Statistics and Probability Commons^™

A Novel Pathway-Based Distance Score Enhances Assessment Of Disease Heterogeneity In Gene Expression, Yunqing Liu, Xiting Yan

Yale Day of Data

Distance-based unsupervised clustering of gene expression data is commonly used to identify heterogeneity in biologic samples. However, high noise levels in gene expression data and the relatively high correlation between genes are often encountered, so traditional distances such as Euclidean distance may not be effective at discriminating the biological differences between samples. In this study, we developed a novel computational method to assess the biological differences based on pathways by assuming that ontologically defined biological pathways in biologically similar samples have similar behavior. Application of this distance score results in more accurate, robust, and biologically meaningful clustering results in both …

How Can The Final Goal Of Completely Replacing Animal Procedures Successfully Be Achieved?, Christiane Baumgartl-Simons, Christiane Hohense

Validation of Alternative Methods Collection

Article 23 of European Union (EU) Directive 86/609/EEC required that Member States promote the development and validation of alternative technologies and stated that the European Commission (EC) “shall report before the end of 1987 on the possibility of modifying tests and guidelines” (European Parliament, 1986, Article 23). This Directive was replaced by Directive 2010/63/EU on the protection of animals used for scientific purposes, which now requires that Member States develop and validate alternative approaches much more precisely and specifies that the ultimate objective is the “full replacement of procedures on live animals for scientific and educational purposes, as soon as …

How To Evaluate The Science Of Non-Human Animal Use In Biomedical Research And Testing: A Proposed Format For Debate, Ray Greek, Lisa A. Kramer

Validation of Alternative Methods Collection

Over time, the interpretation of science has occasionally been corrupted by vested interest groups, be they financially motivated or ego driven. Scientific consensus and widespread public beliefs usually catch up with the evidence, but this can take a very long time and often costs lives. The use of non-human animals in biomedical research and testing is a scientific endeavor and, as such, can and should be evaluated in light of the best science currently available. But facts that have been accepted in all areas of science are routinely ignored or called into question by well-funded, vested interest groups, compromising the …

Extrapolation Of Animal Research Data To Humans: An Analysis Of The Evidence, Rebecca Ram

Validation of Animal Experimentation Collection

The ethical arguments against animal experimentation remain ever-strong. In addition, the scientific case against the use of animals in research grows more compelling, with exponential progress in the development of alternative methods and new research technologies. The Dutch authorities recently announced an ambitious, but welcome, proposal to phase out “the use of laboratory animals in regulatory safety testing of chemicals, food ingredients, pesticides and (veterinary) medicines” by 2025, as well as “the use of laboratory animals for the release of biological products, such as vaccines” (Netherlands National Committee for the protection of animals used for scientific purposes, NCad, 2016, p. …

Replacing Animal Tests To Improve Safety For Humans, Kathy Archibald, Robert Coleman, Tamara Drake

Application of Alternative Methods Collection

In this chapter, we propose a new, pragmatic approach that could accelerate the replacement of most, if not all, regulatory animal tests with superior tests based on human biology. We also propose that changes to the requirements for safety testing, issued by the us Food and Drug Administration (fda), must be made in order to enable the use of superior new tests, which are currently disadvantaged by the outdated language of the regulations. But first, it is imperative to establish some level of understanding of the efficacy of existing animal-based methods in order to know whether any possible replacement is …

The Changing Paradigm In Preclinical Toxicology: In Vitro And In Silico Methods In Liver Toxicity Evaluations, Fozia Noor

Application of Alternative Methods Collection

In vitro methods, based on human primary cells, cell lines, and genetically modified reporter cell lines, have greatly expanded the scope of in vitro toxicology. Other significant progress in the area of human-induced pluripotent stem cells (hiPSCs) (Asgari et al., 2010; Schwartz et al., 2014; Shinde et al., 2016; Shtrichman, Germanguz and Itskovitz-Eldor, 2013) is allowing the application of patient and disease-specific hiPSCs (Ghodsizadeh et al., 2010; McCracken et al., 2014; Siller et al., 2013). Moreover, the tools of precise genome editing with engineered nucleases, such as the zinc finger nucleases (zfns), the transcription activator-like effecter nucleases (talens) and, more …

