Matching Items (19)
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- All Subjects: Bioinformatics
- All Subjects: Machine Learning
- Creators: Runger, George C.
- Status: Published
Description
With the increase in computing power and availability of data, there has never been a greater need to understand data and make decisions from it. Traditional statistical techniques may not be adequate to handle the size of today's data or the complexities of the information hidden within the data. Thus knowledge discovery by machine learning techniques is necessary if we want to better understand information from data. In this dissertation, we explore the topics of asymmetric loss and asymmetric data in machine learning and propose new algorithms as solutions to some of the problems in these topics. We also studied variable selection of matched data sets and proposed a solution when there is non-linearity in the matched data. The research is divided into three parts. The first part addresses the problem of asymmetric loss. A proposed asymmetric support vector machine (aSVM) is used to predict specific classes with high accuracy. aSVM was shown to produce higher precision than a regular SVM. The second part addresses asymmetric data sets where variables are only predictive for a subset of the predictor classes. Asymmetric Random Forest (ARF) was proposed to detect these kinds of variables. The third part explores variable selection for matched data sets. Matched Random Forest (MRF) was proposed to find variables that are able to distinguish case and control without the restrictions that exists in linear models. MRF detects variables that are able to distinguish case and control even in the presence of interaction and qualitative variables.
ContributorsKoh, Derek (Author) / Runger, George C. (Thesis advisor) / Wu, Tong (Committee member) / Pan, Rong (Committee member) / Cesta, John (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
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
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 rate of progress in improving survival of patients with solid tumors is slow due to late stage diagnosis and poor tumor characterization processes that fail to effectively reflect the nature of tumor before treatment or the subsequent change in its dynamics because of treatment. Further advancement of targeted therapies relies on advancements in biomarker research. In the context of solid tumors, bio-specimen samples such as biopsies serve as the main source of biomarkers used in the treatment and monitoring of cancer, even though biopsy samples are susceptible to sampling error and more importantly, are local and offer a narrow temporal scope.
Because of its established role in cancer care and its non-invasive nature imaging offers the potential to complement the findings of cancer biology. Over the past decade, a compelling body of literature has emerged suggesting a more pivotal role for imaging in the diagnosis, prognosis, and monitoring of diseases. These advances have facilitated the rise of an emerging practice known as Radiomics: the extraction and analysis of large numbers of quantitative features from medical images to improve disease characterization and prediction of outcome. It has been suggested that radiomics can contribute to biomarker discovery by detecting imaging traits that are complementary or interchangeable with other markers.
This thesis seeks further advancement of imaging biomarker discovery. This research unfolds over two aims: I) developing a comprehensive methodological pipeline for converting diagnostic imaging data into mineable sources of information, and II) investigating the utility of imaging data in clinical diagnostic applications. Four validation studies were conducted using the radiomics pipeline developed in aim I. These studies had the following goals: (1 distinguishing between benign and malignant head and neck lesions (2) differentiating benign and malignant breast cancers, (3) predicting the status of Human Papillomavirus in head and neck cancers, and (4) predicting neuropsychological performances as they relate to Alzheimer’s disease progression. The long-term objective of this thesis is to improve patient outcome and survival by facilitating incorporation of routine care imaging data into decision making processes.
Because of its established role in cancer care and its non-invasive nature imaging offers the potential to complement the findings of cancer biology. Over the past decade, a compelling body of literature has emerged suggesting a more pivotal role for imaging in the diagnosis, prognosis, and monitoring of diseases. These advances have facilitated the rise of an emerging practice known as Radiomics: the extraction and analysis of large numbers of quantitative features from medical images to improve disease characterization and prediction of outcome. It has been suggested that radiomics can contribute to biomarker discovery by detecting imaging traits that are complementary or interchangeable with other markers.
This thesis seeks further advancement of imaging biomarker discovery. This research unfolds over two aims: I) developing a comprehensive methodological pipeline for converting diagnostic imaging data into mineable sources of information, and II) investigating the utility of imaging data in clinical diagnostic applications. Four validation studies were conducted using the radiomics pipeline developed in aim I. These studies had the following goals: (1 distinguishing between benign and malignant head and neck lesions (2) differentiating benign and malignant breast cancers, (3) predicting the status of Human Papillomavirus in head and neck cancers, and (4) predicting neuropsychological performances as they relate to Alzheimer’s disease progression. The long-term objective of this thesis is to improve patient outcome and survival by facilitating incorporation of routine care imaging data into decision making processes.
