Matching Items (14)
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- All Subjects: Statistics
- Creators: Zhou, Shuang
- Member of: ASU Electronic Theses and Dissertations
Description
With the increased demand for genetically modified T-cells in treating hematological malignancies, the need for an optimized measurement policy within the current good manufacturing practices for better quality control has grown greatly. There are several steps involved in manufacturing gene therapy. These steps are for the autologous-type gene therapy, in chronological order, are harvesting T-cells from the patient, activation of the cells (thawing the cryogenically frozen cells after transport to manufacturing center), viral vector transduction, Chimeric Antigen Receptor (CAR) attachment during T-cell expansion, then infusion into patient. The need for improved measurement heuristics within the transduction and expansion portions of the manufacturing process has reached an all-time high because of the costly nature of manufacturing the product, the high cycle time (approximately 14-28 days from activation to infusion), and the risk for external contamination during manufacturing that negatively impacts patients post infusion (such as illness and death).
The main objective of this work is to investigate and improve measurement policies on the basis of quality control in the transduction/expansion bio-manufacturing processes. More specifically, this study addresses the issue of measuring yield within the transduction/expansion phases of gene therapy. To do so, it was decided to model the process as a Markov Decision Process where the decisions being made are optimally chosen to create an overall optimal measurement policy; for a set of predefined parameters.
The main objective of this work is to investigate and improve measurement policies on the basis of quality control in the transduction/expansion bio-manufacturing processes. More specifically, this study addresses the issue of measuring yield within the transduction/expansion phases of gene therapy. To do so, it was decided to model the process as a Markov Decision Process where the decisions being made are optimally chosen to create an overall optimal measurement policy; for a set of predefined parameters.
ContributorsStarkey, Michaela (Author) / Pedrielli, Giulia (Thesis advisor) / Li, Jing (Committee member) / Wu, Teresa (Committee member) / Arizona State University (Publisher)
Created2020
Description
Nonalcoholic Steatohepatitis (NASH) is a severe form of Nonalcoholic fatty liverdisease, that is caused due to excessive calorie intake, sedentary lifestyle and in the
absence of severe alcohol consumption. It is widely prevalent in the United States
and in many other developed countries, affecting up to 25 percent of the population.
Due to being asymptotic, it usually goes unnoticed and may lead to liver failure if
not treated at the right time.
Currently, liver biopsy is the gold standard to diagnose NASH, but being an
invasive procedure, it comes with it's own complications along with the inconvenience
of sampling repeated measurements over a period of time. Hence, noninvasive
procedures to assess NASH are urgently required. Magnetic Resonance Elastography
(MRE) based Shear Stiffness and Loss Modulus along with Magnetic Resonance
Imaging based proton density fat fraction have been successfully combined to predict
NASH stages However, their role in the prediction of disease progression still remains
to be investigated.
This thesis thus looks into combining features from serial MRE observations to
develop statistical models to predict NASH progression. It utilizes data from an experiment
conducted on male mice to develop progressive and regressive NASH and
trains ordinal models, ordered probit regression and ordinal forest on labels generated
from a logistic regression model. The models are assessed on histological data collected
at the end point of the experiment. The models developed provide a framework
to utilize a non-invasive tool to predict NASH disease progression.
ContributorsDeshpande, Eeshan (Author) / Ju, Feng (Thesis advisor) / Wu, Teresa (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2021
Description
Spatial regression is one of the central topics in spatial statistics. Based on the goals, interpretation or prediction, spatial regression models can be classified into two categories, linear mixed regression models and nonlinear regression models. This dissertation explored these models and their real world applications. New methods and models were proposed to overcome the challenges in practice. There are three major parts in the dissertation.
In the first part, nonlinear regression models were embedded into a multistage workflow to predict the spatial abundance of reef fish species in the Gulf of Mexico. There were two challenges, zero-inflated data and out of sample prediction. The methods and models in the workflow could effectively handle the zero-inflated sampling data without strong assumptions. Three strategies were proposed to solve the out of sample prediction problem. The results and discussions showed that the nonlinear prediction had the advantages of high accuracy, low bias and well-performed in multi-resolution.
In the second part, a two-stage spatial regression model was proposed for analyzing soil carbon stock (SOC) data. In the first stage, there was a spatial linear mixed model that captured the linear and stationary effects. In the second stage, a generalized additive model was used to explain the nonlinear and nonstationary effects. The results illustrated that the two-stage model had good interpretability in understanding the effect of covariates, meanwhile, it kept high prediction accuracy which is competitive to the popular machine learning models, like, random forest, xgboost and support vector machine.
