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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

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
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Description
Discriminative learning when training and test data belong to different distributions is a challenging and complex task. Often times we have very few or no labeled data from the test or target distribution, but we may have plenty of labeled data from one or multiple related sources with different distributions.

Discriminative learning when training and test data belong to different distributions is a challenging and complex task. Often times we have very few or no labeled data from the test or target distribution, but we may have plenty of labeled data from one or multiple related sources with different distributions. Due to its capability of migrating knowledge from related domains, transfer learning has shown to be effective for cross-domain learning problems. In this dissertation, I carry out research along this direction with a particular focus on designing efficient and effective algorithms for BioImaging and Bilingual applications. Specifically, I propose deep transfer learning algorithms which combine transfer learning and deep learning to improve image annotation performance. Firstly, I propose to generate the deep features for the Drosophila embryo images via pretrained deep models and build linear classifiers on top of the deep features. Secondly, I propose to fine-tune the pretrained model with a small amount of labeled images. The time complexity and performance of deep transfer learning methodologies are investigated. Promising results have demonstrated the knowledge transfer ability of proposed deep transfer algorithms. Moreover, I propose a novel Robust Principal Component Analysis (RPCA) approach to process the noisy images in advance. In addition, I also present a two-stage re-weighting framework for general domain adaptation problems. The distribution of source domain is mapped towards the target domain in the first stage, and an adaptive learning model is proposed in the second stage to incorporate label information from the target domain if it is available. Then the proposed model is applied to tackle cross lingual spam detection problem at LinkedIn’s website. Our experimental results on real data demonstrate the efficiency and effectiveness of the proposed algorithms.
ContributorsSun, Qian (Author) / Ye, Jieping (Committee member) / Xue, Guoliang (Committee member) / Liu, Huan (Committee member) / Li, Jing (Committee member) / Arizona State University (Publisher)
Created2015
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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

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.
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
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Description
Transfer learning refers to statistical machine learning methods that integrate the knowledge of one domain (source domain) and the data of another domain (target domain) in an appropriate way, in order to develop a model for the target domain that is better than a model using the data of the

Transfer learning refers to statistical machine learning methods that integrate the knowledge of one domain (source domain) and the data of another domain (target domain) in an appropriate way, in order to develop a model for the target domain that is better than a model using the data of the target domain alone. Transfer learning emerged because classic machine learning, when used to model different domains, has to take on one of two mechanical approaches. That is, it will either assume the data distributions of the different domains to be the same and thereby developing one model that fits all, or develop one model for each domain independently. Transfer learning, on the other hand, aims to mitigate the limitations of the two approaches by accounting for both the similarity and specificity of related domains. The objective of my dissertation research is to develop new transfer learning methods and demonstrate the utility of the methods in real-world applications. Specifically, in my methodological development, I focus on two different transfer learning scenarios: spatial transfer learning across different domains and temporal transfer learning along time in the same domain. Furthermore, I apply the proposed spatial transfer learning approach to modeling of degenerate biological systems.Degeneracy is a well-known characteristic, widely-existing in many biological systems, and contributes to the heterogeneity, complexity, and robustness of biological systems. In particular, I study the application of one degenerate biological system which is to use transcription factor (TF) binding sites to predict gene expression across multiple cell lines. Also, I apply the proposed temporal transfer learning approach to change detection of dynamic network data. Change detection is a classic research area in Statistical Process Control (SPC), but change detection in network data has been limited studied. I integrate the temporal transfer learning method called the Network State Space Model (NSSM) and SPC and formulate the problem of change detection from dynamic networks into a covariance monitoring problem. I demonstrate the performance of the NSSM in change detection of dynamic social networks.
ContributorsZou, Na (Author) / Li, Jing (Thesis advisor) / Baydogan, Mustafa (Committee member) / Borror, Connie (Committee member) / Montgomery, Douglas C. (Committee member) / Wu, Teresa (Committee member) / Arizona State University (Publisher)
Created2015
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Description
In species with highly heteromorphic sex chromosomes, the degradation of one of the sex chromosomes can result in unequal gene expression between the sexes (e.g., between XX females and XY males) and between the sex chromosomes and the autosomes. Dosage compensation is a process whereby genes on the sex chromosomes

