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- Member of: ASU Electronic Theses and Dissertations
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
Hepatocellular carcinoma (HCC) is a malignant tumor and seventh most common cancer in human. Every year there is a significant rise in the number of patients suffering from HCC. Most clinical research has focused on HCC early detection so that there are high chances of patient's survival. Emerging advancements in functional and structural imaging techniques have provided the ability to detect microscopic changes in tumor micro environment and micro structure. The prime focus of this thesis is to validate the applicability of advanced imaging modality, Magnetic Resonance Elastography (MRE), for HCC diagnosis. The research was carried out on three HCC patient's data and three sets of experiments were conducted. The main focus was on quantitative aspect of MRE in conjunction with Texture Analysis, an advanced imaging processing pipeline and multi-variate analysis machine learning method for accurate HCC diagnosis. We analyzed the techniques to handle unbalanced data and evaluate the efficacy of sampling techniques. Along with this we studied different machine learning algorithms and developed models using them. Performance metrics such as Prediction Accuracy, Sensitivity and Specificity have been used for evaluation for the final developed model. We were able to identify the significant features in the dataset and also the selected classifier was robust in predicting the response class variable with high accuracy.
ContributorsBansal, Gaurav (Author) / Wu, Teresa (Thesis advisor) / Mitchell, Ross (Thesis advisor) / Li, Jing (Committee member) / Arizona State University (Publisher)
Created2013
Description
A P-value based method is proposed for statistical monitoring of various types of profiles in phase II. The performance of the proposed method is evaluated by the average run length criterion under various shifts in the intercept, slope and error standard deviation of the model. In our proposed approach, P-values are computed at each level within a sample. If at least one of the P-values is less than a pre-specified significance level, the chart signals out-of-control. The primary advantage of our approach is that only one control chart is required to monitor several parameters simultaneously: the intercept, slope(s), and the error standard deviation. A comprehensive comparison of the proposed method and the existing KMW-Shewhart method for monitoring linear profiles is conducted. In addition, the effect that the number of observations within a sample has on the performance of the proposed method is investigated. The proposed method was also compared to the T^2 method discussed in Kang and Albin (2000) for multivariate, polynomial, and nonlinear profiles. A simulation study shows that overall the proposed P-value method performs satisfactorily for different profile types.
ContributorsAdibi, Azadeh (Author) / Montgomery, Douglas C. (Thesis advisor) / Borror, Connie (Thesis advisor) / Li, Jing (Committee member) / Zhang, Muhong (Committee member) / Arizona State University (Publisher)
Created2013
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
In today's global market, companies are facing unprecedented levels of uncertainties in supply, demand and in the economic environment. A critical issue for companies to survive increasing competition is to monitor the changing business environment and manage disturbances and changes in real time. In this dissertation, an integrated framework is proposed using simulation and online calibration methods to enable the adaptive management of large-scale complex supply chain systems. The design, implementation and verification of the integrated approach are studied in this dissertation. The research contributions are two-fold. First, this work enriches symbiotic simulation methodology by proposing a framework of simulation and advanced data fusion methods to improve simulation accuracy. Data fusion techniques optimally calibrate the simulation state/parameters by considering errors in both the simulation models and in measurements of the real-world system. Data fusion methods - Kalman Filtering, Extended Kalman Filtering, and Ensemble Kalman Filtering - are examined and discussed under varied conditions of system chaotic levels, data quality and data availability. Second, the proposed framework is developed, validated and demonstrated in `proof-of-concept' case studies on representative supply chain problems. In the case study of a simplified supply chain system, Kalman Filtering is applied to fuse simulation data and emulation data to effectively improve the accuracy of the detection of abnormalities. In the case study of the `beer game' supply chain model, the system's chaotic level is identified as a key factor to influence simulation performance and the choice of data fusion method. Ensemble Kalman Filtering is found more robust than Extended Kalman Filtering in a highly chaotic system. With appropriate tuning, the improvement of simulation accuracy is up to 80% in a chaotic system, and 60% in a stable system. In the last study, the integrated framework is applied to adaptive inventory control of a multi-echelon supply chain with non-stationary demand. It is worth pointing out that the framework proposed in this dissertation is not only useful in supply chain management, but also suitable to model other complex dynamic systems, such as healthcare delivery systems and energy consumption networks.
