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- Genre: Doctoral Dissertation
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 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
Description
This dissertation investigates the condition of skeletal muscle insulin resistance using bioinformatics and computational biology approaches. Drawing from several studies and numerous data sources, I have attempted to uncover molecular mechanisms at multiple levels. From the detailed atomistic simulations of a single protein, to datamining approaches applied at the systems biology level, I provide new targets to explore for the research community. Furthermore I present a new online web resource that unifies various bioinformatics databases to enable discovery of relevant features in 3D protein structures.
ContributorsMielke, Clinton (Author) / Mandarino, Lawrence (Committee member) / LaBaer, Joshua (Committee member) / Magee, D. Mitchell (Committee member) / Dinu, Valentin (Committee member) / Willis, Wayne (Committee member) / Arizona State University (Publisher)
Created2013
Description
The living world we inhabit and observe is extraordinarily complex. From the perspective of a person analyzing data about the living world, complexity is most commonly encountered in two forms: 1) in the sheer size of the datasets that must be analyzed and the physical number of mathematical computations necessary to obtain an answer and 2) in the underlying structure of the data, which does not conform to classical normal theory statistical assumptions and includes clustering and unobserved latent constructs. Until recently, the methods and tools necessary to effectively address the complexity of biomedical data were not ordinarily available. The utility of four methods--High Performance Computing, Monte Carlo Simulations, Multi-Level Modeling and Structural Equation Modeling--designed to help make sense of complex biomedical data are presented here.
ContributorsBrown, Justin Reed (Author) / Dinu, Valentin (Thesis advisor) / Johnson, William (Committee member) / Petitti, Diana (Committee member) / Arizona State University (Publisher)
Created2012
Description
Critical care environments are complex in nature. Fluctuating team dynamics and the plethora of technology and equipment create unforeseen demands on clinicians. Such environments become chaotic very quickly due to the chronic exposure to unpredictable clusters of events. In order to cope with this complexity, clinicians tend to develop ad-hoc adaptations to function in an effective manner. It is these adaptations or "deviations" from expected behaviors that provide insight into the processes that shape the overall behavior of the complex system. The research described in this manuscript examines the cognitive basis of clinicians' adaptive mechanisms and presents a methodology for studying the same. Examining interactions in complex systems is difficult due to the disassociation between the nature of the environment and the tools available to analyze underlying processes. In this work, the use of a mixed methodology framework to study trauma critical care, a complex environment, is presented. The hybrid framework supplements existing methods of data collection (qualitative observations) with quantitative methods (use of electronic tags) to capture activities in the complex system. Quantitative models of activities (using Hidden Markov Modeling) and theoretical models of deviations were developed to support this mixed methodology framework. The quantitative activity models developed were tested with a set of fifteen simulated activities that represent workflow in trauma care. A mean recognition rate of 87.5% was obtained in automatically recognizing activities. Theoretical models, on the other hand, were developed using field observations of 30 trauma cases. The analysis of the classification schema (with substantial inter-rater reliability) and 161 deviations identified shows that expertise and role played by the clinician in the trauma team influences the nature of deviations made (p<0.01). The results shows that while expert clinicians deviate to innovate, deviations of novices often result in errors. Experts' flexibility and adaptiveness allow their deviations to generate innovative ideas, in particular when dynamic adjustments are required in complex situations. The findings suggest that while adherence to protocols and standards is important for novice practitioners to reduce medical errors and ensure patient safety, there is strong need for training novices in coping with complex situations as well.
ContributorsVankipuram, Mithra (Author) / Greenes, Robert A (Thesis advisor) / Patel, Vimla L. (Thesis advisor) / Petitti, Diana B. (Committee member) / Dinu, Valentin (Committee member) / Smith, Marshall L. (Committee member) / Arizona State University (Publisher)
Created2012
Description
This work involved the analysis of a public health system, and the design, development and deployment of enterprise informatics architecture, and sustainable community methods to address problems with the current public health system. Specifically, assessment of the Nationally Notifiable Disease Surveillance System (NNDSS) was instrumental in forming the design of the current implementation at the Southern Nevada Health District (SNHD). The result of the system deployment at SNHD was considered as a basis for projecting the practical application and benefits of an enterprise architecture. This approach has resulted in a sustainable platform to enhance the practice of public health by improving the quality and timeliness of data, effectiveness of an investigation, and reporting across the continuum.
