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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

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
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Description
Action language C+ is a formalism for describing properties of actions, which is based on nonmonotonic causal logic. The definite fragment of C+ is implemented in the Causal Calculator (CCalc), which is based on the reduction of nonmonotonic causal logic to propositional logic. This thesis describes the language

Action language C+ is a formalism for describing properties of actions, which is based on nonmonotonic causal logic. The definite fragment of C+ is implemented in the Causal Calculator (CCalc), which is based on the reduction of nonmonotonic causal logic to propositional logic. This thesis describes the language of CCalc in terms of answer set programming (ASP), based on the translation of nonmonotonic causal logic to formulas under the stable model semantics. I designed a standard library which describes the constructs of the input language of CCalc in terms of ASP, allowing a simple modular method to represent CCalc input programs in the language of ASP. Using the combination of system F2LP and answer set solvers, this method achieves functionality close to that of CCalc while taking advantage of answer set solvers to yield efficient computation that is orders of magnitude faster than CCalc for many benchmark examples. In support of this, I created an automated translation system Cplus2ASP that implements the translation and encoding method and automatically invokes the necessary software to solve the translated input programs.
ContributorsCasolary, Michael (Author) / Lee, Joohyung (Thesis advisor) / Ahn, Gail-Joon (Committee member) / Baral, Chitta (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Functional magnetic resonance imaging (fMRI) has been widely used to measure the retinotopic organization of early visual cortex in the human brain. Previous studies have identified multiple visual field maps (VFMs) based on statistical analysis of fMRI signals, but the resulting geometry has not been fully characterized with mathematical models.

Functional magnetic resonance imaging (fMRI) has been widely used to measure the retinotopic organization of early visual cortex in the human brain. Previous studies have identified multiple visual field maps (VFMs) based on statistical analysis of fMRI signals, but the resulting geometry has not been fully characterized with mathematical models. This thesis explores using concepts from computational conformal geometry to create a custom software framework for examining and generating quantitative mathematical models for characterizing the geometry of early visual areas in the human brain. The software framework includes a graphical user interface built on top of a selected core conformal flattening algorithm and various software tools compiled specifically for processing and examining retinotopic data. Three conformal flattening algorithms were implemented and evaluated for speed and how well they preserve the conformal metric. All three algorithms performed well in preserving the conformal metric but the speed and stability of the algorithms varied. The software framework performed correctly on actual retinotopic data collected using the standard travelling-wave experiment. Preliminary analysis of the Beltrami coefficient for the early data set shows that selected regions of V1 that contain reasonably smooth eccentricity and polar angle gradients do show significant local conformality, warranting further investigation of this approach for analysis of early and higher visual cortex.
ContributorsTa, Duyan (Author) / Wang, Yalin (Thesis advisor) / Maciejewski, Ross (Committee member) / Wonka, Peter (Committee member) / Arizona State University (Publisher)
Created2013
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Description
In blindness research, the corpus callosum (CC) is the most frequently studied sub-cortical structure, due to its important involvement in visual processing. While most callosal analyses from brain structural magnetic resonance images (MRI) are limited to the 2D mid-sagittal slice, we propose a novel framework to capture a complete set