ContributorsWang, Shanshan (Author) / Wu, Teresa (Thesis advisor) / Fowler, John (Thesis advisor) / Pfund, Michele (Committee member) / Li, Jing (Committee member) / Pavlicek, William (Committee member) / Arizona State University (Publisher)
Created2010
Description
High-dimensional data is omnipresent in modern industrial systems. An imaging sensor in a manufacturing plant a can take images of millions of pixels or a sensor may collect months of data at very granular time steps. Dimensionality reduction techniques are commonly used for dealing with such data. In addition, outliers typically exist in such data, which may be of direct or indirect interest given the nature of the problem that is being solved. Current research does not address the interdependent nature of dimensionality reduction and outliers. Some works ignore the existence of outliers altogether—which discredits the robustness of these methods in real life—while others provide suboptimal, often band-aid solutions. In this dissertation, I propose novel methods to achieve outlier-awareness in various dimensionality reduction methods. The problem is considered from many different angles depend- ing on the dimensionality reduction technique used (e.g., deep autoencoder, tensors), the nature of the application (e.g., manufacturing, transportation) and the outlier structure (e.g., sparse point anomalies, novelties).
ContributorsSergin, Nurettin Dorukhan (Author) / Yan, Hao (Thesis advisor) / Li, Jing (Committee member) / Wu, Teresa (Committee member) / Tsung, Fugee (Committee member) / Arizona State University (Publisher)
Created2021
Description
Technology advancements in diagnostic imaging, smart sensing, and health information systems have resulted in a data-rich environment in health care, which offers a great opportunity for Precision Medicine. The objective of my research is to develop data fusion and system informatics approaches for quality and performance improvement of health care. In my dissertation, I focus on three emerging problems in health care and develop novel statistical models and machine learning algorithms to tackle these problems from diagnosis to care to system-level decision-making.
The first topic is diagnosis/subtyping of migraine to customize effective treatment to different subtypes of patients. Existing clinical definitions of subtypes use somewhat arbitrary boundaries primarily based on patient self-reported symptoms, which are subjective and error-prone. My research develops a novel Multimodality Factor Mixture Model that discovers subtypes of migraine from multimodality imaging MRI data, which provides complementary accurate measurements of the disease. Patients in the different subtypes show significantly different clinical characteristics of the disease. Treatment tailored and optimized for patients of the same subtype paves the road toward Precision Medicine.
The second topic focuses on coordinated patient care. Care coordination between nurses and with other health care team members is important for providing high-quality and efficient care to patients. The recently developed Nurse Care Coordination Instrument (NCCI) is the first of its kind that enables large-scale quantitative data to be collected. My research develops a novel Multi-response Multi-level Model (M3) that enables transfer learning in NCCI data fusion. M3 identifies key factors that contribute to improving care coordination, and facilitates the design and optimization of nurses’ training, workload assignment, and practice environment, which leads to improved patient outcomes.
The last topic is about system-level decision-making for Alzheimer’s disease early detection at the early stage of Mild Cognitive Impairment (MCI), by predicting each MCI patient’s risk of converting to AD using imaging and proteomic biomarkers. My research proposes a systems engineering approach that integrates the multi-perspectives, including prediction accuracy, biomarker cost/availability, patient heterogeneity and diagnostic efficiency, and allows for system-wide optimized decision regarding the biomarker testing process for prediction of MCI conversion.