The Potential Of Organ On Chip Technology For Replacing Animal Testing, Malcolm Wilkinson

Human Clinical Trials Collection

The term organ on a chip is used to describe the latest stage of development of in vitro cell culture technology. Figure 26.1 shows its steady development since the 1960s. Each step forward has improved our ability to model human-clinical response to new drugs or therapies and has enabled safety risk assessment of existing cosmetics, personal care products, or other chemicals in the environment. Scientific evidence that the predictive power of in vitro tests is superior to the use of animals will trigger a major shift in the way that medical research, in many areas, is carried out. In this …

Recent Developments In Alternatives To Animal Testing, Katy Taylor

Application of Alternative Methods Collection

Methods that replace techniques that use live animals, or methods of testing substances without live animal use, are known as alternatives, replacements or non-animal methods. Some prefer the term advanced technologies given the fact that they often rely on more sophisticated technology and are more human- relevant than the animal test they replace (see Langley et al., 2015). There have been efforts to replace animal tests since the 1960s. Significant progress initially came in replacing animals used to diagnose human disease; to produce biological drugs (such as vaccines); and to safety test batches of these drugs as they were produced. …

The Correlation Between Sleep And Lifespan In Drosophila Melanogaster, Joshua Randall Lisse

Masters Theses

”Adequate sleep is associated with an individual’s health. Too little sleep is associated with many health problems, including cardiovascular disease, obesity, and a general increase in all-cause mortality. Yet the molecular changes that link poor sleep and changes in health are still not well understood. Individuals have a unique daily need for sleep, and deviations from the animal’s regular sleeping patterns can be indicative of, or result in, underlying changes in its health. Therefore, we hypothesize that changes in the sleep architecture in Drosophila melanogaster reflect changes in the fly’s health.

We determined sleep architecture in wild-type male flies over …

Methods For Estimating Mountain Goat Occupancy And Abundance, Molly Mcdevitt

Graduate Student Theses, Dissertations, & Professional Papers

Abundance and occupancy are two parameters of central interest to the field of ecology. Furthermore, accurate (both precise and unbiased) estimates are key pieces to the puzzle of effective wildlife management decision-making. While there exist a variety of sampling techniques and statistical models for effectively estimating population parameters for frequently encountered and large mammals, methods for sampling unmarked and rare species are few and far between. The first step to acquiring usable parameter estimates is through the use of sampling theory and incorporation of probabilistic sampling designs to collect count-data and occurrence-data. Often, it is assumed that probabilistic sampling designs …

Spatiotemporal Dynamics Of Nitrogen And Carbon Biogeochemistry In A Wetland-Stream Sequence, Patrick E. Hurley

Graduate Student Theses, Dissertations, & Professional Papers

Studies of aquatic ecosystems often segregate streams from the influential ponds, lakes, and wetland zones that act as important transitions between terrestrial and fluvial systems. Across the aquatic landscape, these zones interact to form linked ecosystems that function as discrete nutrient processing domains, shifting biogeochemical signals due to spatial and temporal variability in hydrologic and biologic controls. Using a mass-balance approach, we profiled nutrient dynamics along a 23-km wetland-stream sequence over three seasons. Hydrologic, morphologic, and biologic conditions, as well as landscape attributes, were quantified to determine potential controls on biogeochemical cycling in a tributary of the Upper Clark Fork …

The Role Of Glucose Level On The Performance Of The Framingham Risk Score, Uohna June Thiessen

Walden Dissertations and Doctoral Studies

Cardiovascular diseases (CVD) are responsible for more deaths than any other disease, continue to threaten the quality of life for many, and is a major burden to the health care system. The Framingham Heart Study (FHS) identified the major CVD risk factors that became essential to effective CVD screening strategies and the Framingham Risk Score (FRS), is used to assess CVD risk. Based on the concepts of the health behavior model and CVD as a cardiometabolic disorder, multivariate logistic regression analysis was used to evaluate the association between fasting blood glucose (FBG) levels and a CHD event, and to determine …

