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- All Subjects: Gene regulatory networks
- Creators: Baral, Chitta
- Resource Type: Text
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
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
Medical records are increasingly being recorded in the form of electronic health records (EHRs), with a significant amount of patient data recorded as unstructured natural language text. Consequently, being able to extract and utilize clinical data present within these records is an important step in furthering clinical care. One important aspect within these records is the presence of prescription information. Existing techniques for extracting prescription information — which includes medication names, dosages, frequencies, reasons for taking, and mode of administration — from unstructured text have focused on the application of rule- and classifier-based methods. While state-of-the-art systems can be effective in extracting many types of information, they require significant effort to develop hand-crafted rules and conduct effective feature engineering. This paper presents the use of a bidirectional LSTM with CRF tagging model initialized with precomputed word embeddings for extracting prescription information from sentences without requiring significant feature engineering. The experimental results, run on the i2b2 2009 dataset, achieve an F1 macro measure of 0.8562, and scores above 0.9449 on four of the six categories, indicating significant potential for this model.
ContributorsRawal, Samarth Chetan (Author) / Baral, Chitta (Thesis director) / Anwar, Saadat (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This thesis concerns the adoption of health information technology in the medical sector, specifically electronic health records (EHRs). EHRs have been seen as a great benefit to the healthcare system and will improve the quality of patient care. The federal government, has seen the benefit EHRs can offer, has been advocating the use and adoption of EHR for nearly a decade now. They have created policies that guide medical providers on how to implement EHRs. However, this thesis concerns the attitudes medical providers in Phoenix have towards government implementation. By interviewing these individuals and cross-referencing their answers with the literature this thesis wants to discover the pitfalls of federal government policy toward EHR implementation and EHR implementation in general. What this thesis found was that there are pitfalls that the federal government has failed to address including loss of provider productivity, lack of interoperability, and workflow improvement. However, the providers do say there is still a place for government to be involved in the implementation of EHR.
ContributorsKaldawi, Nicholas Emad (Author) / Lewis, Paul (Thesis director) / Cortese, Denis (Committee member) / Jones, Ruth (Committee member) / Barrett, The Honors College (Contributor) / School of Politics and Global Studies (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2013-05
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