Matching Items (18)
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- All Subjects: Bioinformatics
- Creators: Kusumi, Kenro
- Creators: Runger, George C.
- Creators: Kim, Seungchan
- Status: Published
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
Vertebrate genomes demonstrate a remarkable range of sizes from 0.3 to 133 gigabase pairs. The proliferation of repeat elements are a major genomic expansion. In particular, long interspersed nuclear elements (LINES) are autonomous retrotransposons that have the ability to "cut and paste" themselves into a host genome through a mechanism called target-primed reverse transcription. LINES have been called "junk DNA," "viral DNA," and "selfish" DNA, and were once thought to be parasitic elements. However, LINES, which diversified before the emergence of many early vertebrates, has strongly shaped the evolution of eukaryotic genomes. This thesis will evaluate LINE abundance, diversity and activity in four anole lizards. An intrageneric analysis will be conducted using comparative phylogenetics and bioinformatics. Comparisons within the Anolis genus, which derives from a single lineage of an adaptive radiation, will be conducted to explore the relationship between LINE retrotransposon activity and causal changes in genomic size and composition.
ContributorsMay, Catherine (Author) / Kusumi, Kenro (Thesis advisor) / Gadau, Juergen (Committee member) / Rawls, Jeffery A (Committee member) / Arizona State University (Publisher)
Created2013
Description
Telomerase enzyme is a truly remarkable enzyme specialized for the addition of short, highly repetitive DNA sequences onto linear eukaryotic chromosome ends. The telomerase enzyme functions as a ribonucleoprotein, minimally composed of the highly conserved catalytic telomerase reverse transcriptase and essential telomerase RNA component containing an internalized short template region within the vastly larger non-coding RNA. Even among closely related groups of species, telomerase RNA is astonishingly divergent in sequence, length, and secondary structure. This massive disparity is highly prohibitive for telomerase RNA identification from previously unexplored groups of species, which is fundamental for secondary structure determination. Combined biochemical enrichment and computational screening methods were employed for the discovery of numerous telomerase RNAs from the poorly characterized echinoderm lineage. This resulted in the revelation that--while closely related to the vertebrate lineage and grossly resembling vertebrate telomerase RNA--the echinoderm telomerase RNA central domain varies extensively in structure and sequence, diverging even within echinoderms amongst sea urchins and brittle stars. Furthermore, the origins of telomerase RNA within the eukaryotic lineage have remained a persistent mystery. The ancient Trypanosoma telomerase RNA was previously identified, however, a functionally verified secondary structure remained elusive. Synthetic Trypanosoma telomerase was generated for molecular dissection of Trypanosoma telomerase RNA revealing two RNA domains functionally equivalent to those found in known telomerase RNAs, yet structurally distinct. This work demonstrates that telomerase RNA is uncommonly divergent in gross architecture, while retaining critical universal elements.
ContributorsPodlevsky, Joshua (Author) / Chen, Julian (Thesis advisor) / Mangone, Marco (Committee member) / Kusumi, Kenro (Committee member) / Wilson-Rawls, Norma (Committee member) / Arizona State University (Publisher)
Created2015
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
The technology expansion seen in the last decade for genomics research has permitted the generation of large-scale data sources pertaining to molecular biological assays, genomics, proteomics, transcriptomics and other modern omics catalogs. New methods to analyze, integrate and visualize these data types are essential to unveil relevant disease mechanisms. Towards these objectives, this research focuses on data integration within two scenarios: (1) transcriptomic, proteomic and functional information and (2) real-time sensor-based measurements motivated by single-cell technology. To assess relationships between protein abundance, transcriptomic and functional data, a nonlinear model was explored at static and temporal levels. The successful integration of these heterogeneous data sources through the stochastic gradient boosted tree approach and its improved predictability are some highlights of this work. Through the development of an innovative validation subroutine based on a permutation approach and the use of external information (i.e., operons), lack of a priori knowledge for undetected proteins was overcome. The integrative methodologies allowed for the identification of undetected proteins for Desulfovibrio vulgaris and Shewanella oneidensis for further biological exploration in laboratories towards finding functional relationships. In an effort to better understand diseases such as cancer at different developmental stages, the Microscale Life Science Center headquartered at the Arizona State University is pursuing single-cell studies by developing novel technologies. This research arranged and applied a statistical framework that tackled the following challenges: random noise, heterogeneous dynamic systems with multiple states, and understanding cell behavior within and across different Barrett's esophageal epithelial cell lines using oxygen consumption curves. These curves were characterized with good empirical fit using nonlinear models with simple structures which allowed extraction of a large number of features. Application of a supervised classification model to these features and the integration of experimental factors allowed for identification of subtle patterns among different cell types visualized through multidimensional scaling. Motivated by the challenges of analyzing real-time measurements, we further explored a unique two-dimensional representation of multiple time series using a wavelet approach which showcased promising results towards less complex approximations. Also, the benefits of external information were explored to improve the image representation.
