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Browsing Department of Statistics by Department "Fralin Biomedical Research Institute"
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- Accurate human microsatellite genotypes from high-throughput resequencing data using informed error profilesHighnam, Gareth; Franck, Christopher T.; Martin, Andy; Stephens, Calvin; Puthige, Ashwin; Mittelman, David (Oxford University Press, 2013-01)Repetitive sequences are biologically and clinically important because they can influence traits and disease, but repeats are challenging to analyse using short-read sequencing technology. We present a tool for genotyping microsatellite repeats called RepeatSeq, which uses Bayesian model selection guided by an empirically derived error model that incorporates sequence and read properties. Next, we apply RepeatSeq to high-coverage genomes from the 1000 Genomes Project to evaluate performance and accuracy. The software uses common formats, such as VCF, for compatibility with existing genome analysis pipelines. Source code and binaries are available at http://github.com/adaptivegenome/repeatseq.
- Cell Cycle Model System for Advancing Cancer Biomarker ResearchLazar, Iuliana M.; Hoeschele, Ina; de Morais, Juliana; Tenga, Milagros J. (Springer Nature, 2017-12-21)Progress in understanding the complexity of a devastating disease such as cancer has underscored the need for developing comprehensive panels of molecular markers for early disease detection and precision medicine applications. The present study was conducted to assess whether a cohesive biological context can be assigned to protein markers derived from public data mining, and whether mass spectrometry can be utilized to screen for the co-expression of functionally related biomarkers to be recommended for further exploration in clinical context. Cell cycle arrest/release experiments of MCF7/SKBR3 breast cancer and MCF10 non-tumorigenic cells were used as a surrogate to support the production of proteins relevant to aberrant cell proliferation. Information downloaded from the scientific public domain was queried with bioinformatics tools to generate an initial list of 1038 cancer-associated proteins. Mass spectrometric analysis of cell extracts identified 352 proteins that could be matched to the public list. Differential expression, enrichment, and protein-protein interaction analysis of the proteomic data revealed several functionally-related clusters of relevance to cancer. The results demonstrate that public data derived from independent experiments can be used to inform biological research and support the development of molecular assays for probing the characteristics of a disease.
- Development and implementation of a scalable and versatile test for COVID-19 diagnostics in rural communitiesCeci, Alessandro; Muñoz-Ballester, Carmen; Tegge, Allison N.; Brown, Katherine L.; Umans, Robyn A.; Michel, F. Marc; Patel, Dipankumar; Tewari, Bhanu P.; Martin, James E.; Alcoreza, Oscar Jr.; Maynard, Thomas M.; Martinez-Martinez, Daniel; Bordwine, Paige; Bissell, Noelle; Friedlander, Michael J.; Sontheimer, Harald; Finkielstein, Carla V. (Nature Publishing Group, 2021-07-20)Rapid and widespread testing of severe acute respiratory coronavirus 2 (SARS-CoV-2) is essential for an effective public health response aimed at containing and mitigating the coronavirus disease 2019 (COVID-19) pandemic. Successful health policy implementation relies on early identification of infected individuals and extensive contact tracing. However, rural communities, where resources for testing are sparse or simply absent, face distinctive challenges to achieving this success. Accordingly, we report the development of an academic, public land grant University laboratory-based detection assay for the identification of SARS-CoV-2 in samples from various clinical specimens that can be readily deployed in areas where access to testing is limited. The test, which is a quantitative reverse transcription polymerase chain reaction (RT-qPCR)-based procedure, was validated on samples provided by the state laboratory and submitted for FDA Emergency Use Authorization. Our test exhibits comparable sensitivity and exceeds specificity and inclusivity values compared to other molecular assays. Additionally, this test can be re-configured to meet supply chain shortages, modified for scale up demands, and is amenable to several clinical specimens. Test development also involved 3D engineering critical supplies and formulating a stable collection media that allowed samples to be transported for hours over a dispersed rural region without the need for a cold-chain. These two elements that were critical when shortages impacted testing and when personnel needed to reach areas that were geographically isolated from the testing center. Overall, using a robust, easy-to-adapt methodology, we show that an academic laboratory can supplement COVID-19 testing needs and help local health departments assess and manage outbreaks. This additional testing capacity is particularly germane for smaller cities and rural regions that would otherwise be unable to meet the testing demand.