ContributorsKriseman, Jeffrey Michael (Author) / Dinu, Valentin (Thesis advisor) / Greenes, Robert (Committee member) / Johnson, William (Committee member) / Arizona State University (Publisher)
Created2012
Description
Immunosignaturing is a technology that allows the humoral immune response to be observed through the binding of antibodies to random sequence peptides. The immunosignaturing microarray is based on complex mixtures of antibodies binding to arrays of random sequence peptides in a multiplexed fashion. There are computational and statistical challenges to the analysis of immunosignaturing data. The overall aim of my dissertation is to develop novel computational and statistical methods for immunosignaturing data to access its potential for diagnostics and drug discovery. Firstly, I discovered that a classification algorithm Naive Bayes which leverages the biological independence of the probes on our array in such a way as to gather more information outperforms other classification algorithms due to speed and accuracy. Secondly, using this classifier, I then tested the specificity and sensitivity of immunosignaturing platform for its ability to resolve four different diseases (pancreatic cancer, pancreatitis, type 2 diabetes and panIN) that target the same organ (pancreas). These diseases were separated with >90% specificity from controls and from each other. Thirdly, I observed that the immunosignature of type 2 diabetes and cardiovascular complications are unique, consistent, and reproducible and can be separated by 100% accuracy from controls. But when these two complications arise in the same person, the resultant immunosignature is quite different in that of individuals with only one disease. I developed a method to trace back from informative random peptides in disease signatures to the potential antigen(s). Hence, I built a decipher system to trace random peptides in type 1 diabetes immunosignature to known antigens. Immunosignaturing, unlike the ELISA, has the ability to not only detect the presence of response but also absence of response during a disease. I observed, not only higher but also lower peptides intensities can be mapped to antigens in type 1 diabetes. To study immunosignaturing potential for population diagnostics, I studied effect of age, gender and geographical location on immunosignaturing data. For its potential to be a health monitoring technology, I proposed a single metric Coefficient of Variation that has shown potential to change significantly when a person enters a disease state.
ContributorsKukreja, Muskan (Author) / Johnston, Stephen Albert (Thesis advisor) / Stafford, Phillip (Committee member) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2012
Description
High throughput transcriptome data analysis like Single-cell Ribonucleic Acid sequencing (scRNA-seq) and Circular Ribonucleic Acid (circRNA) data have made significant breakthroughs, especially in cancer genomics. Analysis of transcriptome time series data is core in identifying time point(s) where drastic changes in gene transcription are associated with homeostatic to non-homeostatic cellular transition (tipping points). In Chapter 2 of this dissertation, I present a novel cell-type specific and co-expression-based tipping point detection method to identify target gene (TG) versus transcription factor (TF) pairs whose differential co-expression across time points drive biological changes in different cell types and the time point when these changes are observed. This method was applied to scRNA-seq data sets from a SARS-CoV-2 study (18 time points), a human cerebellum development study (9 time points), and a lung injury study (18 time points). Similarly, leveraging transcriptome data across treatment time points, I developed methodologies to identify treatment-induced and cell-type specific differentially co-expressed pairs (DCEPs). In part one of Chapter 3, I presented a pipeline that used a series of statistical tests to detect DCEPs. This method was applied to scRNA-seq data of patients with non-small cell lung cancer (NSCLC) sequenced across cancer treatment times. However, this pipeline does not account for correlations among multiple single cells from the same sample and correlations among multiple samples from the same patient. In Part 2 of Chapter 3, I presented a solution to this problem using a mixed-effect model. In Chapter 4, I present a summary of my work that focused on the cross-species analysis of circRNA transcriptome time series data. I compared circRNA profiles in neonatal pig and mouse hearts, identified orthologous circRNAs, and discussed regulation mechanisms of cardiomyocyte proliferation and myocardial regeneration conserved between mouse and pig at different time points.
