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- All Subjects: Bioinformatics
- Genre: Academic theses
- Creators: Ye, Jieping
- Creators: Gonzalez, Graciela
- Member of: ASU Electronic Theses and Dissertations
- Resource Type: Text
Description
Sparsity has become an important modeling tool in areas such as genetics, signal and audio processing, medical image processing, etc. Via the penalization of l-1 norm based regularization, the structured sparse learning algorithms can produce highly accurate models while imposing various predefined structures on the data, such as feature groups or graphs. In this thesis, I first propose to solve a sparse learning model with a general group structure, where the predefined groups may overlap with each other. Then, I present three real world applications which can benefit from the group structured sparse learning technique. In the first application, I study the Alzheimer's Disease diagnosis problem using multi-modality neuroimaging data. In this dataset, not every subject has all data sources available, exhibiting an unique and challenging block-wise missing pattern. In the second application, I study the automatic annotation and retrieval of fruit-fly gene expression pattern images. Combined with the spatial information, sparse learning techniques can be used to construct effective representation of the expression images. In the third application, I present a new computational approach to annotate developmental stage for Drosophila embryos in the gene expression images. In addition, it provides a stage score that enables one to more finely annotate each embryo so that they are divided into early and late periods of development within standard stage demarcations. Stage scores help us to illuminate global gene activities and changes much better, and more refined stage annotations improve our ability to better interpret results when expression pattern matches are discovered between genes.
ContributorsYuan, Lei (Author) / Ye, Jieping (Thesis advisor) / Wang, Yalin (Committee member) / Xue, Guoliang (Committee member) / Kumar, Sudhir (Committee member) / Arizona State University (Publisher)
Created2013
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
In many fields one needs to build predictive models for a set of related machine learning tasks, such as information retrieval, computer vision and biomedical informatics. Traditionally these tasks are treated independently and the inference is done separately for each task, which ignores important connections among the tasks. Multi-task learning aims at simultaneously building models for all tasks in order to improve the generalization performance, leveraging inherent relatedness of these tasks. In this thesis, I firstly propose a clustered multi-task learning (CMTL) formulation, which simultaneously learns task models and performs task clustering. I provide theoretical analysis to establish the equivalence between the CMTL formulation and the alternating structure optimization, which learns a shared low-dimensional hypothesis space for different tasks. Then I present two real-world biomedical informatics applications which can benefit from multi-task learning. In the first application, I study the disease progression problem and present multi-task learning formulations for disease progression. In the formulations, the prediction at each point is a regression task and multiple tasks at different time points are learned simultaneously, leveraging the temporal smoothness among the tasks. The proposed formulations have been tested extensively on predicting the progression of the Alzheimer's disease, and experimental results demonstrate the effectiveness of the proposed models. In the second application, I present a novel data-driven framework for densifying the electronic medical records (EMR) to overcome the sparsity problem in predictive modeling using EMR. The densification of each patient is a learning task, and the proposed algorithm simultaneously densify all patients. As such, the densification of one patient leverages useful information from other patients.
ContributorsZhou, Jiayu (Author) / Ye, Jieping (Thesis advisor) / Mittelmann, Hans (Committee member) / Li, Baoxin (Committee member) / Wang, Yalin (Committee member) / Arizona State University (Publisher)
Created2014
Description
Genes have widely different pertinences to the etiology and pathology of diseases. Thus, they can be ranked according to their disease-significance on a genomic scale, which is the subject of gene prioritization. Given a set of genes known to be related to a disease, it is reasonable to use them as a basis to determine the significance of other candidate genes, which will then be ranked based on the association they exhibit with respect to the given set of known genes. Experimental and computational data of various kinds have different reliability and relevance to a disease under study. This work presents a gene prioritization method based on integrated biological networks that incorporates and models the various levels of relevance and reliability of diverse sources. The method is shown to achieve significantly higher performance as compared to two well-known gene prioritization algorithms. Essentially, no bias in the performance was seen as it was applied to diseases of diverse ethnology, e.g., monogenic, polygenic and cancer. The method was highly stable and robust against significant levels of noise in the data. Biological networks are often sparse, which can impede the operation of associationbased gene prioritization algorithms such as the one presented here from a computational perspective. As a potential approach to overcome this limitation, we explore the value that transcription factor binding sites can have in elucidating suitable targets. Transcription factors are needed for the expression of most genes, especially in higher organisms and hence genes can be associated via their genetic regulatory properties. While each transcription factor recognizes specific DNA sequence patterns, such patterns are mostly unknown for many transcription factors. Even those that are known are inconsistently reported in the literature, implying a potentially high level of inaccuracy. We developed computational methods for prediction and improvement of transcription factor binding patterns. Tests performed on the improvement method by employing synthetic patterns under various conditions showed that the method is very robust and the patterns produced invariably converge to nearly identical series of patterns. Preliminary tests were conducted to incorporate knowledge from transcription factor binding sites into our networkbased model for prioritization, with encouraging results. Genes have widely different pertinences to the etiology and pathology of diseases. Thus, they can be ranked according to their disease-significance on a genomic scale, which is the subject of gene prioritization. Given