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- Genre: Masters Thesis
Description
In blindness research, the corpus callosum (CC) is the most frequently studied sub-cortical structure, due to its important involvement in visual processing. While most callosal analyses from brain structural magnetic resonance images (MRI) are limited to the 2D mid-sagittal slice, we propose a novel framework to capture a complete set of 3D morphological differences in the corpus callosum between two groups of subjects. The CCs are segmented from whole brain T1-weighted MRI and modeled as 3D tetrahedral meshes. The callosal surface is divided into superior and inferior patches on which we compute a volumetric harmonic field by solving the Laplace's equation with Dirichlet boundary conditions. We adopt a refined tetrahedral mesh to compute the Laplacian operator, so our computation can achieve sub-voxel accuracy. Thickness is estimated by tracing the streamlines in the harmonic field. We combine areal changes found using surface tensor-based morphometry and thickness information into a vector at each vertex to be used as a metric for the statistical analysis. Group differences are assessed on this combined measure through Hotelling's T2 test. The method is applied to statistically compare three groups consisting of: congenitally blind (CB), late blind (LB; onset > 8 years old) and sighted (SC) subjects. Our results reveal significant differences in several regions of the CC between both blind groups and the sighted groups; and to a lesser extent between the LB and CB groups. These results demonstrate the crucial role of visual deprivation during the developmental period in reshaping the structural architecture of the CC.
ContributorsXu, Liang (Author) / Wang, Yalin (Thesis advisor) / Maciejewski, Ross (Committee member) / Ye, Jieping (Committee member) / Arizona State University (Publisher)
Created2013
Description
Modern, advanced statistical tools from data mining and machine learning have become commonplace in molecular biology in large part because of the “big data” demands of various kinds of “-omics” (e.g., genomics, transcriptomics, metabolomics, etc.). However, in other fields of biology where empirical data sets are conventionally smaller, more traditional statistical methods of inference are still very effective and widely used. Nevertheless, with the decrease in cost of high-performance computing, these fields are starting to employ simulation models to generate insights into questions that have been elusive in the laboratory and field. Although these computational models allow for exquisite control over large numbers of parameters, they also generate data at a qualitatively different scale than most experts in these fields are accustomed to. Thus, more sophisticated methods from big-data statistics have an opportunity to better facilitate the often-forgotten area of bioinformatics that might be called “in-silicomics”.
As a case study, this thesis develops methods for the analysis of large amounts of data generated from a simulated ecosystem designed to understand how mammalian biomechanics interact with environmental complexity to modulate the outcomes of predator–prey interactions. These simulations investigate how other biomechanical parameters relating to the agility of animals in predator–prey pairs are better predictors of pursuit outcomes. Traditional modelling techniques such as forward, backward, and stepwise variable selection are initially used to study these data, but the number of parameters and potentially relevant interaction effects render these methods impractical. Consequently, new modelling techniques such as LASSO regularization are used and compared to the traditional techniques in terms of accuracy and computational complexity. Finally, the splitting rules and instances in the leaves of classification trees provide the basis for future simulation with an economical number of additional runs. In general, this thesis shows the increased utility of these sophisticated statistical techniques with simulated ecological data compared to the approaches traditionally used in these fields. These techniques combined with methods from industrial Design of Experiments will help ecologists extract novel insights from simulations that combine habitat complexity, population structure, and biomechanics.
As a case study, this thesis develops methods for the analysis of large amounts of data generated from a simulated ecosystem designed to understand how mammalian biomechanics interact with environmental complexity to modulate the outcomes of predator–prey interactions. These simulations investigate how other biomechanical parameters relating to the agility of animals in predator–prey pairs are better predictors of pursuit outcomes. Traditional modelling techniques such as forward, backward, and stepwise variable selection are initially used to study these data, but the number of parameters and potentially relevant interaction effects render these methods impractical. Consequently, new modelling techniques such as LASSO regularization are used and compared to the traditional techniques in terms of accuracy and computational complexity. Finally, the splitting rules and instances in the leaves of classification trees provide the basis for future simulation with an economical number of additional runs. In general, this thesis shows the increased utility of these sophisticated statistical techniques with simulated ecological data compared to the approaches traditionally used in these fields. These techniques combined with methods from industrial Design of Experiments will help ecologists extract novel insights from simulations that combine habitat complexity, population structure, and biomechanics.
ContributorsSeto, Christian (Author) / Pavlic, Theodore (Thesis advisor) / Li, Jing (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2018
Description
Proliferation of social media websites and discussion forums in the last decade has resulted in social media mining emerging as an effective mechanism to extract consumer patterns. Most research on social media and pharmacovigilance have concentrated on
Adverse Drug Reaction (ADR) identification. Such methods employ a step of drug search followed by classification of the associated text as consisting an ADR or not. Although this method works efficiently for ADR classifications, if ADR evidence is present in users posts over time, drug mentions fail to capture such ADRs. It also fails to record additional user information which may provide an opportunity to perform an in-depth analysis for lifestyle habits and possible reasons for any medical problems.