Measuring Trace Element Concentrations In Artiodactyl Cannonbones Using Portable X-Ray Fluorescence, Joshua L. Henderson

All Master's Theses

Artiodactyl bones are the most common faunal remains found in Washington prehistoric archaeology sites, but they are often too fragmented to accurately identify a family, genus, or species. Traditional faunal analysis can only organize unidentifiable bone fragments into size class, and chemical methods often require the destruction of bone samples. In this thesis research, I tested a new, nondestructive faunal analysis technique using portable X-ray fluorescence (pXRF) to measure trace element concentrations in comparative collection and archaeological bone samples. Using cannonbones from five different artiodactyl species, I collected trace element data from 50 comparative collection specimens and 18 archaeological specimens …

The Effect Of Neonicotinoids On Apis Mellifera: A Revisit, Qingchen Liang

Master's Theses and Doctoral Dissertations

Colony collapse disorder (CCD), which has caused high colony mortality rates in the European honeybee (Apis mellifera), is a pressing economical and ecological problem. I revisited Woodcock et al.'s (2017a) paper, "Country-specic Effects of Neonicotinoid Pesticides on Honey Bees and Wild Bees", in light of unsound statistical methods used in the original study. In the first part of this paper, I attempted to replicate the analysis underlying key findings in the original paper. In the second part, I reanalyzed the data using mostly non-parametric methods in order to obtain robust results. I did not find any evidence for a harmful …

The Effect Of Maternal Dietary Habits During Pregnancy On Neonate Leptin Methylation Patterns And Gestational Age, Sean Fitzpatrick

Legacy Theses & Dissertations (2009 - 2024)

The health of a newborn baby is inextricably linked to the health status of its mother and in turn the mother’s diet during pregnancy. Leptin (LEP) is an adipokine hormone involved in metabolism regulation and has been linked fetal development through the hypothalamic-pituitary-adrenal axis (HPA). Prior work suggests that gestational epigenetic alterations the LEP gene may be sensitive to adverse exposures during pregnancy, which in turn could explain variation in neonate outcomes. However, no prior work has examined this possibility explicitly. The objective of this study was to investigate the association between dietary patterns of mothers during pregnancy and their …

Combination Of Resampling Based Lasso Feature Selection And Ensembles Of Regularized Regression Models, Abhijeet R. Patil

Open Access Theses & Dissertations

In high-dimensional data, the performance of various classiers is largely dependent on the selection of important features. Most of the individual classiers using existing feature selection (FS) methods do not perform well for highly correlated data. Obtaining important

features using the FS method and selecting the best performing classier is a challenging task in high throughput data. In this research, we propose a combination of resampling based least absolute shrinkage and selection operator (LASSO) feature selection (RLFS)

and ensembles of regularized regression models (ERRM) capable of handling data with the high correlation structures. The ERRM boosts the prediction accuracy with …

The Effect Of Vegetative Structure On Nest-Burrow Selection By The Western Burrowing Owl: Comparing Traditional Methods To Photogrammetry With An Unmanned Aerial System, Dylan J. Steffen

Master's Theses or Doctor of Nursing Practice

The shortgrass prairie ecoregion in the United States has been reduced to 52% of its historical extent, contributing to reduced habitat for native species. One such species is the Burrowing Owl (Athene cunicularia). The Western Burrowing Owl subspecies (A. c. hypugaea) is listed as a Species of Special Concern in nearly every western and midwestern state, including Kansas where it is designated as a Tier II Species of Greatest Conservation Need. Habitat destruction due to conversion to cropland, increasing use of pesticides, and reduction in burrowing mammal abundance are the primary threats that have led to …

Applying Machine Learning Algorithms For The Analysis Of Biological Sequences And Medical Records, Shaopeng Gu