A new nonlinear regression model, Gaussian process BART (Bayesian additive regression tree), was proposed in the third part. Combining advantages in both BART and Gaussian process, the model could capture the nonlinear effects of both observed and latent covariates. To develop the model, first, the traditional BART was generalized to accommodate correlated errors. Then, the failure of likelihood based Markov chain Monte Carlo (MCMC) in parameter estimating was discussed. Based on the idea of analysis of variation, back comparing and tuning range, were proposed to tackle this failure. Finally, effectiveness of the new model was examined by experiments on both simulation and real data.
In the first part, nonlinear regression models were embedded into a multistage workflow to predict the spatial abundance of reef fish species in the Gulf of Mexico. There were two challenges, zero-inflated data and out of sample prediction. The methods and models in the workflow could effectively handle the zero-inflated sampling data without strong assumptions. Three strategies were proposed to solve the out of sample prediction problem. The results and discussions showed that the nonlinear prediction had the advantages of high accuracy, low bias and well-performed in multi-resolution.
In the second part, a two-stage spatial regression model was proposed for analyzing soil carbon stock (SOC) data. In the first stage, there was a spatial linear mixed model that captured the linear and stationary effects. In the second stage, a generalized additive model was used to explain the nonlinear and nonstationary effects. The results illustrated that the two-stage model had good interpretability in understanding the effect of covariates, meanwhile, it kept high prediction accuracy which is competitive to the popular machine learning models, like, random forest, xgboost and support vector machine.
A new nonlinear regression model, Gaussian process BART (Bayesian additive regression tree), was proposed in the third part. Combining advantages in both BART and Gaussian process, the model could capture the nonlinear effects of both observed and latent covariates. To develop the model, first, the traditional BART was generalized to accommodate correlated errors. Then, the failure of likelihood based Markov chain Monte Carlo (MCMC) in parameter estimating was discussed. Based on the idea of analysis of variation, back comparing and tuning range, were proposed to tackle this failure. Finally, effectiveness of the new model was examined by experiments on both simulation and real data.
ContributorsLu, Xuetao (Author) / McCulloch, Robert (Thesis advisor) / Hahn, Paul (Committee member) / Lan, Shiwei (Committee member) / Zhou, Shuang (Committee member) / Saul, Steven (Committee member) / Arizona State University (Publisher)
Created2020
Description
Buildings consume nearly 50% of the total energy in the United States, which drives the need to develop high-fidelity models for building energy systems. Extensive methods and techniques have been developed, studied, and applied to building energy simulation and forecasting, while most of work have focused on developing dedicated modeling approach for generic buildings. In this study, an integrated computationally efficient and high-fidelity building energy modeling framework is proposed, with the concentration on developing a generalized modeling approach for various types of buildings. First, a number of data-driven simulation models are reviewed and assessed on various types of computationally expensive simulation problems. Motivated by the conclusion that no model outperforms others if amortized over diverse problems, a meta-learning based recommendation system for data-driven simulation modeling is proposed. To test the feasibility of the proposed framework on the building energy system, an extended application of the recommendation system for short-term building energy forecasting is deployed on various buildings. Finally, Kalman filter-based data fusion technique is incorporated into the building recommendation system for on-line energy forecasting. Data fusion enables model calibration to update the state estimation in real-time, which filters out the noise and renders more accurate energy forecast. The framework is composed of two modules: off-line model recommendation module and on-line model calibration module. Specifically, the off-line model recommendation module includes 6 widely used data-driven simulation models, which are ranked by meta-learning recommendation system for off-line energy modeling on a given building scenario. Only a selective set of building physical and operational characteristic features is needed to complete the recommendation task. The on-line calibration module effectively addresses system uncertainties, where data fusion on off-line model is applied based on system identification and Kalman filtering methods. The developed data-driven modeling framework is validated on various genres of buildings, and the experimental results demonstrate desired performance on building energy forecasting in terms of accuracy and computational efficiency. The framework could be easily implemented into building energy model predictive control (MPC), demand response (DR) analysis and real-time operation decision support systems.
ContributorsCui, Can (Author) / Wu, Teresa (Thesis advisor) / Weir, Jeffery D. (Thesis advisor) / Li, Jing (Committee member) / Fowler, John (Committee member) / Hu, Mengqi (Committee member) / Arizona State University (Publisher)
Created2016