Matching Items (6)
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- All Subjects: Logic programming
- Creators: Baral, Chitta
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
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
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
Different logic-based knowledge representation formalisms have different limitations either with respect to expressivity or with respect to computational efficiency. First-order logic, which is the basis of Description Logics (DLs), is not suitable for defeasible reasoning due to its monotonic nature. The nonmonotonic formalisms that extend first-order logic, such as circumscription and default logic, are expressive but lack efficient implementations. The nonmonotonic formalisms that are based on the declarative logic programming approach, such as Answer Set Programming (ASP), have efficient implementations but are not expressive enough for representing and reasoning with open domains. This dissertation uses the first-order stable model semantics, which extends both first-order logic and ASP, to relate circumscription to ASP, and to integrate DLs and ASP, thereby partially overcoming the limitations of the formalisms. By exploiting the relationship between circumscription and ASP, well-known action formalisms, such as the situation calculus, the event calculus, and Temporal Action Logics, are reformulated in ASP. The advantages of these reformulations are shown with respect to the generality of the reasoning tasks that can be handled and with respect to the computational efficiency. The integration of DLs and ASP presented in this dissertation provides a framework for integrating rules and ontologies for the semantic web. This framework enables us to perform nonmonotonic reasoning with DL knowledge bases. Observing the need to integrate action theories and ontologies, the above results are used to reformulate the problem of integrating action theories and ontologies as a problem of integrating rules and ontologies, thus enabling us to use the computational tools developed in the context of the latter for the former.
ContributorsPalla, Ravi (Author) / Lee, Joohyung (Thesis advisor) / Baral, Chitta (Committee member) / Kambhampati, Subbarao (Committee member) / Lifschitz, Vladimir (Committee member) / Arizona State University (Publisher)
Created2012
Description
Goal specification is an important aspect of designing autonomous agents. A goal does not only refer to the set of states for the agent to reach. A goal also defines restrictions on the paths the agent should follow. Temporal logics are widely used in goal specification. However, they lack the ability to represent goals in a non-deterministic domain, goals that change non-monotonically, and goals with preferences. This dissertation defines new goal specification languages by extending temporal logics to address these issues. First considered is the goal specification in non-deterministic domains, in which an agent following a policy leads to a set of paths. A logic is proposed to distinguish paths of the agent from all paths in the domain. In addition, to address the need of comparing policies for finding the best ones, a language capable of quantifying over policies is proposed. As policy structures of agents play an important role in goal specification, languages are also defined by considering different policy structures. Besides, after an agent is given an initial goal, the agent may change its expectations or the domain may change, thus goals that are previously specified may need to be further updated, revised, partially retracted, or even completely changed. Non-monotonic goal specification languages that can make these changes in an elaboration tolerant manner are needed. Two languages that rely on labeling sub-formulas and connecting multiple rules are developed to address non-monotonicity in goal specification. Also, agents may have preferential relations among sub-goals, and the preferential relations may change as agents achieve other sub-goals. By nesting a comparison operator with other temporal operators, a language with dynamic preferences is proposed. Various goals that cannot be expressed in other languages are expressed in the proposed languages. Finally, plans are given for some goals specified in the proposed languages.
ContributorsZhao, Jicheng (Author) / Baral, Chitta (Thesis advisor) / Kambhampati, Subbarao (Committee member) / Lee, Joohyung (Committee member) / Lifschitz, Vladimir (Committee member) / Liu, Huan (Committee member) / Arizona State University (Publisher)
Created2010
Description
As we migrate into an era of personalized medicine, understanding how bio-molecules interact with one another to form cellular systems is one of the key focus areas of systems biology. Several challenges such as the dynamic nature of cellular systems, uncertainty due to environmental influences, and the heterogeneity between individual patients render this a difficult task. In the last decade, several algorithms have been proposed to elucidate cellular systems from data, resulting in numerous data-driven hypotheses. However, due to the large number of variables involved in the process, many of which are unknown or not measurable, such computational approaches often lead to a high proportion of false positives. This renders interpretation of the data-driven hypotheses extremely difficult. Consequently, a dismal proportion of these hypotheses are subject to further experimental validation, eventually limiting their potential to augment existing biological knowledge. This dissertation develops a framework of computational methods for the analysis of such data-driven hypotheses leveraging existing biological knowledge. Specifically, I show how biological knowledge can be mapped onto these hypotheses and subsequently augmented through novel hypotheses. Biological hypotheses are learnt in three levels of abstraction -- individual interactions, functional modules and relationships between pathways, corresponding to three complementary aspects of biological systems. The computational methods developed in this dissertation are applied to high throughput cancer data, resulting in novel hypotheses with potentially significant biological impact.
ContributorsRamesh, Archana (Author) / Kim, Seungchan (Thesis advisor) / Langley, Patrick W (Committee member) / Baral, Chitta (Committee member) / Kiefer, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2012