Electronic Theses and Dissertations

The modern sequencing technology revolutionizes the genomic research and triggers explosive growth of DNA, RNA, and protein sequences. How to infer the structure and function from biological sequences is a fundamentally important task in genomics and proteomics fields. With the development of statistical and machine learning methods, an integrated and user-friendly tool containing the state-of-the-art data mining methods are needed. Here, we propose SeqFea-Learn, a comprehensive Python pipeline that integrating multiple steps: feature extraction, dimensionality reduction, feature selection, predicting model constructions based on machine learning and deep learning approaches to analyze sequences. We used enhancers, RNA N6- methyladenosine sites and …

Lack Of Vaccination Risks, Abigail Sebunia

Williams Honors College, Honors Research Projects

This paper is a study regarding how vaccination rates are related to the number of measles cases that occur in a particular state. First, I will review the history of vaccines and the motivations for the refusals of this medical procedure. In addition, I will examine the various regulations regarding vaccinations and which states allow non-medical exemptions for religious or personal reasons. Within my analysis, I will provide examples of recent outbreaks to represent the extent of this current dilemma. Furthermore, I will offer potential solutions to mitigate measles outbreaks and the science regarding Herd Immunity Thresholds (HIT) to limit …

Microarray Data Analysis And Classification Of Cancers, Grant Gates

Williams Honors College, Honors Research Projects

When it comes to cancer, there is no standardized approach for identifying new cancer classes nor is there a standardized approach for assigning cancer tumors to existing classes. These two ideas are known as class discovery and class prediction. For a cancer patient to receive proper treatment, it is important that the type of cancer be accurately identified. For my Senior Honors Project, I would like to use this opportunity to research a topic in bioinformatics. Bioinformatics incorporates a few different subjects into one including biology, computer science and statistics. An intricate method for class discovery and class prediction is …

Automatic 13C Chemical Shift Reference Correction Of Protein Nmr Spectral Data Using Data Mining And Bayesian Statistical Modeling, Xi Chen

Theses and Dissertations--Molecular and Cellular Biochemistry

Nuclear magnetic resonance (NMR) is a highly versatile analytical technique for studying molecular configuration, conformation, and dynamics, especially of biomacromolecules such as proteins. However, due to the intrinsic properties of NMR experiments, results from the NMR instruments require a refencing step before the down-the-line analysis. Poor chemical shift referencing, especially for ¹³C in protein Nuclear Magnetic Resonance (NMR) experiments, fundamentally limits and even prevents effective study of biomacromolecules via NMR. There is no available method that can rereference carbon chemical shifts from protein NMR without secondary experimental information such as structure or resonance assignment.

To solve this problem, we …

Adult Atlantic Sturgeon Population Dynamics In The York River, Virginia, Jason E. Kahn

Graduate Theses, Dissertations, and Problem Reports (ETD)

Sturgeon first appear in the fossil record in the Triassic Period just over 200 million years ago and are among the most primitive of the bony fishes. Despite their large size and historic presence along the East Coast, Atlantic sturgeon were not targeted for their meat and caviar as a commercial fishery until 1880. By 1905 they had declined to less than one percent of their pre-fishing abundance but the fishery continued. Prior to 1980, there had been very little research on Atlantic sturgeon, primarily limited to documenting landing location and poundage, maximum longevity, or weight of eggs per fish. …

Compound-Specific Isotope Analysis Of Amino Acids In Biological Tissues: Applications In Forensic Entomology, Food Authentication And Soft-Biometrics In Humans, Mayara Patricia Viana De Matos

Graduate Theses, Dissertations, and Problem Reports (ETD)

In this work we demonstrate the power of compound-specific isotope analysis (CSIA) to analyze proteinaceous biological materials in three distinct forensic applications, including: 1) linking necrophagous blow flies in different life stages to their primary carrion diet; 2) identifying the harvesting area of oysters for food authentication purposes; and 3) the ability to predict biometric traits about humans from their hair.

