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- Genre: Academic theses
Description
High throughput transcriptome data analysis like Single-cell Ribonucleic Acid sequencing (scRNA-seq) and Circular Ribonucleic Acid (circRNA) data have made significant breakthroughs, especially in cancer genomics. Analysis of transcriptome time series data is core in identifying time point(s) where drastic changes in gene transcription are associated with homeostatic to non-homeostatic cellular transition (tipping points). In Chapter 2 of this dissertation, I present a novel cell-type specific and co-expression-based tipping point detection method to identify target gene (TG) versus transcription factor (TF) pairs whose differential co-expression across time points drive biological changes in different cell types and the time point when these changes are observed. This method was applied to scRNA-seq data sets from a SARS-CoV-2 study (18 time points), a human cerebellum development study (9 time points), and a lung injury study (18 time points). Similarly, leveraging transcriptome data across treatment time points, I developed methodologies to identify treatment-induced and cell-type specific differentially co-expressed pairs (DCEPs). In part one of Chapter 3, I presented a pipeline that used a series of statistical tests to detect DCEPs. This method was applied to scRNA-seq data of patients with non-small cell lung cancer (NSCLC) sequenced across cancer treatment times. However, this pipeline does not account for correlations among multiple single cells from the same sample and correlations among multiple samples from the same patient. In Part 2 of Chapter 3, I presented a solution to this problem using a mixed-effect model. In Chapter 4, I present a summary of my work that focused on the cross-species analysis of circRNA transcriptome time series data. I compared circRNA profiles in neonatal pig and mouse hearts, identified orthologous circRNAs, and discussed regulation mechanisms of cardiomyocyte proliferation and myocardial regeneration conserved between mouse and pig at different time points.
ContributorsNyarige, Verah Mocheche (Author) / Liu, Li (Thesis advisor) / Wang, Junwen (Thesis advisor) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2022
Description
Beta-Amyloid(Aβ) plaques and tau protein tangles in the brain are now widely recognized as the defining hallmarks of Alzheimer’s disease (AD), followed by structural atrophy detectable on brain magnetic resonance imaging (MRI) scans. However, current methods to detect Aβ/tau pathology are either invasive (lumbar puncture) or quite costly and not widely available (positron emission tomography (PET)). And one of the particular neurodegenerative regions is the hippocampus to which the influence of Aβ/tau on has been one of the research projects focuses in the AD pathophysiological progress.
In this dissertation, I proposed three novel machine learning and statistical models to examine subtle aspects of the hippocampal morphometry from MRI that are associated with Aβ /tau burden in the brain, measured using PET images. The first model is a novel unsupervised feature reduction model to generate a low-dimensional representation of hippocampal morphometry for each individual subject, which has superior performance in predicting Aβ/tau burden in the brain. The second one is an efficient federated group lasso model to identify the hippocampal subregions where atrophy is strongly associated with abnormal Aβ/Tau. The last one is a federated model for imaging genetics, which can identify genetic and transcriptomic influences on hippocampal morphometry. Finally, I stated the results of these three models that have been published or submitted to peer-reviewed conferences and journals.
ContributorsWu, Jianfeng (Author) / Wang, Yalin (Thesis advisor) / Li, Baoxin (Committee member) / Liang, Jianming (Committee member) / Wang, Junwen (Committee member) / Wu, Teresa (Committee member) / Arizona State University (Publisher)
Created2022
Description
Energy use within urban building stocks is continuing to increase globally as populations expand and access to electricity improves. This projected increase in demand could require deployment of new generation capacity, but there is potential to offset some of this demand through modification of the buildings themselves. Building stocks are quasi-permanent infrastructures which have enduring influence on urban energy consumption, and research is needed to understand: 1) how development patterns constrain energy use decisions and 2) how cities can achieve energy and environmental goals given the constraints of the stock. This requires a thorough evaluation of both the growth of the stock and as well as the spatial distribution of use throughout the city. In this dissertation, a case study in Los Angeles County, California (LAC) is used to quantify urban growth, forecast future energy use under climate change, and to make recommendations for mitigating energy consumption increases. A reproducible methodological framework is included for application to other urban areas.
In LAC, residential electricity demand could increase as much as 55-68% between 2020 and 2060, and building technology lock-in has constricted the options for mitigating energy demand, as major changes to the building stock itself are not possible, as only a small portion of the stock is turned over every year. Aggressive and timely efficiency upgrades to residential appliances and building thermal shells can significantly offset the projected increases, potentially avoiding installation of new generation capacity, but regulations on new construction will likely be ineffectual due to the long residence time of the stock (60+ years and increasing). These findings can be extrapolated to other U.S. cities where the majority of urban expansion has already occurred, such as the older cities on the eastern coast. U.S. population is projected to increase 40% by 2060, with growth occurring in the warmer southern and western regions. In these growing cities, improving new construction buildings can help offset electricity demand increases before the city reaches the lock-in phase.
In LAC, residential electricity demand could increase as much as 55-68% between 2020 and 2060, and building technology lock-in has constricted the options for mitigating energy demand, as major changes to the building stock itself are not possible, as only a small portion of the stock is turned over every year. Aggressive and timely efficiency upgrades to residential appliances and building thermal shells can significantly offset the projected increases, potentially avoiding installation of new generation capacity, but regulations on new construction will likely be ineffectual due to the long residence time of the stock (60+ years and increasing). These findings can be extrapolated to other U.S. cities where the majority of urban expansion has already occurred, such as the older cities on the eastern coast. U.S. population is projected to increase 40% by 2060, with growth occurring in the warmer southern and western regions. In these growing cities, improving new construction buildings can help offset electricity demand increases before the city reaches the lock-in phase.
