, program efficiency-time complexity, and program correctness. Proofs by induction can also improve students’ understanding and performance of computer science concepts such as programming languages, algorithm design, and recursion, as well as serve as a medium for teaching them. Even though students are exposed to proofs by induction in many courses of their curricula, they still have difficulties understanding and performing them. This impacts the whole course of their studies, since proofs by induction are omnipresent in computer science. Specifically, students do not gain conceptual understanding of induction early in the curriculum and as a result, they have difficulties applying it to more advanced areas later on in their studies. The goal of my dissertation is twofold: (1) identifying sources of computer science students’ difficulties with proofs by induction, and (2) developing a new approach to teaching proofs by induction by way of an interactive and multimodal electronic book (e-book). For the first goal, I undertook a study to identify possible sources of computer science students’ difficulties with proofs by induction. Its results suggest that there is a close correlation between students’ understanding of inductive definitions and their understanding and performance of proofs by induction. For designing and developing my e-book, I took into consideration the results of my study, as well as the drawbacks of the current methodologies of teaching proofs by induction for computer science. I designed my e-book to be used as a standalone and complete educational environment. I also conducted a study on the effectiveness of my e-book in the classroom. The results of my study suggest that, unlike the current methodologies of teaching proofs by induction for computer science, my e-book helped students overcome many of their difficulties and gain conceptual understanding of proofs induction.

The impact of a Classroom Performance System on learning gains in a biology course for science majors

This study was conducted to determine if the use of the technology known as Classroom Performance System (CPS), specifically referred to as "Clickers", improves the learning gains of students enrolled in a biology course for science majors. CPS is one of a group of developing technologies adapted for providing feedback in the classroom using a learner-centered approach. It supports and facilitates discussion among students and between them and teachers, and provides for participation by passive students. Advocates, influenced by constructivist theories, claim increased academic achievement. In science teaching, the results have been mixed, but there is some evidence of improvements in conceptual understanding. The study employed a pretest-posttest, non-equivalent groups experimental design. The sample consisted of 226 participants in six sections of a college biology course at a large community college in South Florida with two instructors trained in the use of clickers. Each instructor randomly selected their sections into CPS (treatment) and non-CPS (control) groups. All participants filled out a survey that included demographic data at the beginning of the semester. The treatment group used clicker questions throughout, with discussions as necessary, whereas the control groups answered the same questions as quizzes, similarly engaging in discussion where necessary. The learning gains were assessed on a pre/post-test basis. The average learning gains, defined as the actual gain divided by the possible gain, were slightly better in the treatment group than in the control group, but the difference was statistically non-significant. An Analysis of Covariance (ANCOVA) statistic with pretest scores as the covariate was conducted to test for significant differences between the treatment and control groups on the posttest. A second ANCOVA was used to determine the significance of differences between the treatment and control groups on the posttest scores, after controlling for sex, GPA, academic status, experience with clickers, and instructional style. The results indicated a small increase in learning gains but these were not statistically significant. The data did not support an increase in learning based on the use of the CPS technology. This study adds to the body of research that questions whether CPS technology merits classroom adaptation.

Phylogenetic analysis of within -host serially-sampled viral data

The primary goal of this dissertation is the study of patterns of viral evolution inferred from serially-sampled sequence data, i.e., sequence data obtained from strains isolated at consecutive time points from a single patient or host. RNA viral populations have an extremely high genetic variability, largely due to their astronomical population sizes within host systems, high replication rate, and short generation time. It is this aspect of their evolution that demands special attention and a different approach when studying the evolutionary relationships of serially-sampled sequence data. New methods that analyze serially-sampled data were developed shortly after a groundbreaking HIV-1 study of several patients from which viruses were isolated at recurring intervals over a period of 10 or more years. These methods assume a tree-like evolutionary model, while many RNA viruses have the capacity to exchange genetic material with one another using a process called recombination. ^ A genealogy involving recombination is best described by a network structure. A more general approach was implemented in a new computational tool, Sliding MinPD, one that is mindful of the sampling times of the input sequences and that reconstructs the viral evolutionary relationships in the form of a network structure with implicit representations of recombination events. The underlying network organization reveals unique patterns of viral evolution and could help explain the emergence of disease-associated mutants and drug-resistant strains, with implications for patient prognosis and treatment strategies. In order to comprehensively test the developed methods and to carry out comparison studies with other methods, synthetic data sets are critical. Therefore, appropriate sequence generators were also developed to simulate the evolution of serially-sampled recombinant viruses, new and more through evaluation criteria for recombination detection methods were established, and three major comparison studies were performed. The newly developed tools were also applied to "real" HIV-1 sequence data and it was shown that the results represented within an evolutionary network structure can be interpreted in biologically meaningful ways. ^

