Physical Sciences and Mathematics | Open Access Articles

2^K Factorials In Blocks Of Size 2, With Application To Two-Color Microarray Experiments, Kathleen F. Kerr

UW Biostatistics Working Paper Series

When a two-level design must be run in blocks of size two, there is a unique blocking scheme that enables estimation of all the main effects. Unfortunately this design does not enable estimation of any two-factor interactions. When the experimental goal is to estimate all main effects and two-factor interactions, it is necessary to combine replicates of the experiment that use different blocking schemes. In this paper we identify such designs for up to eight factors that enable estimation of all main effects and two-factor interactions with the fewest number of replications. In addition, we give a construction for general …

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Yeast Through The Ages: A Statistical Analysis Of Genetic Changes In Aging Yeast, Alison Wise '05, Johanna S. Hardin, Laura Hoopes

Pomona Faculty Publications and Research

Microarray technology allows for the expression levels of thousands of genes in a cell to be measured simultaneously. The technology provides great potential in the fields of biology and medicine, as the analysis of data obtained from microarray experiments gives insight into the roles of specific genes and the associated changes across experimental conditions (e.g., aging, mutation, radiation therapy, drug dosage). The application of statistical tools to microarray data can help make sense of the experiment and thereby advance genetic, biological, and medical research. Likewise, microarrays provide an exciting means through which to explore statistical techniques.

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Optimal Feature Selection For Nearest Centroid Classifiers, With Applications To Gene Expression Microarrays, Alan R. Dabney, John D. Storey

UW Biostatistics Working Paper Series

Nearest centroid classifiers have recently been successfully employed in high-dimensional applications. A necessary step when building a classifier for high-dimensional data is feature selection. Feature selection is typically carried out by computing univariate statistics for each feature individually, without consideration for how a subset of features performs as a whole. For subsets of a given size, we characterize the optimal choice of features, corresponding to those yielding the smallest misclassification rate. Furthermore, we propose an algorithm for estimating this optimal subset in practice. Finally, we investigate the applicability of shrinkage ideas to nearest centroid classifiers. We use gene-expression microarrays for …

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A Bayesian And Covariate Approach To Combine Results From Multiple Microarray Studies, John R. Stevens, R. W. Doerge

Conference on Applied Statistics in Agriculture

The growing popularity of microarray technology for testing changes in gene expression has resulted in multiple laboratories independently seeking to identify genes related to the same disease in the same organism. Despite the uniform nature of the technology, chance variation and fundamental differences between laboratories can result in considerable disagreement between the lists of significant candidate genes from each laboratory. By adjusting for known differences between laboratories through the use of covariates and employing a Bayesian framework to effectively account for between-laboratory variability, the results of multiple similar studies can be systematically combined via a meta-analysis. Meta-analyses yield additional information …

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A Platform-Independent Software Suite For Statistical Analysis Of High Dimensional Biology Data, David B. Allison, Jacob P. L. Brand, Jode W. Edwards, Gary L. Gadbury, Kyoungmi Kim, Tapan Mehta, Grier P. Page, Amit Patki, Vinodh Srinivasasainagendra, Prinal Trivedi, Jelai Wang, Stanislav O. Zakharkin

Mathematics and Statistics Faculty Research & Creative Works

Many efforts in microarray data analysis are focused on providing tools and methods for the qualitative analysis of microarray data. HDBStat! (High-Dimensional Biology-Statistics) is a software package designed for analysis of high dimensional biology data such as microarray data. It was initially developed for the analysis of microarray gene expression data, but it can also be used for some applications in proteomics and other aspects of genomics. HDBStat! provides statisticians and biologists a flexible and easy-to-use interface to analyze complex microarray data using a variety of methods for data preprocessing, quality control analysis and hypothesis testing.

