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Description
Biological systems are complex in many dimensions as endless transportation and communication networks all function simultaneously. Our ability to intervene within both healthy and diseased systems is tied directly to our ability to understand and model core functionality. The progress in increasingly accurate and thorough high-throughput measurement technologies has provided a deluge of data from which we may attempt to infer a representation of the true genetic regulatory system. A gene regulatory network model, if accurate enough, may allow us to perform hypothesis testing in the form of computational experiments. Of great importance to modeling accuracy is the acknowledgment of biological contexts within the models -- i.e. recognizing the heterogeneous nature of the true biological system and the data it generates. This marriage of engineering, mathematics and computer science with systems biology creates a cycle of progress between computer simulation and lab experimentation, rapidly translating interventions and treatments for patients from the bench to the bedside. This dissertation will first discuss the landscape for modeling the biological system, explore the identification of targets for intervention in Boolean network models of biological interactions, and explore context specificity both in new graphical depictions of models embodying context-specific genomic regulation and in novel analysis approaches designed to reveal embedded contextual information. Overall, the dissertation will explore a spectrum of biological modeling with a goal towards therapeutic intervention, with both formal and informal notions of biological context, in such a way that will enable future work to have an even greater impact in terms of direct patient benefit on an individualized level.
ContributorsVerdicchio, Michael (Author) / Kim, Seungchan (Thesis advisor) / Baral, Chitta (Committee member) / Stolovitzky, Gustavo (Committee member) / Collofello, James (Committee member) / Arizona State University (Publisher)
Created2013
Description
Laboratory automation systems have seen a lot of technological advances in recent times. As a result, the software that is written for them are becoming increasingly sophisticated. Existing software architectures and standards are targeted to a wider domain of software development and need to be customized in order to use them for developing software for laboratory automation systems. This thesis proposes an architecture that is based on existing software architectural paradigms and is specifically tailored to developing software for a laboratory automation system. The architecture is based on fairly autonomous software components that can be distributed across multiple computers. The components in the architecture make use of asynchronous communication methodologies that are facilitated by passing messages between one another. The architecture can be used to develop software that is distributed, responsive and thread-safe. The thesis also proposes a framework that has been developed to implement the ideas proposed by the architecture. The framework is used to develop software that is scalable, distributed, responsive and thread-safe. The framework currently has components to control very commonly used laboratory automation devices such as mechanical stages, cameras, and also to do common laboratory automation functionalities such as imaging.
ContributorsKuppuswamy, Venkataramanan (Author) / Meldrum, Deirdre (Thesis advisor) / Collofello, James (Thesis advisor) / Sarjoughian, Hessam S. (Committee member) / Johnson, Roger (Committee member) / Arizona State University (Publisher)
Created2012
Description
The pay-as-you-go economic model of cloud computing increases the visibility, traceability, and verifiability of software costs. Application developers must understand how their software uses resources when running in the cloud in order to stay within budgeted costs and/or produce expected profits. Cloud computing's unique economic model also leads naturally to an earn-as-you-go profit model for many cloud based applications. These applications can benefit from low level analyses for cost optimization and verification. Testing cloud applications to ensure they meet monetary cost objectives has not been well explored in the current literature. When considering revenues and costs for cloud applications, the resource economic model can be scaled down to the transaction level in order to associate source code with costs incurred while running in the cloud. Both static and dynamic analysis techniques can be developed and applied to understand how and where cloud applications incur costs. Such analyses can help optimize (i.e. minimize) costs and verify that they stay within expected tolerances. An adaptation of Worst Case Execution Time (WCET) analysis is presented here to statically determine worst case monetary costs of cloud applications. This analysis is used to produce an algorithm for determining control flow paths within an application that can exceed a given cost threshold. The corresponding results are used to identify path sections that contribute most to cost excess. A hybrid approach for determining cost excesses is also presented that is comprised mostly of dynamic measurements but that also incorporates calculations that are based on the static analysis approach. This approach uses operational profiles to increase the precision and usefulness of the calculations.
ContributorsBuell, Kevin, Ph.D (Author) / Collofello, James (Thesis advisor) / Davulcu, Hasan (Committee member) / Lindquist, Timothy (Committee member) / Sen, Arunabha (Committee member) / Arizona State University (Publisher)
Created2012
Description
Access control is necessary for information assurance in many of today's applications such as banking and electronic health record. Access control breaches are critical security problems that can result from unintended and improper implementation of security policies. Security testing can help identify security vulnerabilities early and avoid unexpected expensive cost in handling breaches for security architects and security engineers. The process of security testing which involves creating tests that effectively examine vulnerabilities is a challenging task. Role-Based Access Control (RBAC) has been widely adopted to support fine-grained access control. However, in practice, due to its complexity including role management, role hierarchy with hundreds of roles, and their associated privileges and users, systematically testing RBAC systems is crucial to ensure the security in various domains ranging from cyber-infrastructure to mission-critical applications. In this thesis, we introduce i) a security testing technique for RBAC systems considering the principle of maximum privileges, the structure of the role hierarchy, and a new security test coverage criterion; ii) a MTBDD (Multi-Terminal Binary Decision Diagram) based representation of RBAC security policy including RHMTBDD (Role Hierarchy MTBDD) to efficiently generate effective positive and negative security test cases; and iii) a security testing framework which takes an XACML-based RBAC security policy as an input, parses it into a RHMTBDD representation and then generates positive and negative test cases. We also demonstrate the efficacy of our approach through case studies.
