Browsing by Author "Guan, Ting"

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    Novel Statistical Methods for Multiple-variant Genetic Association Studies with Related Individuals
    Guan, Ting (Virginia Tech, 2018-07-09)
    Genetic association studies usually include related individuals. Meanwhile, high-throughput sequencing technologies produce data of multiple genetic variants. Due to linkage disequilibrium (LD) and familial relatedness, the genotype data from such studies often carries complex correlations. Moreover, missing values in genotype usually lead to loss of power in genetic association tests. Also, repeated measurements of phenotype and dynamic covariates from longitudinal studies bring in more opportunities but also challenges in the discovery of disease-related genetic factors. This dissertation focuses on developing novel statistical methods to address some challenging questions remaining in genetic association studies due to the aforementioned reasons. So far, a lot of methods have been proposed to detect disease-related genetic regions (e.g., genes, pathways). However, with multiple-variant data from a sample with relatedness, it is critical to account for the complex genotypic correlations when assessing genetic contribution. Recognizing the limitations of existing methods, in the first work of this dissertation, the Adaptive-weight Burden Test (ABT) --- a score test between a quantitative trait and the genotype data with complex correlations --- is proposed. ABT achieves higher power by adopting data-driven weights, which make good use of the LD and relatedness. Because the null distribution has been successfully derived, the computational simplicity of ABT makes it a good fit for genome-wide association studies. Genotype missingness commonly arises due to limitations in genotyping technologies. Imputation of the missing values in genotype usually improves quality of the data used in the subsequent association test and thus increases power. Complex correlations, though troublesome, provide the opportunity to proper handling of genotypic missingness. In the second part of this dissertation, a genotype imputation method is developed, which can impute the missingness in multiple genetic variants via the LD and the relatedness. The popularity of longitudinal studies in genetics and genomics calls for methods deliberately designed for repeated measurements. Therefore, a multiple-variant genetic association test for a longitudinal trait on samples with relatedness is developed, which treats the longitudinal measurements as observations of functions and thus takes into account the time factor properly.
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    Pit Latrine Fecal Sludge Resistance Using a Dynamic Cone Penetrometer in Low Income Areas in Mzuzu City, Malawi
    Chirwa, Charles F. C.; Hall, Ralph P.; Krometis, Leigh-Anne H.; Vance, Eric A.; Edwards, Adam; Guan, Ting; Holm, Rochelle H. (MDPI, 2017-02-03)
    Pit latrines can provide improved household sanitation, but without effective and inexpensive emptying options, they are often abandoned once full and may pose a public health threat. Emptying techniques can be difficult, as the sludge contents of each pit latrine are different. The design of effective emptying techniques (e.g., pumps) is limited by a lack of data characterizing typical in situ latrine sludge resistance. This investigation aimed to better understand the community education and technical engineering needs necessary to improve pit latrine management. In low income areas within Mzuzu city, Malawi, 300 pit latrines from three distinct areas were assessed using a dynamic cone penetrometer to quantify fecal sludge strength, and household members were surveyed to determine their knowledge of desludging procedures and practices likely to impact fecal sludge characteristics. The results demonstrate that there is a significant difference in sludge strength between lined and unlined pits within a defined area, though sludge hardened with depth, regardless of the pit type or region. There was only limited association between cone penetration depth and household survey data. To promote the adoption of pit emptying, it is recommended that households be provided with information that supports pit emptying, such as latrine construction designs, local pit emptying options, and cost. This study indicates that the use of a penetrometer test in the field prior to pit latrine emptying may facilitate the selection of appropriate pit emptying technology.
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    Survival kinase genes present prognostic significance in glioblastoma
    Varghese, Robin T.; Liang, Yanping; Guan, Ting; Franck, Christopher T.; Kelly, Deborah F.; Sheng, Zhi (Impact Journals, 2016-04-12)
    Cancer biomarkers with a strong predictive power for diagnosis/prognosis and a potential to be therapeutic targets have not yet been fully established. Here we employed a loss-of-function screen in glioblastoma (GBM), an infiltrative brain tumor with a dismal prognosis, and identified 20 survival kinase genes (SKGs). Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that the expression of CDCP1, CDKL5, CSNK1E, IRAK3, LATS2, PRKAA1, STK3, TBRG4, and ULK4 stratified GBM prognosis with or without temozolomide (TMZ) treatment as a covariate. For the first time, we found that GBM patients with a high level of NEK9 and PIK3CB had a greater chance of having recurrent tumors. The expression of CDCP1, IGF2R, IRAK3, LATS2, PIK3CB, ULK4, or VRK1 in primary GBM tumors was associated with recurrence-related prognosis. Notably, the level of PIK3CB in recurrent tumors was much higher than that in newly diagnosed ones. Congruent with these results, genes in the PI3K/AKT pathway showed a significantly strong correlation with recurrence rate, further highlighting the pivotal role of PIK3CB in the disease progression. Importantly, 17 SKGs together presented a novel GBM prognostic signature. SKGs identified herein are associated with recurrence rate and present prognostic significance in GBM, thereby becoming attractive therapeutic targets.