In blindness research, the corpus callosum (CC) is the most frequently studied sub-cortical structure, due to its important involvement in visual processing. While most callosal analyses from brain structural magnetic resonance images (MRI) are limited to the 2D mid-sagittal slice, we propose a novel framework to capture a complete set of 3D morphological differences in the corpus callosum between two groups of subjects. The CCs are segmented from whole brain T1-weighted MRI and modeled as 3D tetrahedral meshes. The callosal surface is divided into superior and inferior patches on which we compute a volumetric harmonic field by solving the Laplace's equation with Dirichlet boundary conditions. We adopt a refined tetrahedral mesh to compute the Laplacian operator, so our computation can achieve sub-voxel accuracy. Thickness is estimated by tracing the streamlines in the harmonic field. We combine areal changes found using surface tensor-based morphometry and thickness information into a vector at each vertex to be used as a metric for the statistical analysis. Group differences are assessed on this combined measure through Hotelling's T2 test. The method is applied to statistically compare three groups consisting of: congenitally blind (CB), late blind (LB; onset > 8 years old) and sighted (SC) subjects. Our results reveal significant differences in several regions of the CC between both blind groups and the sighted groups; and to a lesser extent between the LB and CB groups. These results demonstrate the crucial role of visual deprivation during the developmental period in reshaping the structural architecture of the CC.
ContributorsXu, Liang (Author) / Wang, Yalin (Thesis advisor) / Maciejewski, Ross (Committee member) / Ye, Jieping (Committee member) / Arizona State University (Publisher)
Created2013
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Description
In this dissertation I develop a deep theory of temporal planning well-suited to analyzing, understanding, and improving the state of the art implementations (as of 2012). At face-value the work is strictly theoretical; nonetheless its impact is entirely real and practical. The easiest portion of that impact to highlight concerns

In this dissertation I develop a deep theory of temporal planning well-suited to analyzing, understanding, and improving the state of the art implementations (as of 2012). At face-value the work is strictly theoretical; nonetheless its impact is entirely real and practical. The easiest portion of that impact to highlight concerns the notable improvements to the format of the temporal fragment of the International Planning Competitions (IPCs). Particularly: the theory I expound upon here is the primary cause of--and justification for--the altered (i) selection of benchmark problems, and (ii) notion of "winning temporal planner". For higher level motivation: robotics, web service composition, industrial manufacturing, business process management, cybersecurity, space exploration, deep ocean exploration, and logistics all benefit from applying domain-independent automated planning technique. Naturally, actually carrying out such case studies has much to offer. For example, we may extract the lesson that reasoning carefully about deadlines is rather crucial to planning in practice. More generally, effectively automating specifically temporal planning is well-motivated from applications. Entirely abstractly, the aim is to improve the theory of automated temporal planning by distilling from its practice. My thesis is that the key feature of computational interest is concurrency. To support, I demonstrate by way of compilation methods, worst-case counting arguments, and analysis of algorithmic properties such as completeness that the more immediately pressing computational obstacles (facing would-be temporal generalizations of classical planning systems) can be dealt with in theoretically efficient manner. So more accurately the technical contribution here is to demonstrate: The computationally significant obstacle to automated temporal planning that remains is just concurrency.
ContributorsCushing, William Albemarle (Author) / Kambhampati, Subbarao (Thesis advisor) / Weld, Daniel S. (Committee member) / Smith, David E. (Committee member) / Baral, Chitta (Committee member) / Davalcu, Hasan (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Sparsity has become an important modeling tool in areas such as genetics, signal and audio processing, medical image processing, etc. Via the penalization of l-1 norm based regularization, the structured sparse learning algorithms can produce highly accurate models while imposing various predefined structures on the data, such as feature groups

Sparsity has become an important modeling tool in areas such as genetics, signal and audio processing, medical image processing, etc. Via the penalization of l-1 norm based regularization, the structured sparse learning algorithms can produce highly accurate models while imposing various predefined structures on the data, such as feature groups or graphs. In this thesis, I first propose to solve a sparse learning model with a general group structure, where the predefined groups may overlap with each other. Then, I present three real world applications which can benefit from the group structured sparse learning technique. In the first application, I study the Alzheimer's Disease diagnosis problem using multi-modality neuroimaging data. In this dataset, not every subject has all data sources available, exhibiting an unique and challenging block-wise missing pattern. In the second application, I study the automatic annotation and retrieval of fruit-fly gene expression pattern images. Combined with the spatial information, sparse learning techniques can be used to construct effective representation of the expression images. In the third application, I present a new computational approach to annotate developmental stage for Drosophila embryos in the gene expression images. In addition, it provides a stage score that enables one to more finely annotate each embryo so that they are divided into early and late periods of development within standard stage demarcations. Stage scores help us to illuminate global gene activities and changes much better, and more refined stage annotations improve our ability to better interpret results when expression pattern matches are discovered between genes.
ContributorsYuan, Lei (Author) / Ye, Jieping (Thesis advisor) / Wang, Yalin (Committee member) / Xue, Guoliang (Committee member) / Kumar, Sudhir (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Linear Temporal Logic is gaining increasing popularity as a high level specification language for robot motion planning due to its expressive power and scalability of LTL control synthesis algorithms. This formalism, however, requires expert knowledge and makes it inaccessible to non-expert users. This thesis introduces a graphical specification environment to