ContributorsNyarige, Verah Mocheche (Author) / Liu, Li (Thesis advisor) / Wang, Junwen (Thesis advisor) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2022
Description
Advancements in high-throughput biotechnologies have generated large-scale multi-omics datasets encompassing diverse dimensions such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, and phenomics. Traditionally, statistical and machine learning-based approaches utilize single-omics data sources to uncover molecular signatures, dissect complicated cellular mechanisms, and predict clinical results. However, to capture the multifaceted pathological mechanisms, integrative multi-omics analysis is needed that can provide a comprehensive picture of the disease. Here, I present three novel approaches to multi-omics integrative analysis. I introduce a single-cell integrative clustering method, which leverages multi-omics to enhance the resolution of cell subpopulations. Applied to a Cellular Indexing of Transcriptomes and Epitopes (CITE-Seq) dataset from human Acute Myeloid Lymphoma (AML) and control samples, this approach unveiled nuanced cell populations that otherwise remain elusive. I then shift the focus to a computational framework to discover transcriptional regulatory trios in which a transcription factor binds to a regulatory element harboring a genetic variant and subsequently differentially regulates the transcription level of a target gene. Applied to whole-exome, whole-genome, and transcriptome data of multiple myeloma samples, this approach discovered synergetic cis-acting and trans-acting regulatory elements associated with tumorigenesis. The next part of this work introduces a novel methodology that leverages the transcriptome and surface protein data at the single-cell level produced by CITE-Seq to model the intracellular protein trafficking process. Applied to COVID-19 samples, this approach revealed dysregulated protein trafficking associated with the severity of the infection.
ContributorsMudappathi, Rekha (Author) / Liu, Li (Thesis advisor) / Dinu, Valentin (Committee member) / Sun, Zhifu (Committee member) / Arizona State University (Publisher)
Created2023
Description
Circular RNAs (circRNAs) are a class of endogenous, non-coding RNAs that are formed when exons back-splice to each other and represent a new area of transcriptomics research. Numerous RNA sequencing (RNAseq) studies since 2012 have revealed that circRNAs are pervasively expressed in eukaryotes, especially in the mammalian brain. While their functional role and impact remains to be clarified, circRNAs have been found to regulate micro-RNAs (miRNAs) as well as parental gene transcription and may thus have key roles in transcriptional regulation. Although circRNAs have continued to gain attention, our understanding of their expression in a cell-, tissue- , and brain region-specific context remains limited. Further, computational algorithms produce varied results in terms of what circRNAs are detected. This thesis aims to advance current knowledge of circRNA expression in a region specific context focusing on the human brain, as well as address computational challenges.
The overarching goal of my research unfolds over three aims: (i) evaluating circRNAs and their predicted impact on transcriptional regulatory networks in cell-specific RNAseq data; (ii) developing a novel solution for de novo detection of full length circRNAs as well as in silico validation of selected circRNA junctions using assembly; and (iii) application of these assembly based detection and validation workflows, and integrating existing tools, to systematically identify and characterize circRNAs in functionally distinct human brain regions. To this end, I have developed novel bioinformatics workflows that are applicable to non-polyA selected RNAseq datasets and can be used to characterize circRNA expression across various sample types and diseases. Further, I establish a reference dataset of circRNA expression profiles and regulatory networks in a brain region-specific manner. This resource along with existing databases such as circBase will be invaluable in advancing circRNA research as well as improving our understanding of their role in transcriptional regulation and various neurological conditions.
The overarching goal of my research unfolds over three aims: (i) evaluating circRNAs and their predicted impact on transcriptional regulatory networks in cell-specific RNAseq data; (ii) developing a novel solution for de novo detection of full length circRNAs as well as in silico validation of selected circRNA junctions using assembly; and (iii) application of these assembly based detection and validation workflows, and integrating existing tools, to systematically identify and characterize circRNAs in functionally distinct human brain regions. To this end, I have developed novel bioinformatics workflows that are applicable to non-polyA selected RNAseq datasets and can be used to characterize circRNA expression across various sample types and diseases. Further, I establish a reference dataset of circRNA expression profiles and regulatory networks in a brain region-specific manner. This resource along with existing databases such as circBase will be invaluable in advancing circRNA research as well as improving our understanding of their role in transcriptional regulation and various neurological conditions.
