Wavelet-based noise reduction of cDNA microarray images

The advent of microarray imaging technology has lead to enormous progress in the life sciences by allowing scientists to analyze the expression of thousands of genes at a time. For complementary DNA (cDNA) microarray experiments, the raw data are a pair of red and green channel images corresponding to the treatment and control samples. These images are contaminated by a high level of noise due to the numerous noise sources affecting the image formation. A major challenge of microarray image analysis is the extraction of accurate gene expression measurements from the noisy microarray images. A crucial step in this process is denoising, which consists of reducing the noise in the observed microarray images while preserving the signal information as much as possible. This thesis deals with the problem of developing novel methods for reducing noise in cDNA microarray images for accurate estimation of the gene expression levels. Denoising methods based on the wavelet transform have shown significant success when applied to natural images. However, these methods are not very efficient for reducing noise in cDNA microarray images. An important reason for this is that existing methods are only capable of processing the red and green channel images separately. In doing so. they ignore the signal correlation as well as the noise correlation that exists between the wavelet coefficients of the two channels. The primary objective of this research is to design efficient wavelet-based noise reduction algorithms for cDNA microarray images that take into account these inter-channel dependencies by 'jointly' estimating the noise-free coefficients in both the channels. Denoising algorithms are developed using two types of wavelet transforms, namely, the frequently-used discrete wavelet transform (DWT) and the complex wavelet transform (CWT). The main advantage of using the DWT for denoising is that this transform is computationally very efficient. In order to obtain a better denoising performance for microarray images, however, the CWT is preferred to DWT because the former has good directional selectivity properties that are necessary for better representation of the circular edges of spots. The linear minimum mean squared error and maximum a posteriori estimation techniques are used to develop bivariate estimators for the noise-free coefficients of the two images. These estimators are derived by utilizing appropriate joint probability density functions for the image coefficients as well as the noise coefficients of the two channels. Extensive experimentations are carried out on a large set of cDNA microarray images to evaluate the performance of the proposed denoising methods as compared to the existing ones. Comparisons are made using standard metrics such as the peak signal-to-noise ratio (PSNR) for measuring the amount of noise removed from the pixels of the images, and the mean absolute error for measuring the accuracy of the estimated log-intensity ratios obtained from the denoised version of the images. Results indicate that the proposed denoising methods that are developed specifically for the microarray images do, indeed, lead to more accurate estimation of gene expression levels. Thus, it is expected that the proposed methods will play a significant role in improving the reliability of the results obtained from practical microarray experiments

Randomized Dimension Reduction on Massive Data

Scalability of statistical estimators is of increasing importance in modern applications and dimension reduction is often used to extract relevant information from data. A variety of popular dimension reduction approaches can be framed as symmetric generalized eigendecomposition problems. In this paper we outline how taking into account the low rank structure assumption implicit in these dimension reduction approaches provides both computational and statistical advantages. We adapt recent randomized low-rank approximation algorithms to provide efficient solutions to three dimension reduction methods: Principal Component Analysis (PCA), Sliced Inverse Regression (SIR), and Localized Sliced Inverse Regression (LSIR). A key observation in this paper is that randomization serves a dual role, improving both computational and statistical performance. This point is highlighted in our experiments on real and simulated data.Comment: 31 pages, 6 figures, Key Words:dimension reduction, generalized eigendecompositon, low-rank, supervised, inverse regression, random projections, randomized algorithms, Krylov subspace method

Improved processing of microarray data using image reconstruction techniques

Spotted cDNA microarray data analysis suffers from various problems such as noise from a variety of sources, missing data, inconsistency, and, of course, the presence of outliers. This paper introduces a new method that dramatically reduces the noise when processing the original image data. The proposed approach recreates the microarray slide image, as it would have been with all the genes removed. By subtracting this background recreation from the original, the gene ratios can be calculated with more precision and less influence from outliers and other artifacts that would normally make the analysis of this data more difficult. The new technique is also beneficial, as it does not rely on the accurate fitting of a region to each gene, with its only requirement being an approximate coordinate. In experiments conducted, the new method was tested against one of the mainstream methods of processing spotted microarray images. Our method is shown to produce much less variation in gene measurements. This evidence is supported by clustering results that show a marked improvement in accuracy

Challenges of Big Data Analysis

Big Data bring new opportunities to modern society and challenges to data scientists. On one hand, Big Data hold great promises for discovering subtle population patterns and heterogeneities that are not possible with small-scale data. On the other hand, the massive sample size and high dimensionality of Big Data introduce unique computational and statistical challenges, including scalability and storage bottleneck, noise accumulation, spurious correlation, incidental endogeneity, and measurement errors. These challenges are distinguished and require new computational and statistical paradigm. This article give overviews on the salient features of Big Data and how these features impact on paradigm change on statistical and computational methods as well as computing architectures. We also provide various new perspectives on the Big Data analysis and computation. In particular, we emphasis on the viability of the sparsest solution in high-confidence set and point out that exogeneous assumptions in most statistical methods for Big Data can not be validated due to incidental endogeneity. They can lead to wrong statistical inferences and consequently wrong scientific conclusions

Application of Volcano Plots in Analyses of mRNA Differential Expressions with Microarrays

Volcano plot displays unstandardized signal (e.g. log-fold-change) against noise-adjusted/standardized signal (e.g. t-statistic or -log10(p-value) from the t test). We review the basic and an interactive use of the volcano plot, and its crucial role in understanding the regularized t-statistic. The joint filtering gene selection criterion based on regularized statistics has a curved discriminant line in the volcano plot, as compared to the two perpendicular lines for the "double filtering" criterion. This review attempts to provide an unifying framework for discussions on alternative measures of differential expression, improved methods for estimating variance, and visual display of a microarray analysis result. We also discuss the possibility to apply volcano plots to other fields beyond microarray.Comment: 8 figure

Biophotonic Tools in Cell and Tissue Diagnostics.

In order to maintain the rapid advance of biophotonics in the U.S. and enhance our competitiveness worldwide, key measurement tools must be in place. As part of a wide-reaching effort to improve the U.S. technology base, the National Institute of Standards and Technology sponsored a workshop titled "Biophotonic tools for cell and tissue diagnostics." The workshop focused on diagnostic techniques involving the interaction between biological systems and photons. Through invited presentations by industry representatives and panel discussion, near- and far-term measurement needs were evaluated. As a result of this workshop, this document has been prepared on the measurement tools needed for biophotonic cell and tissue diagnostics. This will become a part of the larger measurement road-mapping effort to be presented to the Nation as an assessment of the U.S. Measurement System. The information will be used to highlight measurement needs to the community and to facilitate solutions