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In many classication problems data samples cannot be collected easily, example in drug trials, biological experiments and study on cancer patients. In many situations the data set size is small and there are many outliers. When classifying such data, example cancer vs normal patients the consequences of mis-classication are probably

In many classication problems data samples cannot be collected easily, example in drug trials, biological experiments and study on cancer patients. In many situations the data set size is small and there are many outliers. When classifying such data, example cancer vs normal patients the consequences of mis-classication are probably more important than any other data type, because the data point could be a cancer patient or the classication decision could help determine what gene might be over expressed and perhaps a cause of cancer. These mis-classications are typically higher in the presence of outlier data points. The aim of this thesis is to develop a maximum margin classier that is suited to address the lack of robustness of discriminant based classiers (like the Support Vector Machine (SVM)) to noise and outliers. The underlying notion is to adopt and develop a natural loss function that is more robust to outliers and more representative of the true loss function of the data. It is demonstrated experimentally that SVM's are indeed susceptible to outliers and that the new classier developed, here coined as Robust-SVM (RSVM), is superior to all studied classier on the synthetic datasets. It is superior to the SVM in both the synthetic and experimental data from biomedical studies and is competent to a classier derived on similar lines when real life data examples are considered.
ContributorsGupta, Sidharth (Author) / Kim, Seungchan (Thesis advisor) / Welfert, Bruno (Committee member) / Li, Baoxin (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Given the process of tumorigenesis, biological signaling pathways have become of interest in the field of oncology. Many of the regulatory mechanisms that are altered in cancer are directly related to signal transduction and cellular communication. Thus, identifying signaling pathways that have become deregulated may provide useful information

Given the process of tumorigenesis, biological signaling pathways have become of interest in the field of oncology. Many of the regulatory mechanisms that are altered in cancer are directly related to signal transduction and cellular communication. Thus, identifying signaling pathways that have become deregulated may provide useful information to better understanding altered regulatory mechanisms within cancer. Many methods that have been created to measure the distinct activity of signaling pathways have relied strictly upon transcription profiles. With advancements in comparative genomic hybridization techniques, copy number data has become extremely useful in providing valuable information pertaining to the genomic landscape of cancer. The purpose of this thesis is to develop a methodology that incorporates both gene expression and copy number data to identify signaling pathways that have become deregulated in cancer. The central idea is that copy number data may significantly assist in identifying signaling pathway deregulation by justifying the aberrant activity being measured in gene expression profiles. This method was then applied to four different subtypes of breast cancer resulting in the identification of signaling pathways associated with distinct functionalities for each of the breast cancer subtypes.
ContributorsTrevino, Robert (Author) / Kim, Seungchan (Thesis advisor) / Ringner, Markus (Committee member) / Liu, Huan (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Surgery as a profession requires significant training to improve both clinical decision making and psychomotor proficiency. In the medical knowledge domain, tools have been developed, validated, and accepted for evaluation of surgeons' competencies. However, assessment of the psychomotor skills still relies on the Halstedian model of apprenticeship, wherein surgeons are

Surgery as a profession requires significant training to improve both clinical decision making and psychomotor proficiency. In the medical knowledge domain, tools have been developed, validated, and accepted for evaluation of surgeons' competencies. However, assessment of the psychomotor skills still relies on the Halstedian model of apprenticeship, wherein surgeons are observed during residency for judgment of their skills. Although the value of this method of skills assessment cannot be ignored, novel methodologies of objective skills assessment need to be designed, developed, and evaluated that augment the traditional approach. Several sensor-based systems have been developed to measure a user's skill quantitatively, but use of sensors could interfere with skill execution and thus limit the potential for evaluating real-life surgery. However, having a method to judge skills automatically in real-life conditions should be the ultimate goal, since only with such features that a system would be widely adopted. This research proposes a novel video-based approach for observing surgeons' hand and surgical tool movements in minimally invasive surgical training exercises as well as during laparoscopic surgery. Because our system does not require surgeons to wear special sensors, it has the distinct advantage over alternatives of offering skills assessment in both learning and real-life environments. The system automatically detects major skill-measuring features from surgical task videos using a computing system composed of a series of computer vision algorithms and provides on-screen real-time performance feedback for more efficient skill learning. Finally, the machine-learning approach is used to develop an observer-independent composite scoring model through objective and quantitative measurement of surgical skills. To increase effectiveness and usability of the developed system, it is integrated with a cloud-based tool, which automatically assesses surgical videos upload to the cloud.
ContributorsIslam, Gazi (Author) / Li, Baoxin (Thesis advisor) / Liang, Jianming (Thesis advisor) / Dinu, Valentin (Committee member) / Greenes, Robert (Committee member) / Smith, Marshall (Committee member) / Kahol, Kanav (Committee member) / Patel, Vimla L. (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Drosophila melanogaster, as an important model organism, is used to explore the mechanism which governs cell differentiation and embryonic development. Understanding the mechanism will help to reveal the effects of genes on other species or even human beings. Currently, digital camera techniques make high quality Drosophila gene expression imaging possible.

