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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
Multidimensional data have various representations. Thanks to their simplicity in modeling multidimensional data and the availability of various mathematical tools (such as tensor decompositions) that support multi-aspect analysis of such data, tensors are increasingly being used in many application domains including scientific data management, sensor data management, and social network data analysis. Relational model, on the other hand, enables semantic manipulation of data using relational operators, such as projection, selection, Cartesian-product, and set operators. For many multidimensional data applications, tensor operations as well as relational operations need to be supported throughout the data life cycle. In this thesis, we introduce a tensor-based relational data model (TRM), which enables both tensor- based data analysis and relational manipulations of multidimensional data, and define tensor-relational operations on this model. Then we introduce a tensor-relational data management system, so called, TensorDB. TensorDB is based on TRM, which brings together relational algebraic operations (for data manipulation and integration) and tensor algebraic operations (for data analysis). We develop optimization strategies for tensor-relational operations in both in-memory and in-database TensorDB. The goal of the TRM and TensorDB is to serve as a single environment that supports the entire life cycle of data; that is, data can be manipulated, integrated, processed, and analyzed.
ContributorsKim, Mijung (Author) / Candan, K. Selcuk (Thesis advisor) / Davulcu, Hasan (Committee member) / Sundaram, Hari (Committee member) / Ye, Jieping (Committee member) / Arizona State University (Publisher)
Created2014
Description
Recent efforts in data cleaning have focused mostly on problems like data deduplication, record matching, and data standardization; few of these focus on fixing incorrect attribute values in tuples. Correcting values in tuples is typically performed by a minimum cost repair of tuples that violate static constraints like CFDs (which have to be provided by domain experts, or learned from a clean sample of the database). In this thesis, I provide a method for correcting individual attribute values in a structured database using a Bayesian generative model and a statistical error model learned from the noisy database directly. I thus avoid the necessity for a domain expert or master data. I also show how to efficiently perform consistent query answering using this model over a dirty database, in case write permissions to the database are unavailable. A Map-Reduce architecture to perform this computation in a distributed manner is also shown. I evaluate these methods over both synthetic and real data.
ContributorsDe, Sushovan (Author) / Kambhampati, Subbarao (Thesis advisor) / Chen, Yi (Committee member) / Candan, K. Selcuk (Committee member) / Liu, Huan (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
This thesis deals with the analysis of interpersonal communication dynamics in online social networks and social media. Our central hypothesis is that communication dynamics between individuals manifest themselves via three key aspects: the information that is the content of communication, the social engagement i.e. the sociological framework emergent of the communication process, and the channel i.e. the media via which communication takes place. Communication dynamics have been of interest to researchers from multi-faceted domains over the past several decades. However, today we are faced with several modern capabilities encompassing a host of social media websites. These sites feature variegated interactional affordances, ranging from blogging, micro-blogging, sharing media elements as well as a rich set of social actions such as tagging, voting, commenting and so on. Consequently, these communication tools have begun to redefine the ways in which we exchange information, our modes of social engagement, and mechanisms of how the media characteristics impact our interactional behavior. The outcomes of this research are manifold. We present our contributions in three parts, corresponding to the three key organizing ideas. First, we have observed that user context is key to characterizing communication between a pair of individuals. However interestingly, the probability of future communication seems to be more sensitive to the context compared to the delay, which appears to be rather habitual. Further, we observe that diffusion of social actions in a network can be indicative of future information cascades; that might be attributed to social influence or homophily depending on the nature of the social action. Second, we have observed that different modes of social engagement lead to evolution of groups that have considerable predictive capability in characterizing external-world temporal occurrences, such as stock market dynamics as well as collective political sentiments. Finally, characterization of communication on rich media sites have shown that conversations that are deemed "interesting" appear to have consequential impact on the properties of the social network they are associated with: in terms of degree of participation of the individuals in future conversations, thematic diffusion as well as emergent cohesiveness in activity among the concerned participants in the network. Based on all these outcomes, we believe that this research can make significant contribution into a better understanding of how we communicate online and how it is redefining our collective sociological behavior.