a set of genes known to be related to a disease, it is reasonable to use them as a basis to determine the significance of other candidate genes, which will then be ranked based on the association they exhibit with respect to the given set of known genes. Experimental and computational data of various kinds have different reliability and relevance to a disease under study. This work presents a gene prioritization method based on integrated biological networks that incorporates and models the various levels of relevance and reliability of diverse sources. The method is shown to achieve significantly higher performance as compared to two well-known gene prioritization algorithms. Essentially, no bias in the performance was seen as it was applied to diseases of diverse ethnology, e.g., monogenic, polygenic and cancer. The method was highly stable and robust against significant levels of noise in the data. Biological networks are often sparse, which can impede the operation of associationbased gene prioritization algorithms such as the one presented here from a computational perspective. As a potential approach to overcome this limitation, we explore the value that transcription factor binding sites can have in elucidating suitable targets. Transcription factors are needed for the expression of most genes, especially in higher organisms and hence genes can be associated via their genetic regulatory properties. While each transcription factor recognizes specific DNA sequence patterns, such patterns are mostly unknown for many transcription factors. Even those that are known are inconsistently reported in the literature, implying a potentially high level of inaccuracy. We developed computational methods for prediction and improvement of transcription factor binding patterns. Tests performed on the improvement method by employing synthetic patterns under various conditions showed that the method is very robust and the patterns produced invariably converge to nearly identical series of patterns. Preliminary tests were conducted to incorporate knowledge from transcription factor binding sites into our networkbased model for prioritization, with encouraging results. To validate these approaches in a disease-specific context, we built a schizophreniaspecific network based on the inferred associations and performed a comprehensive prioritization of human genes with respect to the disease. These results are expected to be validated empirically, but computational validation using known targets are very positive.
ContributorsLee, Jang (Author) / Gonzalez, Graciela (Thesis advisor) / Ye, Jieping (Committee member) / Davulcu, Hasan (Committee member) / Gallitano-Mendel, Amelia (Committee member) / Arizona State University (Publisher)
Created2011
Description
Detecting anatomical structures, such as the carina, the pulmonary trunk and the aortic arch, is an important step in designing a CAD system of detection Pulmonary Embolism. The presented CAD system gets rid of the high-level prior defined knowledge to become a system which can easily extend to detect other anatomic structures. The system is based on a machine learning algorithm --- AdaBoost and a general feature --- Haar. This study emphasizes on off-line and on-line AdaBoost learning. And in on-line AdaBoost, the thesis further deals with extremely imbalanced condition. The thesis first reviews several knowledge-based detection methods, which are relied on human being's understanding of the relationship between anatomic structures. Then the thesis introduces a classic off-line AdaBoost learning. The thesis applies different cascading scheme, namely multi-exit cascading scheme. The comparison between the two methods will be provided and discussed. Both of the off-line AdaBoost methods have problems in memory usage and time consuming. Off-line AdaBoost methods need to store all the training samples and the dataset need to be set before training. The dataset cannot be enlarged dynamically. Different training dataset requires retraining the whole process. The retraining is very time consuming and even not realistic. To deal with the shortcomings of off-line learning, the study exploited on-line AdaBoost learning approach. The thesis proposed a novel pool based on-line method with Kalman filters and histogram to better represent the distribution of the samples' weight. Analysis of the performance, the stability and the computational complexity will be provided in the thesis. Furthermore, the original on-line AdaBoost performs badly in imbalanced conditions, which occur frequently in medical image processing. In image dataset, positive samples are limited and negative samples are countless. A novel Self-Adaptive Asymmetric On-line Boosting method is presented. The method utilized a new asymmetric loss criterion with self-adaptability according to the ratio of exposed positive and negative samples and it has an advanced rule to update sample's importance weight taking account of both classification result and sample's label. Compared to traditional on-line AdaBoost Learning method, the new method can achieve far more accuracy in imbalanced conditions.
ContributorsWu, Hong (Author) / Liang, Jianming (Thesis advisor) / Farin, Gerald (Committee member) / Ye, Jieping (Committee member) / Arizona State University (Publisher)
Created2011
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
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
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.
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
Description
Social media is becoming increasingly popular as a platform for sharing personal health-related information. This information can be utilized for public health monitoring tasks such as pharmacovigilance via the use of Natural Language Processing (NLP) techniques. One of the critical steps in information extraction pipelines is Named Entity Recognition (NER), where the mentions of entities such as diseases are located in text and their entity type are identified. However, the language in social media is highly informal, and user-expressed health-related concepts are often non-technical, descriptive, and challenging to extract. There has been limited progress in addressing these challenges, and advanced machine learning-based NLP techniques have been underutilized. This work explores the effectiveness of different machine learning techniques, and particularly deep learning, to address the challenges associated with extraction of health-related concepts from social media. Deep learning has recently attracted a lot of attention in machine learning research and has shown remarkable success in several applications particularly imaging and speech recognition. However, thus far, deep learning techniques are relatively unexplored for biomedical text mining and, in particular, this is the first attempt in applying deep learning for health information extraction from social media.
