Physical Sciences and Mathematics Commons^™

Dach1 Mutation Frequency In Endometrial Cancer Is Associated With High Tumor Mutation Burden, Mckayla J. Riggs, Nan Lin, Chi Wang, Dava W. Piecoro, Rachel W. Miller, Oliver A. Hampton, Mahadev Rao, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

OBJECTIVE: DACH1 is a transcriptional repressor and tumor suppressor gene frequently mutated in melanoma, bladder, and prostate cancer. Loss of DACH1 expression is associated with poor prognostic features and reduced overall survival in uterine cancer. In this study, we utilized the Oncology Research Information Exchange Network (ORIEN) Avatar database to determine the frequency of DACH1 mutations in patients with endometrial cancer in our Kentucky population.

METHODS: We obtained clinical and genomic data for 65 patients with endometrial cancer from the Markey Cancer Center (MCC). We examined the clinical attributes of the cancers by DACH1 status by comparing whole-exome sequencing (WES), …

Cellphone Laws And Teens' Calling While Driving: Analysis Of Repeated Cross-Sectional Surveys In 2013, 2015, 2017, And 2019, Li Li, Caitlin N. Pope, Rebecca R. Andridge, Julie K. Bower, Guoqing Hu, Motao Zhu

Graduate Center for Gerontology Faculty Publications

BACKGROUND: Distracted driving among teens is a public health and safety concern. Most states in the U.S. have sought to restrict cellphone use while driving by enacting laws. This study examines the difference in prevalence of self-reported calling while driving (CWD) between states with different cellphone bans.

METHODS: Demographics and CWD data were extracted from state Youth Risk Behavior Surveys (YRBS) from 14 states in 2013, 2015, 2017, and 2019. The state YRBS is conducted every 2 years with a representative sample of 9th through 12th grade students attending public school. States were grouped by type of cellphone law(s): no …

Evidence Of Nickel And Other Trace Elements And Their Relationship To Clinical Findings In Acute Mesoamerican Nephropathy: A Case-Control Analysis, Rebecca S. B. Fischer, Jason M. Unrine, Chandan Vangala, Wayne T. Sanderson, Sreedhar Mandayam, Kristy O. Murray

Plant and Soil Sciences Faculty Publications

BACKGROUND: Although there are several hypothesized etiologies of Mesoamerican Nephropathy (MeN), evidence has not yet pointed to the underlying cause. Exposure to various trace elements can cause the clinical features observed in MeN.

METHODS AND FINDINGS: We measured 15 trace elements, including heavy metals, in renal case-patients (n = 18) and healthy controls (n = 36) in a MeN high-risk region of Nicaragua. Toenails clippings from study participants were analyzed using inductively coupled plasma mass spectrometry. A case-control analysis was performed, and concentrations were also analyzed over participant characteristics and clinical parameters. Nickel (Ni) concentrations were significantly higher in toenails …

Implementation And Sustainment Of A Statewide Telemedicine Diabetic Retinopathy Screening Network For Federally Designated Safety-Net Clinics, Ana Bastos De Carvalho, S. Lee Ware, Feitong Lei, Heather M. Bush, Robert Sprang, Eric B. Higgins

Ophthalmology and Visual Science Faculty Publications

CONTEXT: Diabetic retinopathy (DR) is the leading cause of incident blindness among working-age adults in the United States. Federally designated safety-net clinics (FDSC) often serve as point-of-contact for patients least likely to receive recommended DR screenings, creating opportunity for targeted interventions to increase screening access and compliance.