In the first application, we measured the amino-acid-level fractionation that occurs at each major life stage of Calliphora vicina (Robineau-Desvoidy) (Diptera: Calliphoridae) blow flies. Adult blow flies oviposited on raw pork muscle, beef muscle, or chicken liver. Larvae, pupae …

Methods For Joint Normalization And Comparison Of Hi-C Data, John C. Stansfield

Theses and Dissertations

The development of chromatin conformation capture technology has opened new avenues of study into the 3D structure and function of the genome. Chromatin structure is known to influence gene regulation, and differences in structure are now emerging as a mechanism of regulation between, e.g., cell differentiation and disease vs. normal states. Hi-C sequencing technology now provides a way to study the 3D interactions of the chromatin over the whole genome. However, like all sequencing technologies, Hi-C suffers from several forms of bias stemming from both the technology and the DNA sequence itself. Several normalization methods have been developed for normalizing …

Latent Growth Model Approach To Characterize Maternal Prenatal Dna Methylation Trajectories, Dana Lapato

Theses and Dissertations

Background. DNA methylation (DNAm) is a removable chemical modification to the DNA sequence intimately associated with genomic stability, cellular identity, and gene expression. DNAm patterning reflects joint contributions from genetic, environmental, and behavioral factors. As such, differences in DNAm patterns may explain interindividual variability in risk liability for complex traits like major depression (MD). Hundreds of significant DNAm loci have been identified using cross-sectional association studies. This dissertation builds on that foundational work to explore novel statistical approaches for longitudinal DNAm analyses. Methods. Repeated measures of genome-wide DNAm and social and environmental determinants of health were collected up to six …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

Statistical Methods For Joint Analysis Of Multiple Phenotypes And Their Applications For Phewas, Xueling Li

Dissertations, Master's Theses and Master's Reports

Genome-wide association studies (GWAS) have successfully detected tens of thousands of robust SNP-trait associations. Earlier researches have primarily focused on association studies of genetic variants and some well-defined functions or phenotypic traits. Emerging evidence suggests that pleiotropy, the phenomenon of one genetic variant affects multiple phenotypes, is widespread, especially in complex human diseases. Therefore, individual phenotype analyses may lose statistical power to identify the underlying genetic mechanism. Contrasting with single phenotype analyses, joint analysis of multiple phenotypes exploits the correlations between phenotypes and aggregates multiple weak marginal effects and is therefore likely to provide new insights into the functional consequences …

Colloidal And Truly Dissolved Metal(Loid)S In Wastewater Lagoons And Their Removal With Floating Treatment Wetlands, Lauren Sullivan

Graduate Student Theses, Dissertations, & Professional Papers

Climate change is predicted to cause continuing declines in late-season streamflow, thus increasing the relative contribution of wastewater effluent to surface water flows. Wastewater effluent represents a critical point source of metal and metalloid contamination to aquatic ecosystems and wastewater lagoons are the most common wastewater treatment system in the rural United States. Although the fraction of total wastewater metals and metalloids in "dissolved" forms (defined here asnm) likely drives the potential for negative effects on receiving waters, this broad operational definition lumps truly dissolved solutes (nm) with small colloids and nanomaterials (1-450 nm; hereafter colloids). This size distinction may …

Power In Pairs: Assessing The Statistical Value Of Paired Samples In Tests For Differential Expression, John R. Stevens, Jennifer S. Herrick, Roger K. Wolff, Martha L. Slattery

Mathematics and Statistics Faculty Publications

Background: When genomics researchers design a high-throughput study to test for differential expression, some biological systems and research questions provide opportunities to use paired samples from subjects, and researchers can plan for a certain proportion of subjects to have paired samples. We consider the effect of this paired samples proportion on the statistical power of the study, using characteristics of both count (RNA-Seq) and continuous (microarray) expression data from a colorectal cancer study.

Results: We demonstrate that a higher proportion of subjects with paired samples yields higher statistical power, for various total numbers of samples, and for various strengths of …

Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser

Internal Medicine Faculty Publications

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related …