In species with highly heteromorphic sex chromosomes, the degradation of one of the sex chromosomes can result in unequal gene expression between the sexes (e.g., between XX females and XY males) and between the sex chromosomes and the autosomes. Dosage compensation is a process whereby genes on the sex chromosomes achieve equal gene expression which prevents deleterious side effects from having too much or too little expression of genes on sex chromsomes. The green anole is part of a group of species that recently underwent an adaptive radiation. The green anole has XX/XY sex determination, but the content of the X chromosome and its evolution have not been described. Given its status as a model species, better understanding the green anole genome could reveal insights into other species. Genomic analyses are crucial for a comprehensive picture of sex chromosome differentiation and dosage compensation, in addition to understanding speciation.

In order to address this, multiple comparative genomics and bioinformatics analyses were conducted to elucidate patterns of evolution in the green anole and across multiple anole species. Comparative genomics analyses were used to infer additional X-linked loci in the green anole, RNAseq data from male and female samples were anayzed to quantify patterns of sex-biased gene expression across the genome, and the extent of dosage compensation on the anole X chromosome was characterized, providing evidence that the sex chromosomes in the green anole are dosage compensated.

In addition, X-linked genes have a lower ratio of nonsynonymous to synonymous substitution rates than the autosomes when compared to other Anolis species, and pairwise rates of evolution in genes across the anole genome were analyzed. To conduct this analysis a new pipeline was created for filtering alignments and performing batch calculations for whole genome coding sequences. This pipeline has been made publicly available.
ContributorsRupp, Shawn Michael (Author) / Wilson Sayres, Melissa A (Thesis advisor) / Kusumi, Kenro (Committee member) / DeNardo, Dale (Committee member) / Arizona State University (Publisher)
Created2016
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Description
Deep learning is a sub-field of machine learning in which models are developed to imitate the workings of the human brain in processing data and creating patterns for decision making. This dissertation is focused on developing deep learning models for medical imaging analysis of different modalities for different tasks including

Deep learning is a sub-field of machine learning in which models are developed to imitate the workings of the human brain in processing data and creating patterns for decision making. This dissertation is focused on developing deep learning models for medical imaging analysis of different modalities for different tasks including detection, segmentation and classification. Imaging modalities including digital mammography (DM), magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT) are studied in the dissertation for various medical applications. The first phase of the research is to develop a novel shallow-deep convolutional neural network (SD-CNN) model for improved breast cancer diagnosis. This model takes one type of medical image as input and synthesizes different modalities for additional feature sources; both original image and synthetic image are used for feature generation. This proposed architecture is validated in the application of breast cancer diagnosis and proved to be outperforming the competing models. Motivated by the success from the first phase, the second phase focuses on improving medical imaging synthesis performance with advanced deep learning architecture. A new architecture named deep residual inception encoder-decoder network (RIED-Net) is proposed. RIED-Net has the advantages of preserving pixel-level information and cross-modality feature transferring. The applicability of RIED-Net is validated in breast cancer diagnosis and Alzheimer’s disease (AD) staging. Recognizing medical imaging research often has multiples inter-related tasks, namely, detection, segmentation and classification, my third phase of the research is to develop a multi-task deep learning model. Specifically, a feature transfer enabled multi-task deep learning model (FT-MTL-Net) is proposed to transfer high-resolution features from segmentation task to low-resolution feature-based classification task. The application of FT-MTL-Net on breast cancer detection, segmentation and classification using DM images is studied. As a continuing effort on exploring the transfer learning in deep models for medical application, the last phase is to develop a deep learning model for both feature transfer and knowledge from pre-training age prediction task to new domain of Mild cognitive impairment (MCI) to AD conversion prediction task. It is validated in the application of predicting MCI patients’ conversion to AD with 3D MRI images.
ContributorsGao, Fei (Author) / Wu, Teresa (Thesis advisor) / Li, Jing (Committee member) / Yan, Hao (Committee member) / Patel, Bhavika (Committee member) / Arizona State University (Publisher)
Created2019