STUDY DESIGN AND METHODS: With such a goal, we implemented and assessed the longitudinal performance of an FDSC-based telemedicine DR screening (TDRS) network of 22 clinical sites providing nonmydriatic fundus photography with remote interpretation and reporting. Retrospective analysis of patient encounters between February 2014 and January 2019 was performed to assess rates of …

Distinct Clinicopathologic Clusters Of Persons With Tdp-43 Proteinopathy, Yuriko Katsumata, Erin L. Abner, Shama Karanth, Merilee A. Teylan, Charles N. Mock, Matthew D. Cykowski, Edward B. Lee, Kevin L. Boehme, Shubhabrata Mukherjee, John S. K. Kauwe, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Peter T. Nelson

Biostatistics Faculty Publications

To better understand clinical and neuropathological features of TDP-43 proteinopathies, data were analyzed from autopsied research volunteers who were followed in the National Alzheimer’s Coordinating Center (NACC) data set. All subjects (n = 495) had autopsy-proven TDP-43 proteinopathy as an inclusion criterion. Subjects underwent comprehensive longitudinal clinical evaluations yearly for 6.9 years before death on average. We tested whether an unsupervised clustering algorithm could detect coherent groups of TDP-43 immunopositive cases based on age at death and extensive neuropathologic data. Although many of the brains had mixed pathologies, four discernible clusters were identified. Key differentiating features were age at …

Multi-Ancestry Genome-Wide Association Study Accounting For Gene-Psychosocial Factor Interactions Identifies Novel Loci For Blood Pressure Traits, Daokun Sun, Melissa A. Richard, Soloman K. Musani, Yun Ju Sung, Thomas W. Winkler, Karen Schwander, Jin Fang Chai, Xiuqing Guo, Tuomas O. Kilpeläinen, Dina Vojinovic, Hugues Aschard, Traci M. Bartz, Lawrence F. Bielak, Michael R. Brown, Kumaraswamy Chitrala, Fernando P. Hartwig, Andrea R. V. R. Horimoto, Yongmei Liu, Alisa K. Manning, Raymond Noordam, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value < 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A …

Combating Acquired Resistance To Mapk Inhibitors In Melanoma By Targeting Abl1/2-Mediated Reactivation Of Mek/Erk/Myc Signaling, Rakshamani Tripathi, Zulong Liu, Aditi Jain, Anastasia Lyon, Christina Meeks, Dana Richards, Jinpeng Liu, Daheng He, Chi Wang, Marika Nespi, Andrey Rymar, Peng Wang, Melissa Wilson, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

Metastatic melanoma remains an incurable disease for many patients due to the limited success of targeted and immunotherapies. BRAF and MEK inhibitors reduce metastatic burden for patients with melanomas harboring BRAF mutations; however, most eventually relapse due to acquired resistance. Here, we demonstrate that ABL1/2 kinase activities and/or expression are potentiated in cell lines and patient samples following resistance, and ABL1/2 drive BRAF and BRAF/MEK inhibitor resistance by inducing reactivation of MEK/ERK/MYC signaling. Silencing/inhibiting ABL1/2 blocks pathway reactivation, and resensitizes resistant cells to BRAF/MEK inhibitors, whereas expression of constitutively active ABL1/2 is sufficient to promote resistance. Significantly, nilotinib (2nd generation …

Age-Related Losses In Cardiac Autonomic Activity During A Daytime Nap, Pin-Chun Chen, Negin Sattari, Lauren N. Whitehurst, Sara C. Mednick

Psychology Faculty Publications

In healthy, young individuals, a reduction in cardiovascular output and a shift from sympathetic to parasympathetic (vagal) dominance is observed from wake into stages of nocturnal and daytime sleep. This cardiac autonomic profile, measured by heart rate variability (HRV), has been associated with significant benefits for cardiovascular health. Aging is associated with decreased nighttime sleep quality and lower parasympathetic activity during both sleep and resting. However, it is not known whether age-related dampening of HRV extends to daytime sleep, diminishing the cardiovascular benefits of naps in the elderly. Here, we investigated this question by comparing the autonomic activity profile between …

Considerations For Studying Sex As A Biological Variable In Spinal Cord Injury, Andrew N. Stewart, Steven M. Maclean, Arnold J. Stromberg, Jessica P. Whelan, William M. Bailey, John C. Gensel, Melinda E. Wilson

Physiology Faculty Publications

In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of …

Nanoceria Distribution And Effects Are Mouse-Strain Dependent, Robert A. Yokel, Michael T. Tseng, D. Allan Butterfield, Matthew L. Hancock, Eric A. Grulke, Jason M. Unrine, Arnold J. Stromberg, Alan K. Dozier, Uschi M. Graham