The first topic is diagnosis/subtyping of migraine to customize effective treatment to different subtypes of patients. Existing clinical definitions of subtypes use somewhat arbitrary boundaries primarily based on patient self-reported symptoms, which are subjective and error-prone. My research develops a novel Multimodality Factor Mixture Model that discovers subtypes of migraine from multimodality imaging MRI data, which provides complementary accurate measurements of the disease. Patients in the different subtypes show significantly different clinical characteristics of the disease. Treatment tailored and optimized for patients of the same subtype paves the road toward Precision Medicine.
The second topic focuses on coordinated patient care. Care coordination between nurses and with other health care team members is important for providing high-quality and efficient care to patients. The recently developed Nurse Care Coordination Instrument (NCCI) is the first of its kind that enables large-scale quantitative data to be collected. My research develops a novel Multi-response Multi-level Model (M3) that enables transfer learning in NCCI data fusion. M3 identifies key factors that contribute to improving care coordination, and facilitates the design and optimization of nurses’ training, workload assignment, and practice environment, which leads to improved patient outcomes.
The last topic is about system-level decision-making for Alzheimer’s disease early detection at the early stage of Mild Cognitive Impairment (MCI), by predicting each MCI patient’s risk of converting to AD using imaging and proteomic biomarkers. My research proposes a systems engineering approach that integrates the multi-perspectives, including prediction accuracy, biomarker cost/availability, patient heterogeneity and diagnostic efficiency, and allows for system-wide optimized decision regarding the biomarker testing process for prediction of MCI conversion.
ContributorsSi, Bing (Author) / Li, Jing (Thesis advisor) / Montgomery, Douglas C. (Committee member) / Schwedt, Todd (Committee member) / Wu, Teresa (Committee member) / Arizona State University (Publisher)
Created2018
Description
Mathematical modeling and decision-making within the healthcare industry have given means to quantitatively evaluate the impact of decisions into diagnosis, screening, and treatment of diseases. In this work, we look into a specific, yet very important disease, the Alzheimer. In the United States, Alzheimer’s Disease (AD) is the 6th leading cause of death. Diagnosis of AD cannot be confidently confirmed until after death. This has prompted the importance of early diagnosis of AD, based upon symptoms of cognitive decline. A symptom of early cognitive decline and indicator of AD is Mild Cognitive Impairment (MCI). In addition to this qualitative test, Biomarker tests have been proposed in the medical field including p-Tau, FDG-PET, and hippocampal. These tests can be administered to patients as early detectors of AD thus improving patients’ life quality and potentially reducing the costs of the health structure. Preliminary work has been conducted in the development of a Sequential Tree Based Classifier (STC), which helps medical providers predict if a patient will contract AD or not, by sequentially testing these biomarker tests. The STC model, however, has its limitations and the need for a more complex, robust model is needed. In fact, STC assumes a general linear model as the status of the patient based upon the tests results. We take a simulation perspective and try to define a more complex model that represents the patient evolution in time.
Specifically, this thesis focuses on the formulation of a Markov Chain model that is complex and robust. This Markov Chain model emulates the evolution of MCI patients based upon doctor visits and the sequential administration of biomarker tests. Data provided to create this Markov Chain model were collected by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The data lacked detailed information of the sequential administration of the biomarker tests and therefore, different analytical approaches were tried and conducted in order to calibrate the model. The resulting Markov Chain model provided the capability to conduct experiments regarding different parameters of the Markov Chain and yielded different results of patients that contracted AD and those that did not, leading to important insights into effect of thresholds and sequence on patient prediction capability as well as health costs reduction.
The data in this thesis was provided from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). ADNI investigators did not contribute to any analysis or writing of this thesis. A list of the ADNI investigators can be found at: http://adni.loni.usc.edu/about/governance/principal-investigators/ .
Specifically, this thesis focuses on the formulation of a Markov Chain model that is complex and robust. This Markov Chain model emulates the evolution of MCI patients based upon doctor visits and the sequential administration of biomarker tests. Data provided to create this Markov Chain model were collected by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The data lacked detailed information of the sequential administration of the biomarker tests and therefore, different analytical approaches were tried and conducted in order to calibrate the model. The resulting Markov Chain model provided the capability to conduct experiments regarding different parameters of the Markov Chain and yielded different results of patients that contracted AD and those that did not, leading to important insights into effect of thresholds and sequence on patient prediction capability as well as health costs reduction.