Linear Temporal Logic is gaining increasing popularity as a high level specification language for robot motion planning due to its expressive power and scalability of LTL control synthesis algorithms. This formalism, however, requires expert knowledge and makes it inaccessible to non-expert users. This thesis introduces a graphical specification environment to create high level motion plans to control robots in the field by converting a visual representation of the motion/task plan into a Linear Temporal Logic (LTL) specification. The visual interface is built on the Android tablet platform and provides functionality to create task plans through a set of well defined gestures and on screen controls. It uses the notion of waypoints to quickly and efficiently describe the motion plan and enables a variety of complex Linear Temporal Logic specifications to be described succinctly and intuitively by the user without the need for the knowledge and understanding of LTL specification. Thus, it opens avenues for its use by personnel in military, warehouse management, and search and rescue missions. This thesis describes the construction of LTL for various scenarios used for robot navigation using the visual interface developed and leverages the use of existing LTL based motion planners to carry out the task plan by a robot.
ContributorsSrinivas, Shashank (Author) / Fainekos, Georgios (Thesis advisor) / Baral, Chitta (Committee member) / Burleson, Winslow (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Answer Set Programming (ASP) is one of the most prominent and successful knowledge representation paradigms. The success of ASP is due to its expressive non-monotonic modeling language and its efficient computational methods originating from building propositional satisfiability solvers. The wide adoption of ASP has motivated several extensions to its modeling

Answer Set Programming (ASP) is one of the most prominent and successful knowledge representation paradigms. The success of ASP is due to its expressive non-monotonic modeling language and its efficient computational methods originating from building propositional satisfiability solvers. The wide adoption of ASP has motivated several extensions to its modeling language in order to enhance expressivity, such as incorporating aggregates and interfaces with ontologies. Also, in order to overcome the grounding bottleneck of computation in ASP, there are increasing interests in integrating ASP with other computing paradigms, such as Constraint Programming (CP) and Satisfiability Modulo Theories (SMT). Due to the non-monotonic nature of the ASP semantics, such enhancements turned out to be non-trivial and the existing extensions are not fully satisfactory. We observe that one main reason for the difficulties rooted in the propositional semantics of ASP, which is limited in handling first-order constructs (such as aggregates and ontologies) and functions (such as constraint variables in CP and SMT) in natural ways. This dissertation presents a unifying view on these extensions by viewing them as instances of formulas with generalized quantifiers and intensional functions. We extend the first-order stable model semantics by by Ferraris, Lee, and Lifschitz to allow generalized quantifiers, which cover aggregate, DL-atoms, constraints and SMT theory atoms as special cases. Using this unifying framework, we study and relate different extensions of ASP. We also present a tight integration of ASP with SMT, based on which we enhance action language C+ to handle reasoning about continuous changes. Our framework yields a systematic approach to study and extend non-monotonic languages.
ContributorsMeng, Yunsong (Author) / Lee, Joohyung (Thesis advisor) / Ahn, Gail-Joon (Committee member) / Baral, Chitta (Committee member) / Fainekos, Georgios (Committee member) / Lifschitz, Vladimir (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Automating aspects of biocuration through biomedical information extraction could significantly impact biomedical research by enabling greater biocuration throughput and improving the feasibility of a wider scope. An important step in biomedical information extraction systems is named entity recognition (NER), where mentions of entities such as proteins and diseases are located

