Matching Items (16)
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- All Subjects: Cancer
- All Subjects: artificial intelligence
- Creators: School of Mathematical and Statistical Sciences
- Resource Type: Text
Description
Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and includes chemotherapy, radiation therapy, and surgical removal if the tumor is surgically accessible. Treatment seldom results in a significant increase in longevity, partly due to the lack of precise information regarding tumor size and location. This lack of information arises from the physical limitations of MR and CT imaging coupled with the diffusive nature of glioblastoma tumors. GBM tumor cells can migrate far beyond the visible boundaries of the tumor and will result in a recurring tumor if not killed or removed. Since medical images are the only readily available information about the tumor, we aim to improve mathematical models of tumor growth to better estimate the missing information. Particularly, we investigate the effect of random variation in tumor cell behavior (anisotropy) using stochastic parameterizations of an established proliferation-diffusion model of tumor growth. To evaluate the performance of our mathematical model, we use MR images from an animal model consisting of Murine GL261 tumors implanted in immunocompetent mice, which provides consistency in tumor initiation and location, immune response, genetic variation, and treatment. Compared to non-stochastic simulations, stochastic simulations showed improved volume accuracy when proliferation variability was high, but diffusion variability was found to only marginally affect tumor volume estimates. Neither proliferation nor diffusion variability significantly affected the spatial distribution accuracy of the simulations. While certain cases of stochastic parameterizations improved volume accuracy, they failed to significantly improve simulation accuracy overall. Both the non-stochastic and stochastic simulations failed to achieve over 75% spatial distribution accuracy, suggesting that the underlying structure of the model fails to capture one or more biological processes that affect tumor growth. Two biological features that are candidates for further investigation are angiogenesis and anisotropy resulting from differences between white and gray matter. Time-dependent proliferation and diffusion terms could be introduced to model angiogenesis, and diffusion weighed imaging (DTI) could be used to differentiate between white and gray matter, which might allow for improved estimates brain anisotropy.
ContributorsAnderies, Barrett James (Author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / Stepien, Tracy (Committee member) / Harrington Bioengineering Program (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Is it possible to treat the mouth as a natural environment, and determine new methods to keep the microbiome in check? The need for biodiversity in health may suggest that every species carries out a specific function that is required to maintain equilibrium and homeostasis within the oral cavity. Furthermore, the relationship between the microbiome and its host is mutually beneficial because the host is providing microbes with an environment in which they can flourish and, in turn, keep their host healthy. Reviewing examples of larger scale environmental shifts could provide a window by which scientists can make hypotheses. Certain medications and healthcare treatments have been proven to cause xerostomia. This disorder is characterized by a dry mouth, and known to be associated with a change in the composition, and reduction, of saliva. Two case studies performed by Bardow et al, and Leal et al, tested and studied the relationships of certain medications and confirmed their side effects on the salivary glands [2,3]. Their results confirmed a relationship between specific medicines, and the correlating complaints of xerostomia. In addition, Vissink et al conducted case studies that helped to further identify how radiotherapy causes hyposalivation of the salivary glands [4]. Specifically patients that have been diagnosed with oral cancer, and are treated by radiotherapy, have been diagnosed with xerostomia. As stated prior, studies have shown that patients having an ecologically balanced and diverse microbiome tend to have healthier mouths. The oral cavity is like any biome, consisting of commensalism within itself and mutualism with its host. Due to the decreased salivary output, caused by xerostomia, increased parasitic bacteria build up within the oral cavity thus causing dental disease. Every human body contains a personalized microbiome that is essential to maintaining health but capable of eliciting disease. The Human Oral Microbiomics Database (HOMD) is a set of reference 16S rRNA gene sequences. These are then used to define individual human oral taxa. By conducting metagenomic experiments at the molecular and cellular level, scientists can identify and label micro species that inhabit the mouth during parasitic outbreaks or a shifting of the microbiome. Because the HOMD is incomplete, so is our ability to cure, or prevent, oral disease. The purpose of the thesis is to research what is known about xerostomia and its effects on the complex microbiome of the oral cavity. It is important that researchers determine whether this particular perspective is worth considering. In addition, the goal is to create novel experiments for treatment and prevention of dental diseases.
ContributorsHalcomb, Michael Jordan (Author) / Chen, Qiang (Thesis director) / Steele, Kelly (Committee member) / Barrett, The Honors College (Contributor) / College of Letters and Sciences (Contributor)
Created2015-05
Description
Despite the 40-year war on cancer, very limited progress has been made in developing a cure for the disease. This failure has prompted the reevaluation of the causes and development of cancer. One resulting model, coined the atavistic model of cancer, posits that cancer is a default phenotype of the cells of multicellular organisms which arises when the cell is subjected to an unusual amount of stress. Since this default phenotype is similar across cell types and even organisms, it seems it must be an evolutionarily ancestral phenotype. We take a phylostratigraphical approach, but systematically add species divergence time data to estimate gene ages numerically and use these ages to investigate the ages of genes involved in cancer. We find that ancient disease-recessive cancer genes are significantly enriched for DNA repair and SOS activity, which seems to imply that a core component of cancer development is not the regulation of growth, but the regulation of mutation. Verification of this finding could drastically improve cancer treatment and prevention.