ContributorsSekar, Shobana (Author) / Liang, Winnie S (Thesis advisor) / Dinu, Valentin (Thesis advisor) / Craig, David (Committee member) / Liu, Li (Committee member) / Arizona State University (Publisher)
Created2018
Description
Clinical Decision Support (CDS) is primarily associated with alerts, reminders, order entry, rule-based invocation, diagnostic aids, and on-demand information retrieval. While valuable, these foci have been in production use for decades, and do not provide a broader, interoperable means of plugging structured clinical knowledge into live electronic health record (EHR) ecosystems for purposes of orchestrating the user experiences of patients and clinicians. To date, the gap between knowledge representation and user-facing EHR integration has been considered an “implementation concern” requiring unscalable manual human efforts and governance coordination. Drafting a questionnaire engineered to meet the specifications of the HL7 CDS Knowledge Artifact specification, for example, carries no reasonable expectation that it may be imported and deployed into a live system without significant burdens. Dramatic reduction of the time and effort gap in the research and application cycle could be revolutionary. Doing so, however, requires both a floor-to-ceiling precoordination of functional boundaries in the knowledge management lifecycle, as well as formalization of the human processes by which this occurs.
This research introduces ARTAKA: Architecture for Real-Time Application of Knowledge Artifacts, as a concrete floor-to-ceiling technological blueprint for both provider heath IT (HIT) and vendor organizations to incrementally introduce value into existing systems dynamically. This is made possible by service-ization of curated knowledge artifacts, then injected into a highly scalable backend infrastructure by automated orchestration through public marketplaces. Supplementary examples of client app integration are also provided. Compilation of knowledge into platform-specific form has been left flexible, in so far as implementations comply with ARTAKA’s Context Event Service (CES) communication and Health Services Platform (HSP) Marketplace service packaging standards.
Towards the goal of interoperable human processes, ARTAKA’s treatment of knowledge artifacts as a specialized form of software allows knowledge engineers to operate as a type of software engineering practice. Thus, nearly a century of software development processes, tools, policies, and lessons offer immediate benefit: in some cases, with remarkable parity. Analyses of experimentation is provided with guidelines in how choice aspects of software development life cycles (SDLCs) apply to knowledge artifact development in an ARTAKA environment.
Portions of this culminating document have been further initiated with Standards Developing Organizations (SDOs) intended to ultimately produce normative standards, as have active relationships with other bodies.
This research introduces ARTAKA: Architecture for Real-Time Application of Knowledge Artifacts, as a concrete floor-to-ceiling technological blueprint for both provider heath IT (HIT) and vendor organizations to incrementally introduce value into existing systems dynamically. This is made possible by service-ization of curated knowledge artifacts, then injected into a highly scalable backend infrastructure by automated orchestration through public marketplaces. Supplementary examples of client app integration are also provided. Compilation of knowledge into platform-specific form has been left flexible, in so far as implementations comply with ARTAKA’s Context Event Service (CES) communication and Health Services Platform (HSP) Marketplace service packaging standards.
Towards the goal of interoperable human processes, ARTAKA’s treatment of knowledge artifacts as a specialized form of software allows knowledge engineers to operate as a type of software engineering practice. Thus, nearly a century of software development processes, tools, policies, and lessons offer immediate benefit: in some cases, with remarkable parity. Analyses of experimentation is provided with guidelines in how choice aspects of software development life cycles (SDLCs) apply to knowledge artifact development in an ARTAKA environment.
Portions of this culminating document have been further initiated with Standards Developing Organizations (SDOs) intended to ultimately produce normative standards, as have active relationships with other bodies.
ContributorsLee, Preston Victor (Author) / Dinu, Valentin (Thesis advisor) / Sottara, Davide (Committee member) / Greenes, Robert (Committee member) / Arizona State University (Publisher)
Created2018