ContributorsDe Choudhury, Munmun (Author) / Sundaram, Hari (Thesis advisor) / Candan, K. Selcuk (Committee member) / Liu, Huan (Committee member) / Watts, Duncan J. (Committee member) / Seligmann, Doree D. (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
Most existing approaches to complex event processing over streaming data rely on the assumption that the matches to the queries are rare and that the goal of the system is to identify these few matches within the incoming deluge of data. In many applications, such as stock market analysis and user credit card purchase pattern monitoring, however the matches to the user queries are in fact plentiful and the system has to efficiently sift through these many matches to locate only the few most preferable matches. In this work, we propose a complex pattern ranking (CPR) framework for specifying top-k pattern queries over streaming data, present new algorithms to support top-k pattern queries in data streaming environments, and verify the effectiveness and efficiency of the proposed algorithms. The developed algorithms identify top-k matching results satisfying both patterns as well as additional criteria. To support real-time processing of the data streams, instead of computing top-k results from scratch for each time window, we maintain top-k results dynamically as new events come and old ones expire. We also develop new top-k join execution strategies that are able to adapt to the changing situations (e.g., sorted and random access costs, join rates) without having to assume a priori presence of data statistics. Experiments show significant improvements over existing approaches.
ContributorsWang, Xinxin (Author) / Candan, K. Selcuk (Thesis advisor) / Chen, Yi (Committee member) / Davulcu, Hasan (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
Node proximity measures are commonly used for quantifying how nearby or otherwise related to two or more nodes in a graph are. Node significance measures are mainly used to find how much nodes are important in a graph. The measures of node proximity/significance have been highly effective in many predictions and applications. Despite their effectiveness, however, there are various shortcomings. One such shortcoming is a scalability problem due to their high computation costs on large size graphs and another problem on the measures is low accuracy when the significance of node and its degree in the graph are not related. The other problem is that their effectiveness is less when information for a graph is uncertain. For an uncertain graph, they require exponential computation costs to calculate ranking scores with considering all possible worlds.
In this thesis, I first introduce Locality-sensitive, Re-use promoting, approximate Personalized PageRank (LR-PPR) which is an approximate personalized PageRank calculating node rankings for the locality information for seeds without calculating the entire graph and reusing the precomputed locality information for different locality combinations. For the identification of locality information, I present Impact Neighborhood Indexing (INI) to find impact neighborhoods with nodes' fingerprints propagation on the network. For the accuracy challenge, I introduce Degree Decoupled PageRank (D2PR) technique to improve the effectiveness of PageRank based knowledge discovery, especially considering the significance of neighbors and degree of a given node. To tackle the uncertain challenge, I introduce Uncertain Personalized PageRank (UPPR) to approximately compute personalized PageRank values on uncertainties of edge existence and Interval Personalized PageRank with Integration (IPPR-I) and Interval Personalized PageRank with Mean (IPPR-M) to compute ranking scores for the case when uncertainty exists on edge weights as interval values.
In this thesis, I first introduce Locality-sensitive, Re-use promoting, approximate Personalized PageRank (LR-PPR) which is an approximate personalized PageRank calculating node rankings for the locality information for seeds without calculating the entire graph and reusing the precomputed locality information for different locality combinations. For the identification of locality information, I present Impact Neighborhood Indexing (INI) to find impact neighborhoods with nodes' fingerprints propagation on the network. For the accuracy challenge, I introduce Degree Decoupled PageRank (D2PR) technique to improve the effectiveness of PageRank based knowledge discovery, especially considering the significance of neighbors and degree of a given node. To tackle the uncertain challenge, I introduce Uncertain Personalized PageRank (UPPR) to approximately compute personalized PageRank values on uncertainties of edge existence and Interval Personalized PageRank with Integration (IPPR-I) and Interval Personalized PageRank with Mean (IPPR-M) to compute ranking scores for the case when uncertainty exists on edge weights as interval values.
ContributorsKim, Jung Hyun (Author) / Candan, K. Selcuk (Thesis advisor) / Davulcu, Hasan (Committee member) / Tong, Hanghang (Committee member) / Sapino, Maria Luisa (Committee member) / Arizona State University (Publisher)
Created2017