ContributorsRanjbar, Sara (Author) / Kaufman, David (Thesis advisor) / Mitchell, Joseph R. (Thesis advisor) / Runger, George C. (Committee member) / Arizona State University (Publisher)
Created2017
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
Description
The data explosion in the past decade is in part due to the widespread use of rich sensors that measure various physical phenomenon -- gyroscopes that measure orientation in phones and fitness devices, the Microsoft Kinect which measures depth information, etc. A typical application requires inferring the underlying physical phenomenon from data, which is done using machine learning. A fundamental assumption in training models is that the data is Euclidean, i.e. the metric is the standard Euclidean distance governed by the L-2 norm. However in many cases this assumption is violated, when the data lies on non Euclidean spaces such as Riemannian manifolds. While the underlying geometry accounts for the non-linearity, accurate analysis of human activity also requires temporal information to be taken into account. Human movement has a natural interpretation as a trajectory on the underlying feature manifold, as it evolves smoothly in time. A commonly occurring theme in many emerging problems is the need to \emph{represent, compare, and manipulate} such trajectories in a manner that respects the geometric constraints. This dissertation is a comprehensive treatise on modeling Riemannian trajectories to understand and exploit their statistical and dynamical properties. Such properties allow us to formulate novel representations for Riemannian trajectories. For example, the physical constraints on human movement are rarely considered, which results in an unnecessarily large space of features, making search, classification and other applications more complicated. Exploiting statistical properties can help us understand the \emph{true} space of such trajectories. In applications such as stroke rehabilitation where there is a need to differentiate between very similar kinds of movement, dynamical properties can be much more effective. In this regard, we propose a generalization to the Lyapunov exponent to Riemannian manifolds and show its effectiveness for human activity analysis. The theory developed in this thesis naturally leads to several benefits in areas such as data mining, compression, dimensionality reduction, classification, and regression.
ContributorsAnirudh, Rushil (Author) / Turaga, Pavan (Thesis advisor) / Cochran, Douglas (Committee member) / Runger, George C. (Committee member) / Taylor, Thomas (Committee member) / Arizona State University (Publisher)
Created2016
Description
Feature learning and the discovery of nonlinear variation patterns in high-dimensional data is an important task in many problem domains, such as imaging, streaming data from sensors, and manufacturing. This dissertation presents several methods for learning and visualizing nonlinear variation in high-dimensional data. First, an automated method for discovering nonlinear variation patterns using deep learning autoencoders is proposed. The approach provides a functional mapping from a low-dimensional representation to the original spatially-dense data that is both interpretable and efficient with respect to preserving information. Experimental results indicate that deep learning autoencoders outperform manifold learning and principal component analysis in reproducing the original data from the learned variation sources.
A key issue in using autoencoders for nonlinear variation pattern discovery is to encourage the learning of solutions where each feature represents a unique variation source, which we define as distinct features. This problem of learning distinct features is also referred to as disentangling factors of variation in the representation learning literature. The remainder of this dissertation highlights and provides solutions for this important problem.
An alternating autoencoder training method is presented and a new measure motivated by orthogonal loadings in linear models is proposed to quantify feature distinctness in the nonlinear models. Simulated point cloud data and handwritten digit images illustrate that standard training methods for autoencoders consistently mix the true variation sources in the learned low-dimensional representation, whereas the alternating method produces solutions with more distinct patterns.
Finally, a new regularization method for learning distinct nonlinear features using autoencoders is proposed. Motivated in-part by the properties of linear solutions, a series of learning constraints are implemented via regularization penalties during stochastic gradient descent training. These include the orthogonality of tangent vectors to the manifold, the correlation between learned features, and the distributions of the learned features. This regularized learning approach yields low-dimensional representations which can be better interpreted and used to identify the true sources of variation impacting a high-dimensional feature space. Experimental results demonstrate the effectiveness of this method for nonlinear variation pattern discovery on both simulated and real data sets.
A key issue in using autoencoders for nonlinear variation pattern discovery is to encourage the learning of solutions where each feature represents a unique variation source, which we define as distinct features. This problem of learning distinct features is also referred to as disentangling factors of variation in the representation learning literature. The remainder of this dissertation highlights and provides solutions for this important problem.
An alternating autoencoder training method is presented and a new measure motivated by orthogonal loadings in linear models is proposed to quantify feature distinctness in the nonlinear models. Simulated point cloud data and handwritten digit images illustrate that standard training methods for autoencoders consistently mix the true variation sources in the learned low-dimensional representation, whereas the alternating method produces solutions with more distinct patterns.
Finally, a new regularization method for learning distinct nonlinear features using autoencoders is proposed. Motivated in-part by the properties of linear solutions, a series of learning constraints are implemented via regularization penalties during stochastic gradient descent training. These include the orthogonality of tangent vectors to the manifold, the correlation between learned features, and the distributions of the learned features. This regularized learning approach yields low-dimensional representations which can be better interpreted and used to identify the true sources of variation impacting a high-dimensional feature space. Experimental results demonstrate the effectiveness of this method for nonlinear variation pattern discovery on both simulated and real data sets.
ContributorsHoward, Phillip (Author) / Runger, George C. (Thesis advisor) / Montgomery, Douglas C. (Committee member) / Mirchandani, Pitu (Committee member) / Apley, Daniel (Committee member) / Arizona State University (Publisher)
Created2016