- Estimating the Impact of Tobacco Parity and Harm Reduction Tax Proposals Using the Experimental Tobacco MarketplaceFreitas Lemos, Roberta; Keith, Diana R.; Tegge, Allison N.; Stein, Jeffrey S.; Cummings, Kenneth Michael; Bickel, Warren K. (MDPI, 2021-07-23)Taxes are a demonstrably effective method to suppress tobacco use. This study examined the effects of the tobacco parity (i.e., imposing taxes equally on all tobacco products) and the harm reduction (i.e., applying taxes in proportion to the products’ levels of harm) tax proposals on demand and substitution across products. A crowdsourced sample of cigarette smokers (n = 35) completed purchasing trials with increasing tax magnitudes across different tax tiers in the Experimental Tobacco Marketplace in a repeated-measures design. Products were placed in three tax tiers (high, medium, and no tax) according to each proposal’s goal. The results indicated that total nicotine (mg) purchased was not significantly different between the proposals, with higher taxes yielding lower demand. However, as taxes increased, the tobacco parity proposal decreased the purchasing of all tobacco products and increased the purchasing of medicinal nicotine (i.e., the no tax tier). Conversely, the harm reduction proposal resulted in greater purchases of electronic nicotine delivery systems and smokeless tobacco (i.e., the medium tax tier). These findings support tobacco taxation as a robust tool for suppressing purchasing and suggest that differential taxation in proportion to product risk would be an effective way to incentivize smokers to switch from smoked to unsmoked products. Further studies should investigate the unintended consequences of their implementation.
- Medical Students' Knowledge and Perception of Deep Brain StimulationSaway, Brian F.; Monjazeb, Sanaz; Godbe, Kerilyn; Anwyll, Tessa; Kablinger, Anita S.; Witcher, Mark R. (2021-03)BACKGROUND: Deep brain stimulation (DBS) is a well-established neurosurgical procedure commonly used in movement and psychiatric disorders. Its widespread clinical implementation, however, may not be commensurate with medical education. No current assessment of medical student's understanding of DBS as a treatment option for indicated conditions is available, potentially threatening the availability of DBS to future patients. The aim of the present study is to explore the current knowledge and attitudes of medical students toward DBS as a treatment modality. METHODS: A total of 65 medical students at Virginia Tech Carilion School of Medicine were surveyed regarding their knowledge of DBS. The survey consisted of a 25-item questionnaire including a demographic section and 3 separate inventories designed to assess bias, knowledge, and self-assessment of knowledge specific to DBS therapy. Students in pre-clinical and clinical years were analyzed separately to describe changes in knowledge or attitude associated with clinical exposure to DBS. Comparisons were analyzed using t tests, ANOVA, and Pearson correlations. RESULTS: Of surveyed students, 36% were unsure of the FDA approval status of DBS treatment; 65% of students believed they had not been adequately educated about DBS and its utility; and 10.6% of students believed that DBS is likely associated with severe adverse effects and/or brain damage. The overall baseline attitudes of students toward DBS were positive. There was no observed difference between surveyed pre-clinical and clinical students, highlighting a lack of exposure throughout the clinical years of medical school education. CONCLUSION: Although DBS is an effective treatment modality for various conditions, current education is non-commensurate with its application, which can negatively impact awareness and understanding for its implications by medical professionals. In order to better serve patients who may benefit from DBS, medical curricula must change to educate future physicians on the benefit of this intervention.
- The phenotype of recovery IV: Delay discounting predicts perceived stress and a chance locus of control in individuals in recovery from substance use disordersTomlinson, Devin C.; Tegge, Allison N.; Athamneh, Liqa N.; Bickel, Warren K. (Elsevier, 2020-12-01)Objective: Understanding individuals who are successful in recovery from substance use disorders will help to inform treatments and preventative measures. Stress has been shown to be associated with both substance use and relapse. Delay discounting is associated with risk of substance use; it is predictive of treatment outcomes and maintained abstinence. Associations between perceived stress, beliefs about locus of control, and delay discounting have yet to be assessed in individuals in recovery from substance use disorder. Methods: Data from 93 individuals in recovery from substance use recruited from the International Quit and Recovery Registry (IQRR) were analyzed. Individuals completed the adjusting amount delay discounting procedure to obtain delay discounting rates. Level of perceived stress was assessed by the Perceived Stress Scale (PSS). An individual's belief about locus of control was assessed using the Internality, Powerful Others and Chance Scale (IPCS). Results: Delay discounting was a significant predictor of perceived stress and scores associated with beliefs about a Chance locus of control (i.e., belief that events that occur in an individual's life are because of chance or luck), even after controlling for demographic characteristics. Time in recovery was also predictive of levels of perceived stress; this relationship was mediated by delay discounting. Conclusion: The present study indicates that delay discounting can predict perception of stress and beliefs about a chance locus of control in individuals in recovery. This information may help understand, identify, and assist individuals whomay need different, new, or more intensive interventions for their substance use disorder.