Pharmaceutical Sciences Faculty Publications

Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. Objective: Assess nanoceria (cerium oxide, CeO₂ nanoparticle) uptake time course and organ distribution, cellular and oxidative stress, and bioprocessing as a function of mouse strain. Methods: C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. Organs were collected for cerium analysis; light and electron microscopy with elemental mapping; and protein carbonyl, IL-1β, and caspase-1 determination. Results: Peripheral organ cerium significantly increased, generally more …

Heart Failure In Humans Reduces Contractile Force In Myocardium From Both Ventricles, Cheavar A. Blair, Elizabeth A Brundage, Katherine L. Thompson, Arnold J. Stromberg, Maya Guglin, Brandon J Biesiadecki, Kenneth S. Campbell

Statistics Faculty Publications

This study measured how heart failure affects the contractile properties of the human myocardium from the left and right ventricles. The data showed that maximum force and maximum power were reduced by approximately 30% in multicellular preparations from both ventricles, possibly because of ventricular remodeling (e.g., cellular disarray and/or excess fibrosis). Heart failure increased the calcium (Ca²⁺) sensitivity of contraction in both ventricles, but the effect was bigger in right ventricular samples. The changes in Ca²⁺ sensitivity were associated with ventricle-specific changes in the phosphorylation of troponin I, which indicated that adrenergic stimulation might induce different effects …

Spermine Synthase And Myc Cooperate To Maintain Colorectal Cancer Cell Survival By Repressing Bim Expression, Yubin Guo, Qing Ye, Pan Deng, Yanan Cao, Daheng He, Zhaohe Zhou, Chi Wang, Yekaterina Y. Zaytseva, Charles E. Schwartz, Eun Young Lee, B. Mark Evers, Andrew J. Morris, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC), but the underlying mechanism is incompletely characterized. Here, we report that spermine synthase (SMS), a polyamine biosynthetic enzyme, is overexpressed in CRC. Targeted disruption of SMS in CRC cells results in spermidine accumulation, which inhibits FOXO3a acetylation and allows subsequent translocation to the nucleus to transcriptionally induce expression of the proapoptotic protein Bim. However, this induction is blunted by MYC-driven expression of miR-19a and miR-19b that repress Bim production. Pharmacological or genetic inhibition of MYC activity in SMS-depleted CRC cells dramatically induces Bim expression and apoptosis …

A Web-Based, Positive Emotion Skills Intervention For Enhancing Posttreatment Psychological Well-Being In Young Adult Cancer Survivors (Empower): Protocol For A Single-Arm Feasibility Trial, John M. Salsman, Laurie E. Mclouth, Michael Cohn, Janet A. Tooze, Mia Sorkin, Judith T. Moskowitz

Behavioral Science Faculty Publications

BACKGROUND: Adolescent and young adult cancer survivors (AYAs) experience clinically significant distress and have limited access to supportive care services. Interventions to enhance psychological well-being have improved positive affect and reduced depression in clinical and healthy populations but have not been routinely tested in AYAs.

OBJECTIVE: The aim of this protocol is to (1) test the feasibility and acceptability of a Web-based positive emotion skills intervention for posttreatment AYAs called Enhancing Management of Psychological Outcomes With Emotion Regulation (EMPOWER) and (2) examine proof of concept for reducing psychological distress and enhancing psychological well-being.

METHODS: The intervention development and testing are …

Brain Structure Changes Over Time In Normal And Mildly Impaired Aged Persons, Charles D. Smith, Linda J. Van Eldik, Gregory A. Jicha, Frederick A. Schmitt, Peter T. Nelson, Erin L. Abner, Richard J. Kryscio, Richard R. Murphy, Anders H. Andersen