This work presents ADRMine that uses a Conditional Random Field (CRF) sequence tagger for extraction of complex health-related concepts. It utilizes a large volume of unlabeled user posts for automatic learning of embedding cluster features, a novel application of deep learning in modeling the similarity between the tokens. ADRMine significantly improved the medical NER performance compared to the baseline systems.
This work also presents DeepHealthMiner, a deep learning pipeline for health-related concept extraction. Most of the machine learning methods require sophisticated task-specific manual feature design which is a challenging step in processing the informal and noisy content of social media. DeepHealthMiner automatically learns classification features using neural networks and utilizing a large volume of unlabeled user posts. Using a relatively small labeled training set, DeepHealthMiner could accurately identify most of the concepts, including the consumer expressions that were not observed in the training data or in the standard medical lexicons outperforming the state-of-the-art baseline techniques.
This work presents ADRMine that uses a Conditional Random Field (CRF) sequence tagger for extraction of complex health-related concepts. It utilizes a large volume of unlabeled user posts for automatic learning of embedding cluster features, a novel application of deep learning in modeling the similarity between the tokens. ADRMine significantly improved the medical NER performance compared to the baseline systems.
This work also presents DeepHealthMiner, a deep learning pipeline for health-related concept extraction. Most of the machine learning methods require sophisticated task-specific manual feature design which is a challenging step in processing the informal and noisy content of social media. DeepHealthMiner automatically learns classification features using neural networks and utilizing a large volume of unlabeled user posts. Using a relatively small labeled training set, DeepHealthMiner could accurately identify most of the concepts, including the consumer expressions that were not observed in the training data or in the standard medical lexicons outperforming the state-of-the-art baseline techniques.
ContributorsNikfarjam, Azadeh (Author) / Gonzalez, Graciela (Thesis advisor) / Greenes, Robert (Committee member) / Scotch, Matthew (Committee member) / Arizona State University (Publisher)
Created2016
Description
Major Depression, clinically called Major Depressive Disorder, is a mood disorder that affects about one eighth of population in US and is projected to be the second leading cause of disability in the world by the year 2020. Recent advances in biotechnology have enabled us to collect a great variety of data which could potentially offer us a deeper understanding of the disorder as well as advancing personalized medicine.
This dissertation focuses on developing methods for three different aspects of predictive analytics related to the disorder: automatic diagnosis, prognosis, and prediction of long-term treatment outcome. The data used for each task have their specific characteristics and demonstrate unique problems. Automatic diagnosis of melancholic depression is made on the basis of metabolic profiles and micro-array gene expression profiles where the presence of missing values and strong empirical correlation between the variables is not unusual. To deal with these problems, a method of generating a representative set of features is proposed. Prognosis is made on data collected from rating scales and questionnaires which consist mainly of categorical and ordinal variables and thus favor decision tree based predictive models. Decision tree models are known for the notorious problem of overfitting. A decision tree pruning method that overcomes the shortcomings of a greedy nature and reliance on heuristics inherent in traditional decision tree pruning approaches is proposed. The method is further extended to prune Gradient Boosting Decision Tree and tested on the task of prognosis of treatment outcome. Follow-up studies evaluating the long-term effect of the treatments on patients usually measure patients' depressive symptom severity monthly, resulting in the actual time of relapse upper bounded by the observed time of relapse. To resolve such uncertainty in response, a general loss function where the hypothesis could take different forms is proposed to predict the risk of relapse in situations where only an interval for time of relapse can be derived from the observed data.
This dissertation focuses on developing methods for three different aspects of predictive analytics related to the disorder: automatic diagnosis, prognosis, and prediction of long-term treatment outcome. The data used for each task have their specific characteristics and demonstrate unique problems. Automatic diagnosis of melancholic depression is made on the basis of metabolic profiles and micro-array gene expression profiles where the presence of missing values and strong empirical correlation between the variables is not unusual. To deal with these problems, a method of generating a representative set of features is proposed. Prognosis is made on data collected from rating scales and questionnaires which consist mainly of categorical and ordinal variables and thus favor decision tree based predictive models. Decision tree models are known for the notorious problem of overfitting. A decision tree pruning method that overcomes the shortcomings of a greedy nature and reliance on heuristics inherent in traditional decision tree pruning approaches is proposed. The method is further extended to prune Gradient Boosting Decision Tree and tested on the task of prognosis of treatment outcome. Follow-up studies evaluating the long-term effect of the treatments on patients usually measure patients' depressive symptom severity monthly, resulting in the actual time of relapse upper bounded by the observed time of relapse. To resolve such uncertainty in response, a general loss function where the hypothesis could take different forms is proposed to predict the risk of relapse in situations where only an interval for time of relapse can be derived from the observed data.
ContributorsNie, Zhi (Author) / Ye, Jieping (Thesis advisor) / He, Jingrui (Thesis advisor) / Li, Baoxin (Committee member) / Xue, Guoliang (Committee member) / Li, Jing (Committee member) / Arizona State University (Publisher)
Created2017