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. ^

The nature of microvariability in blazar 0716+714

We organized an international campaign to observe the blazar 0716+714 in the optical band. The observations took place from February 24, 2009 to February 26, 2009. The global campaign was carried out by observers from more that sixteen countries and resulted in an extended light curve nearly seventy-eight hours long. The analysis and the modeling of this light curve form the main work of this dissertation project. In the first part of this work, we present the time series and noise analyses of the data. The time series analysis utilizes discrete Fourier transform and wavelet analysis routines to search for periods in the light curve. We then present results of the noise analysis which is based on the idea that each microvariability curve is the realization of the same underlying stochastic noise processes in the blazar jet. ^ Neither reoccuring periods nor random noise can successfully explain the observed optical fluctuations. Hence in the second part, we propose and develop a new model to account for the microvariability we see in blazar 0716+714. We propose that the microvariability is due to the emission from turbulent regions in the jet that are energized by the passage of relativistic shocks. Emission from each turbulent cell forms a pulse of emission, and when convolved with other pulses, yields the observed light curve. We use the model to obtain estimates of the physical parameters of the emission regions in the jet.^

The Nature of Microvariability in Blazar 0716+714

We organized an international campaign to observe the blazar 0716+714 in the optical band. The observations took place from February 24, 2009 to February 26, 2009. The global campaign was carried out by observers from more that sixteen countries and resulted in an extended light curve nearly seventy-eight hours long. The analysis and the modeling of this light curve form the main work of this dissertation project. In the first part of this work, we present the time series and noise analyses of the data. The time series analysis utilizes discrete Fourier transform and wavelet analysis routines to search for periods in the light curve. We then present results of the noise analysis which is based on the idea that each microvariability curve is the realization of the same underlying stochastic noise processes in the blazar jet. Neither reoccuring periods nor random noise can successfully explain the observed optical fluctuations. Hence in the second part, we propose and develop a new model to account for the microvariability we see in blazar 0716+714. We propose that the microvariability is due to the emission from turbulent regions in the jet that are energized by the passage of relativistic shocks. Emission from each turbulent cell forms a pulse of emission, and when convolved with other pulses, yields the observed light curve. We use the model to obtain estimates of the physical parameters of the emission regions in the jet.