Neurology Faculty Publications

Structural brain changes in aging are known to occur even in the absence of dementia, but the magnitudes and regions involved vary between studies. To further characterize these changes, we analyzed paired MRI images acquired with identical protocols and scanner over a median 5.8-year interval. The normal study group comprised 78 elders (25M 53F, baseline age range 70-78 years) who underwent an annual standardized expert assessment of cognition and health and who maintained normal cognition for the duration of the study. We found a longitudinal grey matter (GM) loss rate of 2.56 ± 0.07 ml/year (0.20 ± 0.04%/year) and a …

Dot: Gene-Set Analysis By Combining Decorrelated Association Statistics, Olga A. Vsevolozhskaya, Min Shi, Fengjiao Hu, Dmitri V. Zaykin

Biostatistics Faculty Publications

Historically, the majority of statistical association methods have been designed assuming availability of SNP-level information. However, modern genetic and sequencing data present new challenges to access and sharing of genotype-phenotype datasets, including cost of management, difficulties in consolidation of records across research groups, etc. These issues make methods based on SNP-level summary statistics particularly appealing. The most common form of combining statistics is a sum of SNP-level squared scores, possibly weighted, as in burden tests for rare variants. The overall significance of the resulting statistic is evaluated using its distribution under the null hypothesis. Here, we demonstrate that this basic …

Using Medical Claims Database To Develop A Population Disease Progression Model For Leuprorelin-Treated Subjects With Hormone-Sensitive Prostate Cancer, Yixuan Zou, Fei Tang, Jeffery C. Talbert, Chee M. Ng

Pharmacy Practice and Science Faculty Publications

Androgen deprivation therapy (ADT) is a widely used treatment for patients with hormone-sensitive prostate cancer (PCa). However, duration of treatment response varies, and most patients eventually experience disease progression despite treatment. Leuprorelin is a luteinizing hormone-releasing hormone (LHRH) agonist, a commonly used form of ADT. Prostate-specific antigen (PSA) is a biomarker for monitoring disease progression and predicting treatment response and survival in PCa. However, time-dependent profile of tumor regression and growth in patients with hormone-sensitive PCa on ADT has never been fully characterized. In this analysis, nationwide medical claims database provided by Humana from 2007 to 2011 was used to …

Comparison Of Upper Extremity Function In Women With And Women Without A History Of Breast Cancer, Mary Insana Fisher, Gilson J. Capilouto, Terry Malone, Heather M. Bush, Timothy L. Uhl

Communication Sciences and Disorders Faculty Publications

Background

Breast cancer treatments often result in upper extremity functional limitations in both the short and long term. Current evidence makes comparisons against a baseline or contralateral limb, but does not consider changes in function associated with aging.

Objective

The objective of this study was to compare upper extremity function between women treated for breast cancer more than 12 months in the past and women without cancer.

Design

This was an observational cross-sectional study.

Methods

Women who were diagnosed with breast cancer and had a mean post-surgical treatment time of 51 months (range = 12–336 months) were compared with women …

Hierarchical Clustering Analyses Of Plasma Proteins In Subjects With Cardiovascular Risk Factors Identify Informative Subsets Based On Differential Levels Of Angiogenic And Inflammatory Biomarkers, Zachary Winder, Tiffany L. Sudduth, David W. Fardo, Qiang Cheng, Larry B. Goldstein, Peter T. Nelson, Frederick A. Schmitt, Gregory A. Jicha, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Agglomerative hierarchical clustering analysis (HCA) is a commonly used unsupervised machine learning approach for identifying informative natural clusters of observations. HCA is performed by calculating a pairwise dissimilarity matrix and then clustering similar observations until all observations are grouped within a cluster. Verifying the empirical clusters produced by HCA is complex and not well studied in biomedical applications. Here, we demonstrate the comparability of a novel HCA technique with one that was used in previous biomedical applications while applying both techniques to plasma angiogenic (FGF, FLT, PIGF, Tie-2, VEGF, VEGF-D) and inflammatory (MMP1, MMP3, MMP9, IL8, TNFα) protein data to …

Mentoring Multi-College Bystander Efficacy Evaluation – An Approach To Growing The Next Generation Of Gender-Based Interpersonal Violence Intervention And Prevention (Vip) Researchers, Ann L. Coker, Danielle Davidov, Heather M. Bush, Emily R. Clear