Drosophila melanogaster, as an important model organism, is used to explore the mechanism which governs cell differentiation and embryonic development. Understanding the mechanism will help to reveal the effects of genes on other species or even human beings. Currently, digital camera techniques make high quality Drosophila gene expression imaging possible. On the other hand, due to the advances in biology, gene expression images which can reveal spatiotemporal patterns are generated in a high-throughput pace. Thus, an automated and efficient system that can analyze gene expression will become a necessary tool for investigating the gene functions, interactions and developmental processes. One investigation method is to compare the expression patterns of different developmental stages. Recently, however, the expression patterns are manually annotated with rough stage ranges. The work of annotation requires professional knowledge from experienced biologists. Hence, how to transfer the domain knowledge in biology into an automated system which can automatically annotate the patterns provides a challenging problem for computer scientists. In this thesis, the problem of stage annotation for Drosophila embryo is modeled in the machine learning framework. Three sparse learning algorithms and one ensemble algorithm are used to attack the problem. The sparse algorithms are Lasso, group Lasso and sparse group Lasso. The ensemble algorithm is based on a voting method. Besides that the proposed algorithms can annotate the patterns to stages instead of stage ranges with high accuracy; the decimal stage annotation algorithm presents a novel way to annotate the patterns to decimal stages. In addition, some analysis on the algorithm performance are made and corresponding explanations are given. Finally, with the proposed system, all the lateral view BDGP and FlyFish images are annotated and several interesting applications of decimal stage value are revealed.
ContributorsPan, Cheng (Author) / Ye, Jieping (Thesis advisor) / Li, Baoxin (Committee member) / Farin, Gerald (Committee member) / Arizona State University (Publisher)
Created2012
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Description
We solve the problem of activity verification in the context of sustainability. Activity verification is the process of proving the user assertions pertaining to a certain activity performed by the user. Our motivation lies in incentivizing the user for engaging in sustainable activities like taking public transport or recycling. Such

We solve the problem of activity verification in the context of sustainability. Activity verification is the process of proving the user assertions pertaining to a certain activity performed by the user. Our motivation lies in incentivizing the user for engaging in sustainable activities like taking public transport or recycling. Such incentivization schemes require the system to verify the claim made by the user. The system verifies these claims by analyzing the supporting evidence captured by the user while performing the activity. The proliferation of portable smart-phones in the past few years has provided us with a ubiquitous and relatively cheap platform, having multiple sensors like accelerometer, gyroscope, microphone etc. to capture this evidence data in-situ. In this research, we investigate the supervised and semi-supervised learning techniques for activity verification. Both these techniques make use the data set constructed using the evidence submitted by the user. Supervised learning makes use of annotated evidence data to build a function to predict the class labels of the unlabeled data points. The evidence data captured can be either unimodal or multimodal in nature. We use the accelerometer data as evidence for transportation mode verification and image data as evidence for recycling verification. After training the system, we achieve maximum accuracy of 94% when classifying the transport mode and 81% when detecting recycle activity. In the case of recycle verification, we could improve the classification accuracy by asking the user for more evidence. We present some techniques to ask the user for the next best piece of evidence that maximizes the probability of classification. Using these techniques for detecting recycle activity, the accuracy increases to 93%. The major disadvantage of using supervised models is that it requires extensive annotated training data, which expensive to collect. Due to the limited training data, we look at the graph based inductive semi-supervised learning methods to propagate the labels among the unlabeled samples. In the semi-supervised approach, we represent each instance in the data set as a node in the graph. Since it is a complete graph, edges interconnect these nodes, with each edge having some weight representing the similarity between the points. We propagate the labels in this graph, based on the proximity of the data points to the labeled nodes. We estimate the performance of these algorithms by measuring how close the probability distribution of the data after label propagation is to the probability distribution of the ground truth data. Since labeling has a cost associated with it, in this thesis we propose two algorithms that help us in selecting minimum number of labeled points to propagate the labels accurately. Our proposed algorithm achieves a maximum of 73% increase in performance when compared to the baseline algorithm.
ContributorsDesai, Vaishnav (Author) / Sundaram, Hari (Thesis advisor) / Li, Baoxin (Thesis advisor) / Turaga, Pavan (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Biological systems are complex in many dimensions as endless transportation and communication networks all function simultaneously. Our ability to intervene within both healthy and diseased systems is tied directly to our ability to understand and model core functionality. The progress in increasingly accurate and thorough high-throughput measurement technologies has provided