ContributorsGupta, Poonam (Author) / Ahn, Gail-Joon (Thesis advisor) / Collofello, James (Committee member) / Huang, Dijiang (Committee member) / Arizona State University (Publisher)
Created2014
Description
Given the process of tumorigenesis, biological signaling pathways have become of interest in the field of oncology. Many of the regulatory mechanisms that are altered in cancer are directly related to signal transduction and cellular communication. Thus, identifying signaling pathways that have become deregulated may provide useful information to better understanding altered regulatory mechanisms within cancer. Many methods that have been created to measure the distinct activity of signaling pathways have relied strictly upon transcription profiles. With advancements in comparative genomic hybridization techniques, copy number data has become extremely useful in providing valuable information pertaining to the genomic landscape of cancer. The purpose of this thesis is to develop a methodology that incorporates both gene expression and copy number data to identify signaling pathways that have become deregulated in cancer. The central idea is that copy number data may significantly assist in identifying signaling pathway deregulation by justifying the aberrant activity being measured in gene expression profiles. This method was then applied to four different subtypes of breast cancer resulting in the identification of signaling pathways associated with distinct functionalities for each of the breast cancer subtypes.
ContributorsTrevino, Robert (Author) / Kim, Seungchan (Thesis advisor) / Ringner, Markus (Committee member) / Liu, Huan (Committee member) / Arizona State University (Publisher)
Created2011
Description
In many classication problems data samples cannot be collected easily, example in drug trials, biological experiments and study on cancer patients. In many situations the data set size is small and there are many outliers. When classifying such data, example cancer vs normal patients the consequences of mis-classication are probably more important than any other data type, because the data point could be a cancer patient or the classication decision could help determine what gene might be over expressed and perhaps a cause of cancer. These mis-classications are typically higher in the presence of outlier data points. The aim of this thesis is to develop a maximum margin classier that is suited to address the lack of robustness of discriminant based classiers (like the Support Vector Machine (SVM)) to noise and outliers. The underlying notion is to adopt and develop a natural loss function that is more robust to outliers and more representative of the true loss function of the data. It is demonstrated experimentally that SVM's are indeed susceptible to outliers and that the new classier developed, here coined as Robust-SVM (RSVM), is superior to all studied classier on the synthetic datasets. It is superior to the SVM in both the synthetic and experimental data from biomedical studies and is competent to a classier derived on similar lines when real life data examples are considered.
ContributorsGupta, Sidharth (Author) / Kim, Seungchan (Thesis advisor) / Welfert, Bruno (Committee member) / Li, Baoxin (Committee member) / Arizona State University (Publisher)
Created2011
Description
Reverse engineering gene regulatory networks (GRNs) is an important problem in the domain of Systems Biology. Learning GRNs is challenging due to the inherent complexity of the real regulatory networks and the heterogeneity of samples in available biomedical data. Real world biological data are commonly collected from broad surveys (profiling studies) and aggregate highly heterogeneous biological samples. Popular methods to learn GRNs simplistically assume a single universal regulatory network corresponding to available data. They neglect regulatory network adaptation due to change in underlying conditions and cellular phenotype or both. This dissertation presents a novel computational framework to learn common regulatory interactions and networks underlying the different sets of relatively homogeneous samples from real world biological data. The characteristic set of samples/conditions and corresponding regulatory interactions defines the cellular context (context). Context, in this dissertation, represents the deterministic transcriptional activity within the specific cellular regulatory mechanism. The major contributions of this framework include - modeling and learning context specific GRNs; associating enriched samples with contexts to interpret contextual interactions using biological knowledge; pruning extraneous edges from the context-specific GRN to improve the precision of the final GRNs; integrating multisource data to learn inter and intra domain interactions and increase confidence in obtained GRNs; and finally, learning combinatorial conditioning factors from the data to identify regulatory cofactors. The framework, Expattern, was applied to both real world and synthetic data. Interesting insights were obtained into mechanism of action of drugs on analysis of NCI60 drug activity and gene expression data. Application to refractory cancer data and Glioblastoma multiforme yield GRNs that were readily annotated with context-specific phenotypic information. Refractory cancer GRNs also displayed associations between distinct cancers, not observed through only clustering. Performance comparisons on multi-context synthetic data show the framework Expattern performs better than other comparable methods.