The data in this thesis was provided from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). ADNI investigators did not contribute to any analysis or writing of this thesis. A list of the ADNI investigators can be found at: http://adni.loni.usc.edu/about/governance/principal-investigators/ .
ContributorsCamarena, Raquel (Author) / Pedrielli, Giulia (Thesis advisor) / Li, Jing (Thesis advisor) / Wu, Teresa (Committee member) / Arizona State University (Publisher)
Created2018
Description
Semi-supervised learning (SSL) is sub-field of statistical machine learning that is useful for problems that involve having only a few labeled instances with predictor (X) and target (Y) information, and abundance of unlabeled instances that only have predictor (X) information. SSL harnesses the target information available in the limited labeled data, as well as the information in the abundant unlabeled data to build strong predictive models. However, not all the included information is useful. For example, some features may correspond to noise and including them will hurt the predictive model performance. Additionally, some instances may not be as relevant to model building and their inclusion will increase training time and potentially hurt the model performance. The objective of this research is to develop novel SSL models to balance data inclusivity and usability. My dissertation research focuses on applications of SSL in healthcare, driven by problems in brain cancer radiomics, migraine imaging, and Parkinson’s Disease telemonitoring.
The first topic introduces an integration of machine learning (ML) and a mechanistic model (PI) to develop an SSL model applied to predicting cell density of glioblastoma brain cancer using multi-parametric medical images. The proposed ML-PI hybrid model integrates imaging information from unbiopsied regions of the brain as well as underlying biological knowledge from the mechanistic model to predict spatial tumor density in the brain.
The second topic develops a multi-modality imaging-based diagnostic decision support system (MMI-DDS). MMI-DDS consists of modality-wise principal components analysis to incorporate imaging features at different aggregation levels (e.g., voxel-wise, connectivity-based, etc.), a constrained particle swarm optimization (cPSO) feature selection algorithm, and a clinical utility engine that utilizes inverse operators on chosen principal components for white-box classification models.
The final topic develops a new SSL regression model with integrated feature and instance selection called s2SSL (with “s2” referring to selection in two different ways: feature and instance). s2SSL integrates cPSO feature selection and graph-based instance selection to simultaneously choose the optimal features and instances and build accurate models for continuous prediction. s2SSL was applied to smartphone-based telemonitoring of Parkinson’s Disease patients.
The first topic introduces an integration of machine learning (ML) and a mechanistic model (PI) to develop an SSL model applied to predicting cell density of glioblastoma brain cancer using multi-parametric medical images. The proposed ML-PI hybrid model integrates imaging information from unbiopsied regions of the brain as well as underlying biological knowledge from the mechanistic model to predict spatial tumor density in the brain.
The second topic develops a multi-modality imaging-based diagnostic decision support system (MMI-DDS). MMI-DDS consists of modality-wise principal components analysis to incorporate imaging features at different aggregation levels (e.g., voxel-wise, connectivity-based, etc.), a constrained particle swarm optimization (cPSO) feature selection algorithm, and a clinical utility engine that utilizes inverse operators on chosen principal components for white-box classification models.
The final topic develops a new SSL regression model with integrated feature and instance selection called s2SSL (with “s2” referring to selection in two different ways: feature and instance). s2SSL integrates cPSO feature selection and graph-based instance selection to simultaneously choose the optimal features and instances and build accurate models for continuous prediction. s2SSL was applied to smartphone-based telemonitoring of Parkinson’s Disease patients.