ContributorsOrr, Adam James (Author) / Davies, Paul (Thesis director) / Bussey, Kimberly (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Magnetic resonance imaging (MRI) data of metastatic brain cancer patients at the Barrow Neurological Institute sparked interest in the radiology department due to the possibility that tumor size distributions might mimic a power law or an exponential distribution. In order to consider the question regarding the growth trends of metastatic brain tumors, this thesis analyzes the volume measurements of the tumor sizes from the BNI data and attempts to explain such size distributions through mathematical models. More specifically, a basic stochastic cellular automaton model is used and has three-dimensional results that show similar size distributions of those of the BNI data. Results of the models are investigated using the likelihood ratio test suggesting that, when the tumor volumes are measured based on assuming tumor sphericity, the tumor size distributions significantly mimic the power law over an exponential distribution.
ContributorsFreed, Rebecca (Co-author) / Snopko, Morgan (Co-author) / Kostelich, Eric (Thesis director) / Kuang, Yang (Committee member) / WPC Graduate Programs (Contributor) / School of Accountancy (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Glioblastoma Multiforme (GBM) is an aggressive and deadly form of brain cancer with a median survival time of about a year with treatment. Due to the aggressive nature of these tumors and the tendency of gliomas to follow white matter tracks in the brain, each tumor mass has a unique growth pattern. Consequently it is difficult for neurosurgeons to anticipate where the tumor will spread in the brain, making treatment planning difficult. Archival patient data including MRI scans depicting the progress of tumors have been helpful in developing a model to predict Glioblastoma proliferation, but limited scans per patient make the tumor growth rate difficult to determine. Furthermore, patient treatment between scan points can significantly compound the challenge of accurately predicting the tumor growth. A partnership with Barrow Neurological Institute has allowed murine studies to be conducted in order to closely observe tumor growth and potentially improve the current model to more closely resemble intermittent stages of GBM growth without treatment effects.
ContributorsSnyder, Lena Haley (Author) / Kostelich, Eric (Thesis director) / Frakes, David (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Harrington Bioengineering Program (Contributor)
Created2014-05
Description
I, Christopher Negrich, am the sole author of this paper, but the tools described were designed in collaboration with Andrew Hoetker. ConstrictR (constrictor) and ConstrictPy are an R package and python tool designed together. ConstrictPy implements the functions and methods defined in ConstrictR and applies data handling, data parsing, input/output (I/O), and a user interface to increase usability. ConstrictR implements a variety of common data analysis methods used for statistical and subnetwork analysis. The majority of these methods are inspired by Lionel Guidi's 2016 paper, Plankton networks driving carbon export in the oligotrophic ocean. Additional methods were added to expand functionality, usability, and applicability to different areas of data science. Both ConstrictR and ConstrictPy are currently publicly available and usable, however, they are both ongoing projects. ConstrictR is available at github.com/cnegrich and ConstrictPy is available at github.com/ahoetker. Currently, ConstrictR has implemented functions for descriptive statistics, correlation, covariance, rank, sparsity, and weighted correlation network analysis with clustering, centrality, profiling, error handling, and data parsing methods to be released soon. ConstrictPy has fully implemented and integrated the features in ConstrictR as well as created functions for I/O and conversion between pandas and R data frames with a full feature user interface to be released soon. Both ConstrictR and ConstrictPy are designed to work with minimal dependencies and maximum available information on the algorithms implemented. As a result, ConstrictR is only dependent on base R (v3.4.4) functions with no libraries imported. ConstrictPy is dependent upon only pandas, Rpy2, and ConstrictR. This was done to increase longevity and independence of these tools. Additionally, all mathematical information is documented alongside the code, increasing the available information on how these tools function. Although neither tool is in its final version, this paper documents the code, mathematics, and instructions for use, in addition to plans for future work, for of the current versions of ConstrictR (v0.0.1) and ConstrictPy (v0.0.1).
