Microarrays Commons^™

Statistical Approaches Of Gene Set Analysis With Quantitative Trait Loci For High-Throughput Genomic Studies., Samarendra Das

Electronic Theses and Dissertations

Recently, gene set analysis has become the first choice for gaining insights into the underlying complex biology of diseases through high-throughput genomic studies, such as Microarrays, bulk RNA-Sequencing, single cell RNA-Sequencing, etc. It also reduces the complexity of statistical analysis and enhances the explanatory power of the obtained results. Further, the statistical structure and steps common to these approaches have not yet been comprehensively discussed, which limits their utility. Hence, a comprehensive overview of the available gene set analysis approaches used for different high-throughput genomic studies is provided. The analysis of gene sets is usually carried out based on …

Detecting Differentially Co-Expressed Gene Modules Via The Edge-Count Test, Anne Gratius Lin

Graduate Theses and Dissertations

Background

Gene expression profiling by microarray has been used to uncover molecular variations in many different diseases. Complementary to conventional differential expression analysis, differential co-expression analysis can identify gene markers from the systematic and granular level. There are three aspects for differential co-expression network analysis, including the network global topological comparison, differential co-expression cluster identification, and differential co-expressed genes and gene pair identification. To date, most of the methods available still rely on Pearson’s correlation coefficient despite its nonlinear insensitivity.

Results

Here we present an approach that is robust to nonlinearity by using the edge-count test for differential co-expression analysis. …

Feature Selection For Longitudinal Data By Using Sign Averages To Summarize Gene Expression Values Over Time, Suyan Tian, Chi Wang

Biostatistics Faculty Publications

With the rapid evolution of high-throughput technologies, time series/longitudinal high-throughput experiments have become possible and affordable. However, the development of statistical methods dealing with gene expression profiles across time points has not kept up with the explosion of such data. The feature selection process is of critical importance for longitudinal microarray data. In this study, we proposed aggregating a gene’s expression values across time into a single value using the sign average method, thereby degrading a longitudinal feature selection process into a classic one. Regularized logistic regression models with pseudogenes (i.e., the sign average of genes across time as predictors) …

Meta-Analysis Of Gene Expression Studies, Umaporn Siangphoe

Theses and Dissertations

Combining effect sizes from individual studies using random-effects models are commonly applied in high-dimensional gene expression data. However, unknown study heterogeneity can arise from inconsistency of sample qualities and experimental conditions. High heterogeneity of effect sizes can reduce statistical power of the models. We proposed two new methods for random effects estimation and measurements for model variation and strength of the study heterogeneity. We then developed a statistical technique to test for significance of random effects and identify heterogeneous genes. We also proposed another meta-analytic approach that incorporates informative weights in the random effects meta-analysis models. We compared the proposed …

Cluster Analysis Of Genomic Data With Applications In R, Katherine S. Pollard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In this paper, we provide an overview of existing partitioning and hierarchical clustering algorithms in R. We discuss statistical issues and methods in choosing the number of clusters, the choice of clustering algorithm, and the choice of dissimilarity matrix. In particular, we illustrate how the bootstrap can be employed as a statistical method in cluster analysis to establish the reproducibility of the clusters and the overall variability of the followed procedure. We also show how to visualize a clustering result by plotting ordered dissimilarity matrices in R. We present a new R package, hopach, which implements the hybrid clustering method, …

Nonparametric Methods For Analyzing Replication Origins In Genomewide Data, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

Due to the advent of high-throughput genomic technology, it has become possible to globally monitor cellular activities on a genomewide basis. With these new methods, scientists can begin to address important biological questions. One such question involves the identification of replication origins, which are regions in chromosomes where DNA replication is initiated. In addition, one hypothesis regarding replication origins is that their locations are non-random throughout the genome. In this article, we develop methods for identification of and cluster inference regarding replication origins involving genomewide expression data. We compare several nonparametric regression methods for the identification of replication origin locations. …

Semiparametric Methods For Identification Of Tumor Progression Genes From Microarray Data, Debashis Ghosh, Arul Chinnaiyan