An Innovative Approach to Teaching Structural Induction for Computer Science

Proofs by induction are central to many computer science areas such as data structures, theory of computation, programming languages, program efficiency-time complexity, and program correctness. Proofs by induction can also improve students’ understanding of and performance with computer science concepts such as programming languages, algorithm design, and recursion, as well as serve as a medium for teaching them. Even though students are exposed to proofs by induction in many courses of their curricula, they still have difficulties understanding and performing them. This impacts the whole course of their studies, since proofs by induction are omnipresent in computer science. Specifically, students do not gain conceptual understanding of induction early in the curriculum and as a result, they have difficulties applying it to more advanced areas later on in their studies. The goal of my dissertation is twofold: 1. identifying sources of computer science students’ difficulties with proofs by induction, and 2. developing a new approach to teaching proofs by induction by way of an interactive and multimodal electronic book (e-book). For the first goal, I undertook a study to identify possible sources of computer science students’ difficulties with proofs by induction. Its results suggest that there is a close correlation between students’ understanding of inductive definitions and their understanding and performance of proofs by induction. For designing and developing my e-book, I took into consideration the results of my study, as well as the drawbacks of the current methodologies of teaching proofs by induction for computer science. I designed my e-book to be used as a standalone and complete educational environment. I also conducted a study on the effectiveness of my e-book in the classroom. The results of my study suggest that, unlike the current methodologies of teaching proofs by induction for computer science, my e-book helped students overcome many of their difficulties and gain conceptual understanding of proofs induction.

The Impact of a Classroom Performance System on Learning Gains in a Biology Course for Science Majors

This study was conducted to determine if the use of the technology known as Classroom Performance System (CPS), specifically referred to as “Clickers”, improves the learning gains of students enrolled in a biology course for science majors. CPS is one of a group of developing technologies adapted for providing feedback in the classroom using a learner-centered approach. It supports and facilitates discussion among students and between them and teachers, and provides for participation by passive students. Advocates, influenced by constructivist theories, claim increased academic achievement. In science teaching, the results have been mixed, but there is some evidence of improvements in conceptual understanding. The study employed a pretest-posttest, non-equivalent groups experimental design. The sample consisted of 226 participants in six sections of a college biology course at a large community college in South Florida with two instructors trained in the use of clickers. Each instructor randomly selected their sections into CPS (treatment) and non-CPS (control) groups. All participants filled out a survey that included demographic data at the beginning of the semester. The treatment group used clicker questions throughout, with discussions as necessary, whereas the control groups answered the same questions as quizzes, similarly engaging in discussion where necessary. The learning gains were assessed on a pre/post-test basis. The average learning gains, defined as the actual gain divided by the possible gain, were slightly better in the treatment group than in the control group, but the difference was statistically non-significant. An Analysis of Covariance (ANCOVA) statistic with pretest scores as the covariate was conducted to test for significant differences between the treatment and control groups on the posttest. A second ANCOVA was used to determine the significance of differences between the treatment and control groups on the posttest scores, after controlling for sex, GPA, academic status, experience with clickers, and instructional style. The results indicated a small increase in learning gains but these were not statistically significant. The data did not support an increase in learning based on the use of the CPS technology. This study adds to the body of research that questions whether CPS technology merits classroom adaptation.

An evaluation of a curriculum response to the State of Florida mandate for computer literacy at a large comprehensive high school in Dade County, Florida

Minimum Student Performance Standards in Computer Literacy and Science were passed by the Florida Legislature through the Educational Reform Act of 1983. This act mandated that all Florida high school graduates receive training in computer literacy. Schools and school systems were charged with the task of determining the best methods to deliver this instruction to their students. The scope of this study is to evaluate one school's response to the state of Florida's computer literacy mandate. The study was conducted at Miami Palmetto Senior High School, located in Dade County, Florida. The administration of Miami Palmetto Senior High School chose to develop and implement a new program to comply with the state mandate - integrating computer literacy into the existing biology curriculum. The study evaluated the curriculum to determine if computer literacy could be integrated successfully and meet both the biology and computer literacy objectives. The findings in this study showed that there were no significant differences between biology scores of the students taking the integrated curriculum and those taking a traditional curriculum of biology. Student in the integrated curriculum not only met the biology objectives as well as those in the traditional curriculum, they also successfully completed the intended objectives for computer literacy. Two sets of objectives were successfully completed in the integrated classes in the same amount of time used to complete one set of objectives in the traditional biology classes. Therefore, integrated curriculum was the more efficient means of meeting the intended objectives of both biology and computer literacy.