ContributorsSen, Ina (Author) / Kim, Seungchan (Thesis advisor) / Baral, Chitta (Committee member) / Bittner, Michael (Committee member) / Konjevod, Goran (Committee member) / Arizona State University (Publisher)
Created2011
Description
Introductory programming courses, also known as CS1, have a specific set of expected outcomes related to the learning of the most basic and essential computational concepts in computer science (CS). However, two of the most often heard complaints in such courses are that (1) they are divorced from the reality of application and (2) they make the learning of the basic concepts tedious. The concepts introduced in CS1 courses are highly abstract and not easily comprehensible. In general, the difficulty is intrinsic to the field of computing, often described as "too mathematical or too abstract." This dissertation presents a small-scale mixed method study conducted during the fall 2009 semester of CS1 courses at Arizona State University. This study explored and assessed students' comprehension of three core computational concepts - abstraction, arrays of objects, and inheritance - in both algorithm design and problem solving. Through this investigation students' profiles were categorized based on their scores and based on their mistakes categorized into instances of five computational thinking concepts: abstraction, algorithm, scalability, linguistics, and reasoning. It was shown that even though the notion of computational thinking is not explicit in the curriculum, participants possessed and/or developed this skill through the learning and application of the CS1 core concepts. Furthermore, problem-solving experiences had a direct impact on participants' knowledge skills, explanation skills, and confidence. Implications for teaching CS1 and for future research are also considered.
ContributorsBillionniere, Elodie V (Author) / Collofello, James (Thesis advisor) / Ganesh, Tirupalavanam G. (Thesis advisor) / VanLehn, Kurt (Committee member) / Burleson, Winslow (Committee member) / Arizona State University (Publisher)
Created2011
Description
Threshold logic has been studied by at least two independent group of researchers. One group of researchers studied threshold logic with the intention of building threshold logic circuits. The earliest research to this end was done in the 1960's. The major work at that time focused on studying mathematical properties of threshold logic as no efficient circuit implementations of threshold logic were available. Recently many post-CMOS (Complimentary Metal Oxide Semiconductor) technologies that implement threshold logic have been proposed along with efficient CMOS implementations. This has renewed the effort to develop efficient threshold logic design automation techniques. This work contributes to this ongoing effort. Another group studying threshold logic did so, because the building block of neural networks - the Perceptron, is identical to the threshold element implementing a threshold function. Neural networks are used for various purposes as data classifiers. This work contributes tangentially to this field by proposing new methods and techniques to study and analyze functions implemented by a Perceptron After completion of the Human Genome Project, it has become evident that most biological phenomenon is not caused by the action of single genes, but due to the complex interaction involving a system of genes. In recent times, the `systems approach' for the study of gene systems is gaining popularity. Many different theories from mathematics and computer science has been used for this purpose. Among the systems approaches, the Boolean logic gene model has emerged as the current most popular discrete gene model. This work proposes a new gene model based on threshold logic functions (which are a subset of Boolean logic functions). The biological relevance and utility of this model is argued illustrated by using it to model different in-vivo as well as in-silico gene systems.
ContributorsLinge Gowda, Tejaswi (Author) / Vrudhula, Sarma (Thesis advisor) / Shrivastava, Aviral (Committee member) / Chatha, Karamvir (Committee member) / Kim, Seungchan (Committee member) / Arizona State University (Publisher)
Created2012
Description
Machine learning tutorials often employ an application and runtime specific solution for a given problem in which users are expected to have a broad understanding of data analysis and software programming. This thesis focuses on designing and implementing a new, hands-on approach to teaching machine learning by streamlining the process of generating Inertial Movement Unit (IMU) data from multirotor flight sessions, training a linear classifier, and applying said classifier to solve Multi-rotor Activity Recognition (MAR) problems in an online lab setting. MAR labs leverage cloud computing and data storage technologies to host a versatile environment capable of logging, orchestrating, and visualizing the solution for an MAR problem through a user interface. MAR labs extends Arizona State University’s Visual IoT/Robotics Programming Language Environment (VIPLE) as a control platform for multi-rotors used in data collection. VIPLE is a platform developed for teaching computational thinking, visual programming, Internet of Things (IoT) and robotics application development. As a part of this education platform, this work also develops a 3D simulator capable of simulating the programmable behaviors of a robot within a maze environment and builds a physical quadrotor for use in MAR lab experiments.
ContributorsDe La Rosa, Matthew Lee (Author) / Chen, Yinong (Thesis advisor) / Collofello, James (Committee member) / Huang, Dijiang (Committee member) / Arizona State University (Publisher)
Created2018