ContributorsReyna, Janet Lorel (Author) / Chester, Mikhail V (Thesis advisor) / Gurney, Kevin (Committee member) / Reddy, T. Agami (Committee member) / Rey, Sergio (Committee member) / Arizona State University (Publisher)
Created2016
Description
This dissertation presents three novel algorithms with real-world applications to genomic oncology. While the methodologies presented here were all developed to overcome various challenges associated with the adoption of high throughput genomic data in clinical oncology, they can be used in other domains as well. First, a network informed feature ranking algorithm is presented, which shows a significant increase in ability to select true predictive features from simulated data sets when compared to other state of the art graphical feature ranking methods. The methodology also shows an increased ability to predict pathological complete response to preoperative chemotherapy from genomic sequencing data of breast cancer patients utilizing domain knowledge from protein-protein interaction networks.
Second, an algorithm that overcomes population biases inherent in the use of a human reference genome developed primarily from European populations is presented to classify microsatellite instability (MSI) status from next-generation-sequencing (NGS) data. The methodology significantly increases the accuracy of MSI status prediction in African and African American ancestries.
Finally, a single variable model is presented to capture the bimodality inherent in genomic data stemming from heterogeneous diseases. This model shows improvements over other parametric models in the measurements of receiver-operator characteristic (ROC) curves for bimodal data. The model is used to estimate ROC curves for heterogeneous biomarkers in a dataset containing breast cancer and cancer-free specimen.
ContributorsSaul, Michelle (Author) / Dinu, Valentin (Thesis advisor) / Liu, Li (Committee member) / Wang, Junwen (Committee member) / Arizona State University (Publisher)
Created2021
Description
Fossil fuel CO2 (FFCO2) emissions are recognized as the dominant greenhouse gas driving climate change (Enting et. al., 1995; Conway et al., 1994; Francey et al., 1995; Bousquet et. al., 1999). Transportation is a major component of FFCO2 emissions, especially in urban areas. An improved understanding of on-road FFCO2 emission at high spatial resolution is essential to both carbon science and mitigation policy. Though considerable research has been accomplished within a few high-income portions of the planet such as the United States and Western Europe, little work has attempted to comprehensively quantify high-resolution on-road FFCO2 emissions globally. Key questions for such a global quantification are: (1) What are the driving factors for on-road FFCO2 emissions? (2) How robust are the relationships? and (3) How do on-road FFCO2 emissions vary with urban form at fine spatial scales?
This study used urban form/socio-economic data combined with self-reported on-road FFCO2 emissions for a sample of global cities to estimate relationships within a multivariate regression framework based on an adjusted STIRPAT model. The on-road high-resolution (whole-city) regression FFCO2 model robustness was evaluated by introducing artificial error, conducting cross-validation, and assessing relationship sensitivity under various model specifications. Results indicated that fuel economy, vehicle ownership, road density and population density were statistically significant factors that correlate with on-road FFCO2 emissions. Of these four variables, fuel economy and vehicle ownership had the most robust relationships.
A second regression model was constructed to examine the relationship between global on-road FFCO2 emissions and urban form factors (described by population
ii
density, road density, and distance to activity centers) at sub-city spatial scales (1 km2). Results showed that: 1) Road density is the most significant (p<2.66e-037) predictor of on-road FFCO2 emissions at the 1 km2 spatial scale; 2) The correlation between population density and on-road FFCO2 emissions for interstates/freeways varies little by city type. For arterials, on-road FFCO2 emissions show a stronger relationship to population density in clustered cities (slope = 0.24) than dispersed cities (slope = 0.13). FFCO2 3) The distance to activity centers has a significant positive relationship with on-road FFCO2 emission for the interstate and freeway toad types, but an insignificant relationship with the arterial road type.
This study used urban form/socio-economic data combined with self-reported on-road FFCO2 emissions for a sample of global cities to estimate relationships within a multivariate regression framework based on an adjusted STIRPAT model. The on-road high-resolution (whole-city) regression FFCO2 model robustness was evaluated by introducing artificial error, conducting cross-validation, and assessing relationship sensitivity under various model specifications. Results indicated that fuel economy, vehicle ownership, road density and population density were statistically significant factors that correlate with on-road FFCO2 emissions. Of these four variables, fuel economy and vehicle ownership had the most robust relationships.
A second regression model was constructed to examine the relationship between global on-road FFCO2 emissions and urban form factors (described by population
ii
density, road density, and distance to activity centers) at sub-city spatial scales (1 km2). Results showed that: 1) Road density is the most significant (p<2.66e-037) predictor of on-road FFCO2 emissions at the 1 km2 spatial scale; 2) The correlation between population density and on-road FFCO2 emissions for interstates/freeways varies little by city type. For arterials, on-road FFCO2 emissions show a stronger relationship to population density in clustered cities (slope = 0.24) than dispersed cities (slope = 0.13). FFCO2 3) The distance to activity centers has a significant positive relationship with on-road FFCO2 emission for the interstate and freeway toad types, but an insignificant relationship with the arterial road type.
ContributorsSong, Yang (Author) / Gurney, Kevin (Thesis advisor) / Kuby, Michael (Committee member) / Golub, Aaron (Committee member) / Chester, Mikhail (Committee member) / Selover, Nancy (Committee member) / Arizona State University (Publisher)
Created2018