Pre-market clinical trials for drugs generally do not include pregnant women, and so their effects on pregnancy outcomes are not discovered early. This thesis presents a thorough, alternative strategy for assessing the safety profiles of drugs during pregnancy by utilizing user timelines from social media. I explore the use of a variety of state-of-the-art social media mining techniques, including rule-based and machine learning techniques, to identify pregnant women, monitor their drug usage patterns, categorize their birth outcomes, and attempt to discover associations between drugs and bad birth outcomes.
The technique used models user timelines as longitudinal patient networks, which provide us with a variety of key information about pregnancy, drug usage, and post-
birth reactions. I evaluate the distinct parts of the pipeline separately, validating the usefulness of each step. The approach to use user timelines in this fashion has produced very encouraging results, and can be employed for a range of other important tasks where users/patients are required to be followed over time to derive population-based measures.
Adverse Drug Reaction (ADR) identification. Such methods employ a step of drug search followed by classification of the associated text as consisting an ADR or not. Although this method works efficiently for ADR classifications, if ADR evidence is present in users posts over time, drug mentions fail to capture such ADRs. It also fails to record additional user information which may provide an opportunity to perform an in-depth analysis for lifestyle habits and possible reasons for any medical problems.
Pre-market clinical trials for drugs generally do not include pregnant women, and so their effects on pregnancy outcomes are not discovered early. This thesis presents a thorough, alternative strategy for assessing the safety profiles of drugs during pregnancy by utilizing user timelines from social media. I explore the use of a variety of state-of-the-art social media mining techniques, including rule-based and machine learning techniques, to identify pregnant women, monitor their drug usage patterns, categorize their birth outcomes, and attempt to discover associations between drugs and bad birth outcomes.
The technique used models user timelines as longitudinal patient networks, which provide us with a variety of key information about pregnancy, drug usage, and post-
birth reactions. I evaluate the distinct parts of the pipeline separately, validating the usefulness of each step. The approach to use user timelines in this fashion has produced very encouraging results, and can be employed for a range of other important tasks where users/patients are required to be followed over time to derive population-based measures.
ContributorsChandrashekar, Pramod Bharadwaj (Author) / Davulcu, Hasan (Thesis advisor) / Gonzalez, Graciela (Thesis advisor) / Hsiao, Sharon (Committee member) / Arizona State University (Publisher)
Created2016
Description
Microbial diversity manifests differently in different ecological niches of the body, with greater diversity generally expected in the gut, given that different locations have unique roles to play in the digestive system. Most microbial research is conducted using fecal samples, meaning the resulting microbes come from various places all throughout the intestines and not specific locations. The Integrative Human Microbiome Project (HMP2), provides a unique opportunity to study microbiomes of both the rectum and ileum through the use of biopsy samples taken from both locations. Using the data provided the microbiome compositions of the rectum and ileum were able to be studied and analyzed to showcase how those microbes associated with clinical variables. Inflammatory bowel diseases are complex diseases that are heterogeneous at clinical, immunological, molecular, genetic, and microbial levels. While it is known that those affected by these diseases have microbiomes that differ from those with healthy guts, not much is known about which changes in the microbiome represent causes rather than effects from changes in health.
ContributorsVecchio, Kurt (Author) / Zhao, Yunpeng (Thesis advisor) / Wang, Yue (Committee member) / Jurutka, Peter (Committee member) / Arizona State University (Publisher)
Created2023
Description
ABSTRACT Genomes are biologically complex entities where an alteration in structure can yield no effect, or have a devastating effect on many pathways. Most of the focus has been on translocations that generate fusion proteins. However, this is only one of many outcomes. Recent work suggests alterations in topologically associated domains (TADs) can lead to changes in gene expression. It is hypothesized that alterations in genome structure can disrupt TADs leading to an alteration in the variability of gene expression within the contained gene expression neighborhood defined by the TAD. To test this hypothesis, variability of gene expression for genes contained within TADs between 37 cancer cell lines from the NCI-60 cell line panel was compared with normal expression data for the corresponding tissues of origin. Those results were correlated with the data on structural events within the NCI-60 cell lines that would disrupt a TAD. It was observed that 2.4% of the TADs displayed altered variance in gene expression when comparing cancer to normal tissue. Using array CGH data from the cancer cell lines to map breakpoints within TADS, it was discovered that altered variance is always associated with a TAD disrupted by a breakpoint, but a breakpoint within a TAD does not always lead to altered variance. TADs with altered variance in gene expression were no different in size than those without altered variance. There is evidence of recurrent pan-cancer alteration in variance for eleven genes within two TADs on two chromosomes (Chromosome 10 & 19) for all 37 cell lines. The genes located within these TADs are enriched in pathways related to RNA processing. This study supports altered variance as a signal of a breakpoint with a functional consequence.
ContributorsDunham, Jocelen Michaela (Author) / Kanthaswamy, Sreethan (Thesis advisor) / Mancenido, Michelle (Thesis advisor) / Bussey, Kimberly J. (Committee member) / Arizona State University (Publisher)
Created2022