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- All Subjects: Computer Science
- Creators: Barrett, The Honors College
- Creators: Baral, Chitta
- Creators: Fainekos, Georgios
Description
Genes have widely different pertinences to the etiology and pathology of diseases. Thus, they can be ranked according to their disease-significance on a genomic scale, which is the subject of gene prioritization. Given a set of genes known to be related to a disease, it is reasonable to use them as a basis to determine the significance of other candidate genes, which will then be ranked based on the association they exhibit with respect to the given set of known genes. Experimental and computational data of various kinds have different reliability and relevance to a disease under study. This work presents a gene prioritization method based on integrated biological networks that incorporates and models the various levels of relevance and reliability of diverse sources. The method is shown to achieve significantly higher performance as compared to two well-known gene prioritization algorithms. Essentially, no bias in the performance was seen as it was applied to diseases of diverse ethnology, e.g., monogenic, polygenic and cancer. The method was highly stable and robust against significant levels of noise in the data. Biological networks are often sparse, which can impede the operation of associationbased gene prioritization algorithms such as the one presented here from a computational perspective. As a potential approach to overcome this limitation, we explore the value that transcription factor binding sites can have in elucidating suitable targets. Transcription factors are needed for the expression of most genes, especially in higher organisms and hence genes can be associated via their genetic regulatory properties. While each transcription factor recognizes specific DNA sequence patterns, such patterns are mostly unknown for many transcription factors. Even those that are known are inconsistently reported in the literature, implying a potentially high level of inaccuracy. We developed computational methods for prediction and improvement of transcription factor binding patterns. Tests performed on the improvement method by employing synthetic patterns under various conditions showed that the method is very robust and the patterns produced invariably converge to nearly identical series of patterns. Preliminary tests were conducted to incorporate knowledge from transcription factor binding sites into our networkbased model for prioritization, with encouraging results. Genes have widely different pertinences to the etiology and pathology of diseases. Thus, they can be ranked according to their disease-significance on a genomic scale, which is the subject of gene prioritization. Given a set of genes known to be related to a disease, it is reasonable to use them as a basis to determine the significance of other candidate genes, which will then be ranked based on the association they exhibit with respect to the given set of known genes. Experimental and computational data of various kinds have different reliability and relevance to a disease under study. This work presents a gene prioritization method based on integrated biological networks that incorporates and models the various levels of relevance and reliability of diverse sources. The method is shown to achieve significantly higher performance as compared to two well-known gene prioritization algorithms. Essentially, no bias in the performance was seen as it was applied to diseases of diverse ethnology, e.g., monogenic, polygenic and cancer. The method was highly stable and robust against significant levels of noise in the data. Biological networks are often sparse, which can impede the operation of associationbased gene prioritization algorithms such as the one presented here from a computational perspective. As a potential approach to overcome this limitation, we explore the value that transcription factor binding sites can have in elucidating suitable targets. Transcription factors are needed for the expression of most genes, especially in higher organisms and hence genes can be associated via their genetic regulatory properties. While each transcription factor recognizes specific DNA sequence patterns, such patterns are mostly unknown for many transcription factors. Even those that are known are inconsistently reported in the literature, implying a potentially high level of inaccuracy. We developed computational methods for prediction and improvement of transcription factor binding patterns. Tests performed on the improvement method by employing synthetic patterns under various conditions showed that the method is very robust and the patterns produced invariably converge to nearly identical series of patterns. Preliminary tests were conducted to incorporate knowledge from transcription factor binding sites into our networkbased model for prioritization, with encouraging results. To validate these approaches in a disease-specific context, we built a schizophreniaspecific network based on the inferred associations and performed a comprehensive prioritization of human genes with respect to the disease. These results are expected to be validated empirically, but computational validation using known targets are very positive.
ContributorsLee, Jang (Author) / Gonzalez, Graciela (Thesis advisor) / Ye, Jieping (Committee member) / Davulcu, Hasan (Committee member) / Gallitano-Mendel, Amelia (Committee member) / Arizona State University (Publisher)
Created2011
Description
S-Taliro is a fully functional Matlab toolbox that searches for trajectories of minimal robustness in hybrid systems that are implemented as either m-functions or Simulink/State flow models. Trajectories with minimal robustness are found using automatic testing of hybrid systems against user specifications. In this work we use Metric Temporal Logic (MTL) to describe the user specifications for the hybrid systems. We then try to falsify the MTL specification using global minimization of robustness metric. Global minimization is carried out using stochastic optimization algorithms like Monte-Carlo (MC) and Extended Ant Colony Optimization (EACO) algorithms. Irrespective of the type of the model we provide as an input to S-Taliro, the user needs to specify the MTL specification, the initial conditions and the bounds on the inputs. S-Taliro then uses this information to generate test inputs which are used to simulate the system. The simulation trace is then provided as an input to Taliro which computes the robustness estimate of the MTL formula. Global minimization of this robustness metric is performed to generate new test inputs which again generate simulation traces which are closer to falsifying the MTL formula. Traces with negative robustness values indicate that the simulation trace falsified the MTL formula. Traces with positive robustness values are also of great importance because they indicate how robust the system is against the given specification. S-Taliro has been seamlessly integrated into the Matlab environment, which is extensively used for model-based development of control software. Moreover the toolbox has been developed in a modular fashion and therefore adding new optimization algorithms is easy and straightforward. In this work I present the architecture of S-Taliro and its working on a few benchmark problems.