Signal processing of physiological signals for automated assessment of stress in computer users

The need to provide computers with the ability to distinguish the affective state of their users is a major requirement for the practical implementation of affective computing concepts. This dissertation proposes the application of signal processing methods on physiological signals to extract from them features that can be processed by learning pattern recognition systems to provide cues about a person's affective state. In particular, combining physiological information sensed from a user's left hand in a non-invasive way with the pupil diameter information from an eye-tracking system may provide a computer with an awareness of its user's affective responses in the course of human-computer interactions. In this study an integrated hardware-software setup was developed to achieve automatic assessment of the affective status of a computer user. A computer-based "Paced Stroop Test" was designed as a stimulus to elicit emotional stress in the subject during the experiment. Four signals: the Galvanic Skin Response (GSR), the Blood Volume Pulse (BVP), the Skin Temperature (ST) and the Pupil Diameter (PD), were monitored and analyzed to differentiate affective states in the user. Several signal processing techniques were applied on the collected signals to extract their most relevant features. These features were analyzed with learning classification systems, to accomplish the affective state identification. Three learning algorithms: Naïve Bayes, Decision Tree and Support Vector Machine were applied to this identification process and their levels of classification accuracy were compared. The results achieved indicate that the physiological signals monitored do, in fact, have a strong correlation with the changes in the emotional states of the experimental subjects. These results also revealed that the inclusion of pupil diameter information significantly improved the performance of the emotion recognition system. ^

Enabling adaptability in service aggregates using transparent shaping techniques

Distributed applications are exposed as reusable components that are dynamically discovered and integrated to create new applications. These new applications, in the form of aggregate services, are vulnerable to failure due to the autonomous and distributed nature of their integrated components. This vulnerability creates the need for adaptability in aggregate services. The need for adaptation is accentuated for complex long-running applications as is found in scientific Grid computing, where distributed computing nodes may participate to solve computation and data-intensive problems. Such applications integrate services for coordinated problem solving in areas such as Bioinformatics. For such applications, when a constituent service fails, the application fails, even though there are other nodes that can substitute for the failed service. This concern is not addressed in the specification of high-level composition languages such as that of the Business Process Execution Language (BPEL). We propose an approach to transparently autonomizing existing BPEL processes in order to make them modifiable at runtime and more resilient to the failures in their execution environment. By transparent introduction of adaptive behavior, adaptation preserves the original business logic of the aggregate service and does not tangle the code for adaptive behavior with that of the aggregate service. The major contributions of this dissertation are: first, we assessed the effectiveness of BPEL language support in developing adaptive mechanisms. As a result, we identified the strengths and limitations of BPEL and came up with strategies to address those limitations. Second, we developed a technique to enhance existing BPEL processes transparently in order to support dynamic adaptation. We proposed a framework which uses transparent shaping and generative programming to make BPEL processes adaptive. Third, we developed a technique to dynamically discover and bind to substitute services. Our technique was evaluated and the result showed that dynamic utilization of components improves the flexibility of adaptive BPEL processes. Fourth, we developed an extensible policy-based technique to specify how to handle exceptional behavior. We developed a generic component that introduces adaptive behavior for multiple BPEL processes. Fifth, we identify ways to apply our work to facilitate adaptability in composite Grid services.

Towards simulation and emulation of large-scale computer networks

Developing analytical models that can accurately describe behaviors of Internet-scale networks is difficult. This is due, in part, to the heterogeneous structure, immense size and rapidly changing properties of today's networks. The lack of analytical models makes large-scale network simulation an indispensable tool for studying immense networks. However, large-scale network simulation has not been commonly used to study networks of Internet-scale. This can be attributed to three factors: 1) current large-scale network simulators are geared towards simulation research and not network research, 2) the memory required to execute an Internet-scale model is exorbitant, and 3) large-scale network models are difficult to validate. This dissertation tackles each of these problems. ^ First, this work presents a method for automatically enabling real-time interaction, monitoring, and control of large-scale network models. Network researchers need tools that allow them to focus on creating realistic models and conducting experiments. However, this should not increase the complexity of developing a large-scale network simulator. This work presents a systematic approach to separating the concerns of running large-scale network models on parallel computers and the user facing concerns of configuring and interacting with large-scale network models. ^ Second, this work deals with reducing memory consumption of network models. As network models become larger, so does the amount of memory needed to simulate them. This work presents a comprehensive approach to exploiting structural duplications in network models to dramatically reduce the memory required to execute large-scale network experiments. ^ Lastly, this work addresses the issue of validating large-scale simulations by integrating real protocols and applications into the simulation. With an emulation extension, a network simulator operating in real-time can run together with real-world distributed applications and services. As such, real-time network simulation not only alleviates the burden of developing separate models for applications in simulation, but as real systems are included in the network model, it also increases the confidence level of network simulation. This work presents a scalable and flexible framework to integrate real-world applications with real-time simulation.^