ContributorsTorres Garcia, Wandaliz (Author) / Meldrum, Deirdre R. (Thesis advisor) / Runger, George C. (Thesis advisor) / Gel, Esma S. (Committee member) / Li, Jing (Committee member) / Zhang, Weiwen (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
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
Rapid advance in sensor and information technology has resulted in both spatially and temporally data-rich environment, which creates a pressing need for us to develop novel statistical methods and the associated computational tools to extract intelligent knowledge and informative patterns from these massive datasets. The statistical challenges for addressing these massive datasets lay in their complex structures, such as high-dimensionality, hierarchy, multi-modality, heterogeneity and data uncertainty. Besides the statistical challenges, the associated computational approaches are also considered essential in achieving efficiency, effectiveness, as well as the numerical stability in practice. On the other hand, some recent developments in statistics and machine learning, such as sparse learning, transfer learning, and some traditional methodologies which still hold potential, such as multi-level models, all shed lights on addressing these complex datasets in a statistically powerful and computationally efficient way. In this dissertation, we identify four kinds of general complex datasets, including "high-dimensional datasets", "hierarchically-structured datasets", "multimodality datasets" and "data uncertainties", which are ubiquitous in many domains, such as biology, medicine, neuroscience, health care delivery, manufacturing, etc. We depict the development of novel statistical models to analyze complex datasets which fall under these four categories, and we show how these models can be applied to some real-world applications, such as Alzheimer's disease research, nursing care process, and manufacturing.
ContributorsHuang, Shuai (Author) / Li, Jing (Thesis advisor) / Askin, Ronald (Committee member) / Ye, Jieping (Committee member) / Runger, George C. (Committee member) / Arizona State University (Publisher)
Created2012
Description
The recent technological advances enable the collection of various complex, heterogeneous and high-dimensional data in biomedical domains. The increasing availability of the high-dimensional biomedical data creates the needs of new machine learning models for effective data analysis and knowledge discovery. This dissertation introduces several unsupervised and supervised methods to help understand the data, discover the patterns and improve the decision making. All the proposed methods can generalize to other industrial fields.
The first topic of this dissertation focuses on the data clustering. Data clustering is often the first step for analyzing a dataset without the label information. Clustering high-dimensional data with mixed categorical and numeric attributes remains a challenging, yet important task. A clustering algorithm based on tree ensembles, CRAFTER, is proposed to tackle this task in a scalable manner.
The second part of this dissertation aims to develop data representation methods for genome sequencing data, a special type of high-dimensional data in the biomedical domain. The proposed data representation method, Bag-of-Segments, can summarize the key characteristics of the genome sequence into a small number of features with good interpretability.
The third part of this dissertation introduces an end-to-end deep neural network model, GCRNN, for time series classification with emphasis on both the accuracy and the interpretation. GCRNN contains a convolutional network component to extract high-level features, and a recurrent network component to enhance the modeling of the temporal characteristics. A feed-forward fully connected network with the sparse group lasso regularization is used to generate the final classification and provide good interpretability.
The last topic centers around the dimensionality reduction methods for time series data. A good dimensionality reduction method is important for the storage, decision making and pattern visualization for time series data. The CRNN autoencoder is proposed to not only achieve low reconstruction error, but also generate discriminative features. A variational version of this autoencoder has great potential for applications such as anomaly detection and process control.
The first topic of this dissertation focuses on the data clustering. Data clustering is often the first step for analyzing a dataset without the label information. Clustering high-dimensional data with mixed categorical and numeric attributes remains a challenging, yet important task. A clustering algorithm based on tree ensembles, CRAFTER, is proposed to tackle this task in a scalable manner.
The second part of this dissertation aims to develop data representation methods for genome sequencing data, a special type of high-dimensional data in the biomedical domain. The proposed data representation method, Bag-of-Segments, can summarize the key characteristics of the genome sequence into a small number of features with good interpretability.
The third part of this dissertation introduces an end-to-end deep neural network model, GCRNN, for time series classification with emphasis on both the accuracy and the interpretation. GCRNN contains a convolutional network component to extract high-level features, and a recurrent network component to enhance the modeling of the temporal characteristics. A feed-forward fully connected network with the sparse group lasso regularization is used to generate the final classification and provide good interpretability.
The last topic centers around the dimensionality reduction methods for time series data. A good dimensionality reduction method is important for the storage, decision making and pattern visualization for time series data. The CRNN autoencoder is proposed to not only achieve low reconstruction error, but also generate discriminative features. A variational version of this autoencoder has great potential for applications such as anomaly detection and process control.
ContributorsLin, Sangdi (Author) / Runger, George C. (Thesis advisor) / Kocher, Jean-Pierre A (Committee member) / Pan, Rong (Committee member) / Escobedo, Adolfo R. (Committee member) / Arizona State University (Publisher)
Created2018
Description
Damage to the central nervous system due to spinal cord or traumatic brain injury, as well as degenerative musculoskeletal disorders such as arthritis, drastically impact the quality of life. Regeneration of complex structures is quite limited in mammals, though other vertebrates possess this ability. Lizards are the most closely related organism to humans that can regenerate de novo skeletal muscle, hyaline cartilage, spinal cord, vasculature, and skin. Progress in studying the cellular and molecular mechanisms of lizard regeneration has previously been limited by a lack of genomic resources. Building on the release of the genome of the green anole, Anolis carolinensis, we developed a second generation, robust RNA-Seq-based genome annotation, and performed the first transcriptomic analysis of tail regeneration in this species. In order to investigate gene expression in regenerating tissue, we performed whole transcriptome and microRNA transcriptome analysis of regenerating tail tip and base and associated tissues, identifying key genetic targets in the regenerative process. These studies have identified components of a genetic program for regeneration in the lizard that includes both developmental and adult repair mechanisms shared with mammals, indicating value in the translation of these findings to future regenerative therapies.
ContributorsHutchins, Elizabeth (Author) / Kusumi, Kenro (Thesis advisor) / Rawls, Jeffrey A. (Committee member) / Denardo, Dale F. (Committee member) / Huentelman, Matthew J. (Committee member) / Arizona State University (Publisher)
Created2015