Automating aspects of biocuration through biomedical information extraction could significantly impact biomedical research by enabling greater biocuration throughput and improving the feasibility of a wider scope. An important step in biomedical information extraction systems is named entity recognition (NER), where mentions of entities such as proteins and diseases are located within natural-language text and their semantic type is determined. This step is critical for later tasks in an information extraction pipeline, including normalization and relationship extraction. BANNER is a benchmark biomedical NER system using linear-chain conditional random fields and the rich feature set approach. A case study with BANNER locating genes and proteins in biomedical literature is described. The first corpus for disease NER adequate for use as training data is introduced, and employed in a case study of disease NER. The first corpus locating adverse drug reactions (ADRs) in user posts to a health-related social website is also described, and a system to locate and identify ADRs in social media text is created and evaluated. The rich feature set approach to creating NER feature sets is argued to be subject to diminishing returns, implying that additional improvements may require more sophisticated methods for creating the feature set. This motivates the first application of multivariate feature selection with filters and false discovery rate analysis to biomedical NER, resulting in a feature set at least 3 orders of magnitude smaller than the set created by the rich feature set approach. Finally, two novel approaches to NER by modeling the semantics of token sequences are introduced. The first method focuses on the sequence content by using language models to determine whether a sequence resembles entries in a lexicon of entity names or text from an unlabeled corpus more closely. The second method models the distributional semantics of token sequences, determining the similarity between a potential mention and the token sequences from the training data by analyzing the contexts where each sequence appears in a large unlabeled corpus. The second method is shown to improve the performance of BANNER on multiple data sets.
ContributorsLeaman, James Robert (Author) / Gonzalez, Graciela (Thesis advisor) / Baral, Chitta (Thesis advisor) / Cohen, Kevin B (Committee member) / Liu, Huan (Committee member) / Ye, Jieping (Committee member) / Arizona State University (Publisher)
Created2013
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Description
There has been a lot of research in the field of artificial intelligence about thinking machines. Alan Turing proposed a test to observe a machine's intelligent behaviour with respect to natural language conversation. The Winograd schema challenge is suggested as an alternative, to the Turing test. It needs inferencing capabilities,

There has been a lot of research in the field of artificial intelligence about thinking machines. Alan Turing proposed a test to observe a machine's intelligent behaviour with respect to natural language conversation. The Winograd schema challenge is suggested as an alternative, to the Turing test. It needs inferencing capabilities, reasoning abilities and background knowledge to get the answer right. It involves a coreference resolution task in which a machine is given a sentence containing a situation which involves two entities, one pronoun and some more information about the situation and the machine has to come up with the right resolution of a pronoun to one of the entities. The complexity of the task is increased with the fact that the Winograd sentences are not constrained by one domain or specific sentence structure and it also contains a lot of human proper names. This modification makes the task of association of entities, to one particular word in the sentence, to derive the answer, difficult. I have developed a pronoun resolver system for the confined domain Winograd sentences. I have developed a classifier or filter which takes input sentences and decides to accept or reject them based on a particular criteria. Once the sentence is accepted. I run parsers on it to obtain the detailed analysis. Furthermore I have developed four answering modules which use world knowledge and inferencing mechanisms to try and resolve the pronoun. The four techniques I use are : ConceptNet knowledgebase, Search engine pattern counts,Narrative event chains and sentiment analysis. I have developed a particular aggregation mechanism for the answers from these modules to arrive at a final answer. I have used caching technique for the association relations that I obtain for different modules, so as to boost the performance. I run my system on the standard ‘nyu dataset’ of Winograd sentences and questions. This dataset is then restricted, by my classifier, to 90 sentences. I evaluate my system on this 90 sentence dataset. When I compare my results against the state of the art system on the same dataset, I get nearly 4.5 % improvement in the restricted domain.
ContributorsBudukh, Tejas Ulhas (Author) / Baral, Chitta (Thesis advisor) / VanLehn, Kurt (Committee member) / Davulcu, Hasan (Committee member) / Arizona State University (Publisher)
Created2013