Statistical analysis and meta-analysis of microarray data

The microarray technology provides a high-throughput technique to study gene expression. Microarrays can help us diagnose different types of cancers, understand biological processes, assess host responses to drugs and pathogens, find markers for specific diseases, and much more. Microarray experiments generate large amounts of data. Thus, effective data processing and analysis are critical for making reliable inferences from the data. ^ The first part of dissertation addresses the problem of finding an optimal set of genes (biomarkers) to classify a set of samples as diseased or normal. Three statistical gene selection methods (GS, GS-NR, and GS-PCA) were developed to identify a set of genes that best differentiate between samples. A comparative study on different classification tools was performed and the best combinations of gene selection and classifiers for multi-class cancer classification were identified. For most of the benchmarking cancer data sets, the gene selection method proposed in this dissertation, GS, outperformed other gene selection methods. The classifiers based on Random Forests, neural network ensembles, and K-nearest neighbor (KNN) showed consistently god performance. A striking commonality among these classifiers is that they all use a committee-based approach, suggesting that ensemble classification methods are superior. ^ The same biological problem may be studied at different research labs and/or performed using different lab protocols or samples. In such situations, it is important to combine results from these efforts. The second part of the dissertation addresses the problem of pooling the results from different independent experiments to obtain improved results. Four statistical pooling techniques (Fisher inverse chi-square method, Logit method. Stouffer's Z transform method, and Liptak-Stouffer weighted Z-method) were investigated in this dissertation. These pooling techniques were applied to the problem of identifying cell cycle-regulated genes in two different yeast species. As a result, improved sets of cell cycle-regulated genes were identified. The last part of dissertation explores the effectiveness of wavelet data transforms for the task of clustering. Discrete wavelet transforms, with an appropriate choice of wavelet bases, were shown to be effective in producing clusters that were biologically more meaningful. ^

Quantitative Comparison of Plant Community Hydrology Using Large-Extent, Long-Term Data

Large-extent vegetation datasets that co-occur with long-term hydrology data provide new ways to develop biologically meaningful hydrologic variables and to determine plant community responses to hydrology. We analyzed the suitability of different hydrological variables to predict vegetation in two water conservation areas (WCAs) in the Florida Everglades, USA, and developed metrics to define realized hydrologic optima and tolerances. Using vegetation data spatially co-located with long-term hydrological records, we evaluated seven variables describing water depth, hydroperiod length, and number of wet/dry events; each variable was tested for 2-, 4- and 10-year intervals for Julian annual averages and environmentally-defined hydrologic intervals. Maximum length and maximum water depth during the wet period calculated for environmentally-defined hydrologic intervals over a 4-year period were the best predictors of vegetation type. Proportional abundance of vegetation types along hydrological gradients indicated that communities had different realized optima and tolerances across WCAs. Although in both WCAs, the trees/shrubs class was on the drier/shallower end of hydrological gradients, while slough communities occupied the wetter/deeper end, the distribution ofCladium, Typha, wet prairie and Salix communities, which were intermediate for most hydrological variables, varied in proportional abundance along hydrologic gradients between WCAs, indicating that realized optima and tolerances are context-dependent.

Improved Criteria for Estimating Calibration Factors for Highway Safety Manual (HSM) Applications

The Highway Safety Manual (HSM) estimates roadway safety performance based on predictive models that were calibrated using national data. Calibration factors are then used to adjust these predictive models to local conditions for local applications. The HSM recommends that local calibration factors be estimated using 30 to 50 randomly selected sites that experienced at least a total of 100 crashes per year. It also recommends that the factors be updated every two to three years, preferably on an annual basis. However, these recommendations are primarily based on expert opinions rather than data-driven research findings. Furthermore, most agencies do not have data for many of the input variables recommended in the HSM. This dissertation is aimed at determining the best way to meet three major data needs affecting the estimation of calibration factors: (1) the required minimum sample sizes for different roadway facilities, (2) the required frequency for calibration factor updates, and (3) the influential variables affecting calibration factors. In this dissertation, statewide segment and intersection data were first collected for most of the HSM recommended calibration variables using a Google Maps application. In addition, eight years (2005-2012) of traffic and crash data were retrieved from existing databases from the Florida Department of Transportation. With these data, the effect of sample size criterion on calibration factor estimates was first studied using a sensitivity analysis. The results showed that the minimum sample sizes not only vary across different roadway facilities, but they are also significantly higher than those recommended in the HSM. In addition, results from paired sample t-tests showed that calibration factors in Florida need to be updated annually. To identify influential variables affecting the calibration factors for roadway segments, the variables were prioritized by combining the results from three different methods: negative binomial regression, random forests, and boosted regression trees. Only a few variables were found to explain most of the variation in the crash data. Traffic volume was consistently found to be the most influential. In addition, roadside object density, major and minor commercial driveway densities, and minor residential driveway density were also identified as influential variables.