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. ^

On-screen pre-deblurring of digital images using the wavefront aberration function of the human eye to improve computer access for the visually impaired

Traditional Optics has provided ways to compensate some common visual limitations (up to second order visual impairments) through spectacles or contact lenses. Recent developments in wavefront science make it possible to obtain an accurate model of the Point Spread Function (PSF) of the human eye. Through what is known as the "Wavefront Aberration Function" of the human eye, exact knowledge of the optical aberration of the human eye is possible, allowing a mathematical model of the PSF to be obtained. This model could be used to pre-compensate (inverse-filter) the images displayed on computer screens in order to counter the distortion in the user's eye. This project takes advantage of the fact that the wavefront aberration function, commonly expressed as a Zernike polynomial, can be generated from the ophthalmic prescription used to fit spectacles to a person. This allows the pre-compensation, or onscreen deblurring, to be done for various visual impairments, up to second order (commonly known as myopia, hyperopia, or astigmatism). The technique proposed towards that goal and results obtained using a lens, for which the PSF is known, that is introduced into the visual path of subjects without visual impairment will be presented. In addition to substituting the effect of spectacles or contact lenses in correcting the loworder visual limitations of the viewer, the significance of this approach is that it has the potential to address higher-order abnormalities in the eye, currently not correctable by simple means.

Motion correction algorithm of lung tumors for respiratory gated PET images

Respiratory gating in lung PET imaging to compensate for respiratory motion artifacts is a current research issue with broad potential impact on quantitation, diagnosis and clinical management of lung tumors. However, PET images collected at discrete bins can be significantly affected by noise as there are lower activity counts in each gated bin unless the total PET acquisition time is prolonged, so that gating methods should be combined with imaging-based motion correction and registration methods. The aim of this study was to develop and validate a fast and practical solution to the problem of respiratory motion for the detection and accurate quantitation of lung tumors in PET images. This included: (1) developing a computer-assisted algorithm for PET/CT images that automatically segments lung regions in CT images, identifies and localizes lung tumors of PET images; (2) developing and comparing different registration algorithms which processes all the information within the entire respiratory cycle and integrate all the tumor in different gated bins into a single reference bin. Four registration/integration algorithms: Centroid Based, Intensity Based, Rigid Body and Optical Flow registration were compared as well as two registration schemes: Direct Scheme and Successive Scheme. Validation was demonstrated by conducting experiments with the computerized 4D NCAT phantom and with a dynamic lung-chest phantom imaged using a GE PET/CT System. Iterations were conducted on different size simulated tumors and different noise levels. Static tumors without respiratory motion were used as gold standard; quantitative results were compared with respect to tumor activity concentration, cross-correlation coefficient, relative noise level and computation time. Comparing the results of the tumors before and after correction, the tumor activity values and tumor volumes were closer to the static tumors (gold standard). Higher correlation values and lower noise were also achieved after applying the correction algorithms. With this method the compromise between short PET scan time and reduced image noise can be achieved, while quantification and clinical analysis become fast and precise.

Motion Correction Algorithm of Lung Tumors for Respiratory Gated PET Images

Respiratory gating in lung PET imaging to compensate for respiratory motion artifacts is a current research issue with broad potential impact on quantitation, diagnosis and clinical management of lung tumors. However, PET images collected at discrete bins can be significantly affected by noise as there are lower activity counts in each gated bin unless the total PET acquisition time is prolonged, so that gating methods should be combined with imaging-based motion correction and registration methods. The aim of this study was to develop and validate a fast and practical solution to the problem of respiratory motion for the detection and accurate quantitation of lung tumors in PET images. This included: (1) developing a computer-assisted algorithm for PET/CT images that automatically segments lung regions in CT images, identifies and localizes lung tumors of PET images; (2) developing and comparing different registration algorithms which processes all the information within the entire respiratory cycle and integrate all the tumor in different gated bins into a single reference bin. Four registration/integration algorithms: Centroid Based, Intensity Based, Rigid Body and Optical Flow registration were compared as well as two registration schemes: Direct Scheme and Successive Scheme. Validation was demonstrated by conducting experiments with the computerized 4D NCAT phantom and with a dynamic lung-chest phantom imaged using a GE PET/CT System. Iterations were conducted on different size simulated tumors and different noise levels. Static tumors without respiratory motion were used as gold standard; quantitative results were compared with respect to tumor activity concentration, cross-correlation coefficient, relative noise level and computation time. Comparing the results of the tumors before and after correction, the tumor activity values and tumor volumes were closer to the static tumors (gold standard). Higher correlation values and lower noise were also achieved after applying the correction algorithms. With this method the compromise between short PET scan time and reduced image noise can be achieved, while quantification and clinical analysis become fast and precise.