ContributorsGaw, Nathan (Author) / Li, Jing (Thesis advisor) / Wu, Teresa (Committee member) / Yan, Hao (Committee member) / Hu, Leland (Committee member) / Arizona State University (Publisher)
Created2019
Description
Transfer learning is a sub-field of statistical modeling and machine learning. It refers to methods that integrate the knowledge of other domains (called source domains) and the data of the target domain in a mathematically rigorous and intelligent way, to develop a better model for the target domain than a model using the data of the target domain alone. While transfer learning is a promising approach in various application domains, my dissertation research focuses on the particular application in health care, including telemonitoring of Parkinson’s Disease (PD) and radiomics for glioblastoma.
The first topic is a Mixed Effects Transfer Learning (METL) model that can flexibly incorporate mixed effects and a general-form covariance matrix to better account for similarity and heterogeneity across subjects. I further develop computationally efficient procedures to handle unknown parameters and large covariance structures. Domain relations, such as domain similarity and domain covariance structure, are automatically quantified in the estimation steps. I demonstrate METL in an application of smartphone-based telemonitoring of PD.
The second topic focuses on an MRI-based transfer learning algorithm for non-invasive surgical guidance of glioblastoma patients. Limited biopsy samples per patient create a challenge to build a patient-specific model for glioblastoma. A transfer learning framework helps to leverage other patient’s knowledge for building a better predictive model. When modeling a target patient, not every patient’s information is helpful. Deciding the subset of other patients from which to transfer information to the modeling of the target patient is an important task to build an accurate predictive model. I define the subset of “transferrable” patients as those who have a positive rCBV-cell density correlation, because a positive correlation is confirmed by imaging theory and the its respective literature.
The last topic is a Privacy-Preserving Positive Transfer Learning (P3TL) model. Although negative transfer has been recognized as an important issue by the transfer learning research community, there is a lack of theoretical studies in evaluating the risk of negative transfer for a transfer learning method and identifying what causes the negative transfer. My work addresses this issue. Driven by the theoretical insights, I extend Bayesian Parameter Transfer (BPT) to a new method, i.e., P3TL. The unique features of P3TL include intelligent selection of patients to transfer in order to avoid negative transfer and maintain patient privacy. These features make P3TL an excellent model for telemonitoring of PD using an At-Home Testing Device.
The first topic is a Mixed Effects Transfer Learning (METL) model that can flexibly incorporate mixed effects and a general-form covariance matrix to better account for similarity and heterogeneity across subjects. I further develop computationally efficient procedures to handle unknown parameters and large covariance structures. Domain relations, such as domain similarity and domain covariance structure, are automatically quantified in the estimation steps. I demonstrate METL in an application of smartphone-based telemonitoring of PD.
The second topic focuses on an MRI-based transfer learning algorithm for non-invasive surgical guidance of glioblastoma patients. Limited biopsy samples per patient create a challenge to build a patient-specific model for glioblastoma. A transfer learning framework helps to leverage other patient’s knowledge for building a better predictive model. When modeling a target patient, not every patient’s information is helpful. Deciding the subset of other patients from which to transfer information to the modeling of the target patient is an important task to build an accurate predictive model. I define the subset of “transferrable” patients as those who have a positive rCBV-cell density correlation, because a positive correlation is confirmed by imaging theory and the its respective literature.
The last topic is a Privacy-Preserving Positive Transfer Learning (P3TL) model. Although negative transfer has been recognized as an important issue by the transfer learning research community, there is a lack of theoretical studies in evaluating the risk of negative transfer for a transfer learning method and identifying what causes the negative transfer. My work addresses this issue. Driven by the theoretical insights, I extend Bayesian Parameter Transfer (BPT) to a new method, i.e., P3TL. The unique features of P3TL include intelligent selection of patients to transfer in order to avoid negative transfer and maintain patient privacy. These features make P3TL an excellent model for telemonitoring of PD using an At-Home Testing Device.
ContributorsYoon, Hyunsoo (Author) / Li, Jing (Thesis advisor) / Wu, Teresa (Committee member) / Yan, Hao (Committee member) / Hu, Leland S. (Committee member) / Arizona State University (Publisher)
Created2018