Biological systems are complex in many dimensions as endless transportation and communication networks all function simultaneously. Our ability to intervene within both healthy and diseased systems is tied directly to our ability to understand and model core functionality. The progress in increasingly accurate and thorough high-throughput measurement technologies has provided a deluge of data from which we may attempt to infer a representation of the true genetic regulatory system. A gene regulatory network model, if accurate enough, may allow us to perform hypothesis testing in the form of computational experiments. Of great importance to modeling accuracy is the acknowledgment of biological contexts within the models -- i.e. recognizing the heterogeneous nature of the true biological system and the data it generates. This marriage of engineering, mathematics and computer science with systems biology creates a cycle of progress between computer simulation and lab experimentation, rapidly translating interventions and treatments for patients from the bench to the bedside. This dissertation will first discuss the landscape for modeling the biological system, explore the identification of targets for intervention in Boolean network models of biological interactions, and explore context specificity both in new graphical depictions of models embodying context-specific genomic regulation and in novel analysis approaches designed to reveal embedded contextual information. Overall, the dissertation will explore a spectrum of biological modeling with a goal towards therapeutic intervention, with both formal and informal notions of biological context, in such a way that will enable future work to have an even greater impact in terms of direct patient benefit on an individualized level.
ContributorsVerdicchio, Michael (Author) / Kim, Seungchan (Thesis advisor) / Baral, Chitta (Committee member) / Stolovitzky, Gustavo (Committee member) / Collofello, James (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Threshold logic has been studied by at least two independent group of researchers. One group of researchers studied threshold logic with the intention of building threshold logic circuits. The earliest research to this end was done in the 1960's. The major work at that time focused on studying mathematical properties

Threshold logic has been studied by at least two independent group of researchers. One group of researchers studied threshold logic with the intention of building threshold logic circuits. The earliest research to this end was done in the 1960's. The major work at that time focused on studying mathematical properties of threshold logic as no efficient circuit implementations of threshold logic were available. Recently many post-CMOS (Complimentary Metal Oxide Semiconductor) technologies that implement threshold logic have been proposed along with efficient CMOS implementations. This has renewed the effort to develop efficient threshold logic design automation techniques. This work contributes to this ongoing effort. Another group studying threshold logic did so, because the building block of neural networks - the Perceptron, is identical to the threshold element implementing a threshold function. Neural networks are used for various purposes as data classifiers. This work contributes tangentially to this field by proposing new methods and techniques to study and analyze functions implemented by a Perceptron After completion of the Human Genome Project, it has become evident that most biological phenomenon is not caused by the action of single genes, but due to the complex interaction involving a system of genes. In recent times, the `systems approach' for the study of gene systems is gaining popularity. Many different theories from mathematics and computer science has been used for this purpose. Among the systems approaches, the Boolean logic gene model has emerged as the current most popular discrete gene model. This work proposes a new gene model based on threshold logic functions (which are a subset of Boolean logic functions). The biological relevance and utility of this model is argued illustrated by using it to model different in-vivo as well as in-silico gene systems.
ContributorsLinge Gowda, Tejaswi (Author) / Vrudhula, Sarma (Thesis advisor) / Shrivastava, Aviral (Committee member) / Chatha, Karamvir (Committee member) / Kim, Seungchan (Committee member) / Arizona State University (Publisher)
Created2012
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Description
As we migrate into an era of personalized medicine, understanding how bio-molecules interact with one another to form cellular systems is one of the key focus areas of systems biology. Several challenges such as the dynamic nature of cellular systems, uncertainty due to environmental influences, and the heterogeneity between individual