The University of Michigan Department of Biostatistics Working Paper Series

The use of microarray data has become quite commonplace in medical and scientific experiments. We focus here on microarray data generated from cancer studies. It is potentially important for the discovery of biomarkers to identify genes whose expression levels correlate with tumor progression. In this article, we develop statistical procedures for the identification of such genes, which we term tumor progression genes. Two methods are considered in this paper. The first is use of a proportional odds procedure, combined with false discovery rate estimation techniques to adjust for the multiple testing problem. The second method is based on order-restricted estimation …

Classification Using Generalized Partial Least Squares, Beiying Ding, Robert Gentleman

Bioconductor Project Working Papers

The advances in computational biology have made simultaneous monitoring of thousands of features possible. The high throughput technologies not only bring about a much richer information context in which to study various aspects of gene functions but they also present challenge of analyzing data with large number of covariates and few samples. As an integral part of machine learning, classification of samples into two or more categories is almost always of interest to scientists. In this paper, we address the question of classification in this setting by extending partial least squares (PLS), a popular dimension reduction tool in chemometrics, in …

Covariate Adjustment In The Analysis Of Microarray Data From Clinical Studies, Debashis Ghosh, Arul Chinnaiyan

The University of Michigan Department of Biostatistics Working Paper Series

There is tremendous scientific interest in the analysis of gene expression data in clinical settings, such as oncology. In this paper, we describe the importance of adjusting for confounders and other prognostic factors in order to select for differentially expressed genes for followup validation studies. We develop two approaches to the analysis of microarray data in nonrandomized clinical settings. The first is an extension of the current significance analysis of microarray procedures, where other covariates are taken into account. The second is a novel covariate-adjusted regression modelling based on the receiver operating characteristic curve for the analysis of gene expression …

Mixture Models For Assessing Differential Expression In Complex Tissues Using Microarray Data, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

The use of DNA microarrays has become quite popular in many scientific and medical disciplines, such as in cancer research. One common goal of these studies is to determine which genes are differentially expressed between cancer and healthy tissue, or more generally, between two experimental conditions. A major complication in the molecular profiling of tumors using gene expression data is that the data represent a combination of tumor and normal cells. Much of the methodology developed for assessing differential expression with microarray data has assumed that tissue samples are homogeneous. In this article, we outline a general framework for determining …

Design Considerations For Efficient And Effective Microarray Studies, M. Kathleen Kerr

UW Biostatistics Working Paper Series

This paper describes the theoretical and practical issues in experimental design for gene expression microarrays. Specifically, this paper (1) discusses the basic principles of design (randomization, replication, and blocking) as they pertain to microarrays, and (2) provides some general guidelines for statisticians designing microarray studies.

A Method To Identify Significant Clusters In Gene Expression Data, Katherine S. Pollard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Clustering algorithms have been widely applied to gene expression data. For both hierarchical and partitioning clustering algorithms, selecting the number of significant clusters is an important problem and many methods have been proposed. Existing methods for selecting the number of clusters tend to find only the global patterns in the data (e.g.: the over and under expressed genes). We have noted the need for a better method in the gene expression context, where small, biologically meaningful clusters can be difficult to identify. In this paper, we define a new criteria, Mean Split Silhouette (MSS), which is a measure of cluster …

Identification Of Regulatory Elements Using A Feature Selection Method, Sunduz Keles, Mark J. Van Der Laan, Michael B. Eisen

U.C. Berkeley Division of Biostatistics Working Paper Series

Many methods have been described to identify regulatory motifs in the transcription control regions of genes that exhibit similar patterns of gene expression across a variety of experimental conditions. Here we focus on a single experimental condition, and utilize gene expression data to identify sequence motifs associated with genes that are activated under this experimental condition. We use a linear model with two way interactions to model gene expression as a function of sequence features (words) present in presumptive transcription control regions. The most relevant features are selected by a feature selection method called stepwise selection with monte carlo cross …

Statistical Inference For Simultaneous Clustering Of Gene Expression Data, Katherine S. Pollard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Current methods for analysis of gene expression data are mostly based on clustering and classification of either genes or samples. We offer support for the idea that more complex patterns can be identified in the data if genes and samples are considered simultaneously. We formalize the approach and propose a statistical framework for two-way clustering. A simultaneous clustering parameter is defined as a function of the true data generating distribution, and an estimate is obtained by applying this function to the empirical distribution. We illustrate that a wide range of clustering procedures, including generalized hierarchical methods, can be defined as …