ContributorsNegrich, Christopher Alec (Author) / Can, Huansheng (Thesis director) / Hansford, Dianne (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Speech nasality disorders are characterized by abnormal resonance in the nasal cavity. Hypernasal speech is of particular interest, characterized by an inability to prevent improper nasalization of vowels, and poor articulation of plosive and fricative consonants, and can lead to negative communicative and social consequences. It can be associated with a range of conditions, including cleft lip or palate, velopharyngeal dysfunction (a physical or neurological defective closure of the soft palate that regulates resonance between the oral and nasal cavity), dysarthria, or hearing impairment, and can also be an early indicator of developing neurological disorders such as ALS. Hypernasality is typically scored perceptually by a Speech Language Pathologist (SLP). Misdiagnosis could lead to inadequate treatment plans and poor treatment outcomes for a patient. Also, for some applications, particularly screening for early neurological disorders, the use of an SLP is not practical. Hence this work demonstrates a data-driven approach to objective assessment of hypernasality, through the use of Goodness of Pronunciation features. These features capture the overall precision of articulation of speaker on a phoneme-by-phoneme basis, allowing demonstrated models to achieve a Pearson correlation coefficient of 0.88 on low-nasality speakers, the population of most interest for this sort of technique. These results are comparable to milestone methods in this domain.
ContributorsSaxon, Michael Stephen (Author) / Berisha, Visar (Thesis director) / McDaniel, Troy (Committee member) / Electrical Engineering Program (Contributor, Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
In this paper, I will show that news headlines of global events can predict changes in stock price by using Machine Learning and eight years of data from r/WorldNews, a popular forum on Reddit.com. My data is confined to the top 25 daily posts on the forum, and due to the implicit filtering mechanism in the online community, these 25 posts are representative of the most popular news headlines and influential global events of the day. Hence, these posts shine a light on how large-scale social and political events affect the stock market. Using a Logistic Regression and a Naive Bayes classifier, I am able to predict with approximately 85% accuracy a binary change in stock price using term-feature vectors gathered from the news headlines. The accuracy, precision and recall results closely rival the best models in this field of research. In addition to the results, I will also describe the mathematical underpinnings of the two models; preceded by a general investigation of the intersection between the multiple academic disciplines related to this project. These range from social to computer science and from statistics to philosophy. The goal of this additional discussion is to further illustrate the interdisciplinary nature of the research and hopefully inspire a non-monolithic mindset when further investigations are pursued.
ContributorsPriniski, John Hunter (Author) / Haiyan, Wang (Thesis director) / Hazel, Kwon (Committee member) / School of Historical, Philosophical and Religious Studies (Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Over time, tumor treatment resistance inadvertently develops when androgen de-privation therapy (ADT) is applied to metastasized prostate cancer (PCa). To combat tumor resistance, while reducing the harsh side effects of hormone therapy, the clinician may opt to cyclically alternates the patient’s treatment on and off. This method,known as intermittent ADT, is an alternative to continuous ADT that improves the patient’s quality of life while testosterone levels recover between cycles. In this paper,we explore the response of intermittent ADT to metastasized prostate cancer by employing a previously clinical data validated mathematical model to new clinical data from patients undergoing Abiraterone therapy. This cell quota model, a system of ordinary differential equations constructed using Droop’s nutrient limiting theory, assumes the tumor comprises of castration-sensitive (CS) and castration-resistant (CR)cancer sub-populations. The two sub-populations rely on varying levels of intracellular androgen for growth, death and transformation. Due to the complexity of the model,we carry out sensitivity analyses to study the effect of certain parameters on their outputs, and to increase the identifiability of each patient’s unique parameter set. The model’s forecasting results show consistent accuracy for patients with sufficient data,which means the model could give useful information in practice, especially to decide whether an additional round of treatment would be effective.
ContributorsBennett, Justin Klark (Author) / Kuang, Yang (Thesis director) / Kostelich, Eric (Committee member) / Phan, Tin (Committee member) / School of Mathematical and Statistical Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Cancer rates vary between people, between cultures, and between tissue types, driven by clinically relevant distinctions in the risk factors that lead to different cancer types. Despite the importance of cancer location in human health, little is known about tissue-specific cancers in non-human animals. We can gain significant insight into how evolutionary history has shaped mechanisms of cancer suppression by examining how life history traits impact cancer susceptibility across species. Here, we perform multi-level analysis to test how species-level life history strategies are associated with differences in neoplasia prevalence, and apply this to mammary neoplasia within mammals. We propose that the same patterns of cancer prevalence that have been reported across species will be maintained at the tissue-specific level. We used a combination of factor analysis and phylogenetic regression on 13 life history traits across 90 mammalian species to determine the correlation between a life history trait and how it relates to mammary neoplasia prevalence. The factor analysis presented ways to calculate quantifiable underlying factors that contribute to covariance of entangled life history variables. A greater risk of mammary neoplasia was found to be correlated most significantly with shorter gestation length. With this analysis, a framework is provided for how different life history modalities can influence cancer vulnerability. Additionally, statistical methods developed for this project present a framework for future comparative oncology studies and have the potential for many diverse applications.
ContributorsFox, Morgan Shane (Author) / Maley, Carlo C. (Thesis director) / Boddy, Amy (Committee member) / Compton, Zachary (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05