As we migrate into an era of personalized medicine, understanding how bio-molecules interact with one another to form cellular systems is one of the key focus areas of systems biology. Several challenges such as the dynamic nature of cellular systems, uncertainty due to environmental influences, and the heterogeneity between individual patients render this a difficult task. In the last decade, several algorithms have been proposed to elucidate cellular systems from data, resulting in numerous data-driven hypotheses. However, due to the large number of variables involved in the process, many of which are unknown or not measurable, such computational approaches often lead to a high proportion of false positives. This renders interpretation of the data-driven hypotheses extremely difficult. Consequently, a dismal proportion of these hypotheses are subject to further experimental validation, eventually limiting their potential to augment existing biological knowledge. This dissertation develops a framework of computational methods for the analysis of such data-driven hypotheses leveraging existing biological knowledge. Specifically, I show how biological knowledge can be mapped onto these hypotheses and subsequently augmented through novel hypotheses. Biological hypotheses are learnt in three levels of abstraction -- individual interactions, functional modules and relationships between pathways, corresponding to three complementary aspects of biological systems. The computational methods developed in this dissertation are applied to high throughput cancer data, resulting in novel hypotheses with potentially significant biological impact.
ContributorsRamesh, Archana (Author) / Kim, Seungchan (Thesis advisor) / Langley, Patrick W (Committee member) / Baral, Chitta (Committee member) / Kiefer, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Continuous advancements in biomedical research have resulted in the production of vast amounts of scientific data and literature discussing them. The ultimate goal of computational biology is to translate these large amounts of data into actual knowledge of the complex biological processes and accurate life science models. The ability to

Continuous advancements in biomedical research have resulted in the production of vast amounts of scientific data and literature discussing them. The ultimate goal of computational biology is to translate these large amounts of data into actual knowledge of the complex biological processes and accurate life science models. The ability to rapidly and effectively survey the literature is necessary for the creation of large scale models of the relationships among biomedical entities as well as hypothesis generation to guide biomedical research. To reduce the effort and time spent in performing these activities, an intelligent search system is required. Even though many systems aid in navigating through this wide collection of documents, the vastness and depth of this information overload can be overwhelming. An automated extraction system coupled with a cognitive search and navigation service over these document collections would not only save time and effort, but also facilitate discovery of the unknown information implicitly conveyed in the texts. This thesis presents the different approaches used for large scale biomedical named entity recognition, and the challenges faced in each. It also proposes BioEve: an integrative framework to fuse a faceted search with information extraction to provide a search service that addresses the user's desire for "completeness" of the query results, not just the top-ranked ones. This information extraction system enables discovery of important semantic relationships between entities such as genes, diseases, drugs, and cell lines and events from biomedical text on MEDLINE, which is the largest publicly available database of the world's biomedical journal literature. It is an innovative search and discovery service that makes it easier to search
avigate and discover knowledge hidden in life sciences literature. To demonstrate the utility of this system, this thesis also details a prototype enterprise quality search and discovery service that helps researchers with a guided step-by-step query refinement, by suggesting concepts enriched in intermediate results, and thereby facilitating the "discover more as you search" paradigm.
ContributorsKanwar, Pradeep (Author) / Davulcu, Hasan (Thesis advisor) / Dinu, Valentin (Committee member) / Li, Baoxin (Committee member) / Arizona State University (Publisher)
Created2010
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Description
Cardiovascular disease (CVD) is the leading cause of mortality yet largely preventable, but the key to prevention is to identify at-risk individuals before adverse events. For predicting individual CVD risk, carotid intima-media thickness (CIMT), a noninvasive ultrasound method, has proven to be valuable, offering several advantages over CT coronary artery

Cardiovascular disease (CVD) is the leading cause of mortality yet largely preventable, but the key to prevention is to identify at-risk individuals before adverse events. For predicting individual CVD risk, carotid intima-media thickness (CIMT), a noninvasive ultrasound method, has proven to be valuable, offering several advantages over CT coronary artery calcium score. However, each CIMT examination includes several ultrasound videos, and interpreting each of these CIMT videos involves three operations: (1) select three enddiastolic ultrasound frames (EUF) in the video, (2) localize a region of interest (ROI) in each selected frame, and (3) trace the lumen-intima interface and the media-adventitia interface in each ROI to measure CIMT. These operations are tedious, laborious, and time consuming, a serious limitation that hinders the widespread utilization of CIMT in clinical practice. To overcome this limitation, this paper presents a new system to automate CIMT video interpretation. Our extensive experiments demonstrate that the suggested system significantly outperforms the state-of-the-art methods. The superior performance is attributable to our unified framework based on convolutional neural networks (CNNs) coupled with our informative image representation and effective post-processing of the CNN outputs, which are uniquely designed for each of the above three operations.
ContributorsShin, Jaeyul (Author) / Liang, Jianming (Thesis advisor) / Maciejewski, Ross (Committee member) / Li, Baoxin (Committee member) / Arizona State University (Publisher)
Created2016