Obstetrics and Gynecology Faculty Publications

The Centers for Disease Control and Prevention provided funding (U01 CE002668) to evaluate bystander program efficacy to reduce gender-based violence on college campuses (Aim 1) and to create a mentoring network (Aim 2) for young campus-based researchers interested in violence intervention or prevention (VIP). While an evaluation of this mentoring program is ongoing, our purpose here was to document the strategies used to create, implement, and begin evaluation of this national multi-college mentoring network. As each public college was recruited into this evaluation named multi-college Bystander Efficacy Evaluation (mcBEE), each college was invited to nominate a researcher interested in receiving …

Hypercholesterolemia Accelerates Both The Initiation And Progression Of Angiotensin Ii-Induced Abdominal Aortic Aneurysms, Jing Liu, Hisashi Sawada, Deborah A. Howatt, Jessica J. Moorleghen, Olga A. Vsevolozhskaya, Alan Daugherty, Hong S. Lu

Pharmacology and Nutritional Sciences Faculty Publications

Objective: This study determined whether hypercholesterolemia would contribute to both the initiation and progression of angiotensin (Ang)II-induced abdominal aortic aneurysms (AAAs) in mice.

Methods and Results: To determine whether hypercholesterolemia accelerates the initiation of AAAs, male low-density lipoprotein (LDL) receptor -/- mice were either fed one week of Western diet prior to starting AngII infusion or initiated Western diet one week after starting AngII infusion. During the first week of AngII infusion, mice fed normal diet had less luminal expansion of the suprarenal aorta compared to those initiated Western diet after the first week of AngII infusion. The two groups …

Orthogonal Recurrent Neural Networks And Batch Normalization In Deep Neural Networks, Kyle Eric Helfrich

Theses and Dissertations--Mathematics

Despite the recent success of various machine learning techniques, there are still numerous obstacles that must be overcome. One obstacle is known as the vanishing/exploding gradient problem. This problem refers to gradients that either become zero or unbounded. This is a well known problem that commonly occurs in Recurrent Neural Networks (RNNs). In this work we describe how this problem can be mitigated, establish three different architectures that are designed to avoid this issue, and derive update schemes for each architecture. Another portion of this work focuses on the often used technique of batch normalization. Although found to be successful …

Sample Size Calculation And Blinded Recalculation For Analysis Of Covariance Models With Multiple Random Covariates, Georg Zimmermann, Meinhard Kieser, Arne C. Bathke

Statistics Faculty Publications

When testing for superiority in a parallel-group setting with a continuous outcome, adjusting for covariates is usually recommended. For this purpose, the analysis of covariance is frequently used, and recently several exact and approximate sample size calculation procedures have been proposed. However, in case of multiple covariates, the planning might pose some practical challenges and pitfalls. Therefore, we propose a method, which allows for blinded re-estimation of the sample size during the course of the trial. Simulations confirm that the proposed method provides reliable results in many practically relevant situations, and applicability is illustrated by a real-life data example.

Nonparametric Tests Of Lack Of Fit For Multivariate Data, Yan Xu

Theses and Dissertations--Statistics

A common problem in regression analysis (linear or nonlinear) is assessing the lack-of-fit. Existing methods make parametric or semi-parametric assumptions to model the conditional mean or covariance matrices. In this dissertation, we propose fully nonparametric methods that make only additive error assumptions. Our nonparametric approach relies on ideas from nonparametric smoothing to reduce the test of association (lack-of-fit) problem into a nonparametric multivariate analysis of variance. A major problem that arises in this approach is that the key assumptions of independence and constant covariance matrix among the groups will be violated. As a result, the standard asymptotic theory is not …

Algebraic And Geometric Properties Of Hierarchical Models, Aida Maraj

Theses and Dissertations--Mathematics

In this dissertation filtrations of ideals arising from hierarchical models in statistics related by a group action are are studied. These filtrations lead to ideals in polynomial rings in infinitely many variables, which require innovative tools. Regular languages and finite automata are used to prove and explicitly compute the rationality of some multivariate power series that record important quantitative information about the ideals. Some work regarding Markov bases for non-reducible models is shown, together with advances in the polyhedral geometry of binary hierarchical models.