Leveraging symbiotic relationships for emulation of computer networks

The lack of analytical models that can accurately describe large-scale networked systems makes empirical experimentation indispensable for understanding complex behaviors. Research on network testbeds for testing network protocols and distributed services, including physical, emulated, and federated testbeds, has made steady progress. Although the success of these testbeds is undeniable, they fail to provide: 1) scalability, for handling large-scale networks with hundreds or thousands of hosts and routers organized in different scenarios, 2) flexibility, for testing new protocols or applications in diverse settings, and 3) inter-operability, for combining simulated and real network entities in experiments. This dissertation tackles these issues in three different dimensions. First, we present SVEET, a system that enables inter-operability between real and simulated hosts. In order to increase the scalability of networks under study, SVEET enables time-dilated synchronization between real hosts and the discrete-event simulator. Realistic TCP congestion control algorithms are implemented in the simulator to allow seamless interactions between real and simulated hosts. SVEET is validated via extensive experiments and its capabilities are assessed through case studies involving real applications. Second, we present PrimoGENI, a system that allows a distributed discrete-event simulator, running in real-time, to interact with real network entities in a federated environment. PrimoGENI greatly enhances the flexibility of network experiments, through which a great variety of network conditions can be reproduced to examine what-if questions. Furthermore, PrimoGENI performs resource management functions, on behalf of the user, for instantiating network experiments on shared infrastructures. Finally, to further increase the scalability of network testbeds to handle large-scale high-capacity networks, we present a novel symbiotic simulation approach. We present SymbioSim, a testbed for large-scale network experimentation where a high-performance simulation system closely cooperates with an emulation system in a mutually beneficial way. On the one hand, the simulation system benefits from incorporating the traffic metadata from real applications in the emulation system to reproduce the realistic traffic conditions. On the other hand, the emulation system benefits from receiving the continuous updates from the simulation system to calibrate the traffic between real applications. Specific techniques that support the symbiotic approach include: 1) a model downscaling scheme that can significantly reduce the complexity of the large-scale simulation model, resulting in an efficient emulation system for modulating the high-capacity network traffic between real applications; 2) a queuing network model for the downscaled emulation system to accurately represent the network effects of the simulated traffic; and 3) techniques for reducing the synchronization overhead between the simulation and emulation systems.

The relationship between selected standardized test scores and performance in advanced placement math and science exams: Analyzing the differential effectiveness of scores for course identification and placement

There is a national need to increase the STEM-related workforce. Among factors leading towards STEM careers include the number of advanced high school mathematics and science courses students complete. Florida's enrollment patterns in STEM-related Advanced Placement (AP) courses, however, reveal that only a small percentage of students enroll into these classes. Therefore, screening tools are needed to find more students for these courses, who are academically ready, yet have not been identified. The purpose of this study was to investigate the extent to which scores from a national standardized test, Preliminary Scholastic Assessment Test/ National Merit Qualifying Test (PSAT/NMSQT), in conjunction with and compared to a state-mandated standardized test, Florida Comprehensive Assessment Test (FCAT), are related to selected AP exam performance in Seminole County Public Schools. An ex post facto correlational study was conducted using 6,189 student records from the 2010 - 2012 academic years. Multiple regression analyses using simultaneous Full Model testing showed differential moderate to strong relationships between scores in eight of the nine AP courses (i.e., Biology, Environmental Science, Chemistry, Physics B, Physics C Electrical, Physics C Mechanical, Statistics, Calculus AB and BC) examined. For example, the significant unique contribution to overall variance in AP scores was a linear combination of PSAT Math (M), Critical Reading (CR) and FCAT Reading (R) for Biology and Environmental Science. Moderate relationships for Chemistry included a linear combination of PSAT M, W (Writing) and FCAT M; a combination of FCAT M and PSAT M was most significantly associated with Calculus AB performance. These findings have implications for both research and practice. FCAT scores, in conjunction with PSAT scores, can potentially be used for specific STEM-related AP courses, as part of a systematic approach towards AP course identification and placement. For courses with moderate to strong relationships, validation studies and development of expectancy tables, which estimate the probability of successful performance on these AP exams, are recommended. Also, findings established a need to examine other related research issues including, but not limited to, extensive longitudinal studies and analyses of other available or prospective standardized test scores.