ContributorsAnnapureddy, Yashwanth Singh Rahul (Author) / Fainekos, Georgios (Thesis advisor) / Lee, Yann-Hang (Committee member) / Gupta, Sandeep (Committee member) / Arizona State University (Publisher)
Created2011
Description
Developed a business product with a team of CS students.
ContributorsPerri, Cole Thomas (Co-author) / Hernandez, Maximilliano (Co-author) / Schneider, Kaitlin (Co-author) / Call, Andy (Thesis director) / Hunt, Neil (Committee member) / School of Accountancy (Contributor) / Watts College of Public Service & Community Solut (Contributor) / WPC Graduate Programs (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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
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
Description
A semiconductor supply chain modeling and simulation platform using Linear Program (LP) optimization and parallel Discrete Event System Specification (DEVS) process models has been developed in a joint effort by ASU and Intel Corporation. A Knowledge Interchange Broker (KIBDEVS/LP) was developed to broker information synchronously between the DEVS and LP models. Recently a single-echelon heuristic Inventory Strategy Module (ISM) was added to correct for forecast bias in customer demand data using different smoothing techniques. The optimization model could then use information provided by the forecast model to make better decisions for the process model. The composition of ISM with LP and DEVS models resulted in the first realization of what is now called the Optimization Simulation Forecast (OSF) platform. It could handle a single echelon supply chain system consisting of single hubs and single products In this thesis, this single-echelon simulation platform is extended to handle multiple echelons with multiple inventory elements handling multiple products. The main aspect for the multi-echelon OSF platform was to extend the KIBDEVS/LP such that ISM interactions with the LP and DEVS models could also be supported. To achieve this, a new, scalable XML schema for the KIB has been developed. The XML schema has also resulted in strengthening the KIB execution engine design. A sequential scheme controls the executions of the DEVS-Suite simulator, CPLEX optimizer, and ISM engine. To use the ISM for multiple echelons, it is extended to compute forecast customer demands and safety stocks over multiple hubs and products. Basic examples for semiconductor manufacturing spanning single and two echelon supply chain systems have been developed and analyzed. Experiments using perfect data were conducted to show the correctness of the OSF platform design and implementation. Simple, but realistic experiments have also been conducted. They highlight the kinds of supply chain dynamics that can be evaluated using discrete event process simulation, linear programming optimization, and heuristics forecasting models.
ContributorsSmith, James Melkon (Author) / Sarjoughian, Hessam S. (Thesis advisor) / Davulcu, Hasan (Committee member) / Fainekos, Georgios (Committee member) / Arizona State University (Publisher)
Created2012
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 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
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 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
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
Objective of this thesis project is to build a prototype using Linear Temporal Logic specifications for generating a 2D motion plan commanding an iRobot to fulfill the specifications. This thesis project was created for Cyber Physical Systems Lab in Arizona State University. The end product of this thesis is creation of a software solution which can be used in the academia and industry for research in cyber physical systems related applications. The major features of the project are: creating a modular system for motion planning, use of Robot Operating System (ROS), use of triangulation for environment decomposition and using stargazer sensor for localization. The project is built on an open source software called ROS which provides an environment where it is very easy to integrate different modules be it software or hardware on a Linux based platform. Use of ROS implies the project or its modules can be adapted quickly for different applications as the need arises. The final software package created and tested takes a data file as its input which contains the LTL specifications, a symbols list used in the LTL and finally the environment polygon data containing real world coordinates for all polygons and also information on neighbors and parents of each polygon. The software package successfully ran the experiment of coverage, reachability with avoidance and sequencing.
ContributorsPandya, Parth (Author) / Fainekos, Georgios (Thesis advisor) / Dasgupta, Partha (Committee member) / Lee, Yann-Hang (Committee member) / Arizona State University (Publisher)
Created2013