Unitary And Symmetric Structure In Deep Neural Networks, Kehelwala Dewage Gayan Maduranga

Theses and Dissertations--Mathematics

Recurrent neural networks (RNNs) have been successfully used on a wide range of sequential data problems. A well-known difficulty in using RNNs is the vanishing or exploding gradient problem. Recently, there have been several different RNN architectures that try to mitigate this issue by maintaining an orthogonal or unitary recurrent weight matrix. One such architecture is the scaled Cayley orthogonal recurrent neural network (scoRNN), which parameterizes the orthogonal recurrent weight matrix through a scaled Cayley transform. This parametrization contains a diagonal scaling matrix consisting of positive or negative one entries that can not be optimized by gradient descent. Thus the …

Measuring Variability In Model Performance Measures, Matthew Rutledge

Theses and Dissertations--Statistics

As data become increasingly available, statisticians are confronted with both larger sample sizes and larger numbers of predictors. While both of these factors are beneficial in building better predictive models and allowing for better inference, models can become difficult to interpret and often include variables of little practical significance. This dissertation provides methods that assist model builders to better understand and select from a collection of candidate models. We study the asymptotic distribution of AIC and propose a graphical tool to assist practitioners in comparing and contrasting candidate models. Real-world examples show how this graphic might be used and a …

Nonparametric Analysis Of Clustered And Multivariate Data, Yue Cui

Theses and Dissertations--Statistics

In this dissertation, we investigate three distinct but interrelated problems for nonparametric analysis of clustered data and multivariate data in pre-post factorial design.

In the first project, we propose a nonparametric approach for one-sample clustered data in pre-post intervention design. In particular, we consider the situation where for some clusters all members are only observed at either pre or post intervention but not both. This type of clustered data is referred to us as partially complete clustered data. Unlike most of its parametric counterparts, we do not assume specific models for data distributions, intra-cluster dependence structure or variability, in effect …

Cancer Phylogenetic Analysis Based On Rna-Seq Data, Tingting Zhai

Theses and Dissertations--Statistics

Studying tumor evolution is a major task to understand the biological mechanism of carcinogenesis, develop new cancer therapies, and prevent drug resistance. We focus on two important questions in tumor evolution. The first question is to quantify intra-tumor heterogeneity, where multiple subclones of tumor cells with distinct transcriptomic profiles. Another question is to estimate the temporal order of alteration of key cancer pathways during tumor evolution. We present a new statistical method to 1) reconstruct the evolutionary history and population frequency of the subclonal lineages of tumor cells and 2) infer temporal order of pathway alterations in tumor evolution for …

Semiparametric And Nonparametric Methods For Comparing Biomarker Levels Between Groups, Yuntong Li

Theses and Dissertations--Statistics

Comparing the distribution of biomarker measurements between two groups under either an unpaired or paired design is a common goal in many biomarker studies. However, analyzing biomarker data is sometimes challenging because the data may not be normally distributed and contain a large fraction of zero values or missing values. Although several statistical methods have been proposed, they either require data normality assumption, or are inefficient. We proposed a novel two-part semiparametric method for data under an unpaired setting and a nonparametric method for data under a paired setting. The semiparametric method considers a two-part model, a logistic regression for …

Bayesian Kinetic Modeling For Tracer-Based Metabolomic Data, Xu Zhang

Theses and Dissertations--Statistics

Kinetic modeling of the time dependence of metabolite concentrations including the unstable isotope labeled species is an important approach to simulate metabolic pathway dynamics. It is also essential for quantitative metabolic flux analysis using tracer data. However, as the metabolic networks are complex including extensive compartmentation and interconnections, the parameter estimation for enzymes that catalyze individual reactions needed for kinetic modeling is challenging. As the pa- rameter space is large and multi-dimensional while kinetic data are comparatively sparse, the estimation procedure (especially the point estimation methods) often en- counters multiple local maximum such that standard maximum likelihood methods may yield …