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Multiple Testing Procedures: R Multtest Package And Applications To Genomics, Katherine S. Pollard, Sandrine Dudoit, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

The Bioconductor R package multtest implements widely applicable resampling-based single-step and stepwise multiple testing procedures (MTP) for controlling a broad class of Type I error rates, in testing problems involving general data generating distributions (with arbitrary dependence structures among variables), null hypotheses, and test statistics. The current version of multtest provides MTPs for tests concerning means, differences in means, and regression parameters in linear and Cox proportional hazards models. Procedures are provided to control Type I error rates defined as tail probabilities for arbitrary functions of the numbers of false positives and rejected hypotheses. These error rates include tail probabilities …

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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. …

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A Statistical Method For Constructing Transcriptional Regulatory Networks Using Gene Expression And Sequence Data , Biao Xing, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Transcriptional regulation is one of the most important means of gene regulation. Uncovering transcriptional regulatory network helps us to understand the complex cellular process. In this paper, we describe a comprehensive statistical approach for constructing the transcriptional regulatory network using data of gene expression, promoter sequence, and transcription factor binding sites. Our simulation studies show that the overall and false positive error rates in the estimated transcriptional regulatory network are expected to be small if the systematic noise in the constructed feature matrix is small. Our analysis based on 658 microarray experiments on yeast gene expression programs and 46 transcription …

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Evaluation Of Multiple Models To Distinguish Closely Related Forms Of Disease Using Dna Microarray Data: An Application To Multiple Myeloma, Johanna S. Hardin, Michael Waddell, C. David Page, Fenghuang Zhan, Bart Barlogie, John Shaughnessy, John J. Crowley

Pomona Faculty Publications and Research

Motivation: Standard laboratory classification of the plasma cell dyscrasia monoclonal gammopathy of undetermined significance (MGUS) and the overt plasma cell neoplasm multiple myeloma (MM) is quite accurate, yet, for the most part, biologically uninformative. Most, if not all, cancers are caused by inherited or acquired genetic mutations that manifest themselves in altered gene expression patterns in the clonally related cancer cells. Microarray technology allows for qualitative and quantitative measurements of the expression levels of thousands of genes simultaneously, and it has now been used both to classify cancers that are morphologically indistinguishable and to predict response to therapy. It is …

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Loss-Based Estimation With Cross-Validation: Applications To Microarray Data Analysis And Motif Finding, Sandrine Dudoit, Mark J. Van Der Laan, Sunduz Keles, Annette M. Molinaro, Sandra E. Sinisi, Siew Leng Teng

U.C. Berkeley Division of Biostatistics Working Paper Series

Current statistical inference problems in genomic data analysis involve parameter estimation for high-dimensional multivariate distributions, with typically unknown and intricate correlation patterns among variables. Addressing these inference questions satisfactorily requires: (i) an intensive and thorough search of the parameter space to generate good candidate estimators, (ii) an approach for selecting an optimal estimator among these candidates, and (iii) a method for reliably assessing the performance of the resulting estimator. We propose a unified loss-based methodology for estimator construction, selection, and performance assessment with cross-validation. In this approach, the parameter of interest is defined as the risk minimizer for a suitable …

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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.

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A Semiparametric Regression Model For Oligonucleotide Arrays, Jianhua Hu, Guosheng Yin

Journal of Modern Applied Statistical Methods

A semiparametric model incorporating the spline smoothing technique is proposed to study oligonucleotide gene expression data. No specific parametric functional form is assumed for mismatch probe intensities, which allows much more flexibility in the fitted model. The new approach improves the model fitting, hence the estimation of expression indexes. The method is applied to a data set of 18 HuGeneFL arrays.

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Multiple Hypothesis Testing In Microarray Experiments, Sandrine Dudoit, Juliet Popper Shaffer, Jennifer C. Boldrick

U.C. Berkeley Division of Biostatistics Working Paper Series

DNA microarrays are a new and promising biotechnology which allows the monitoring of expression levels in cells for thousands of genes simultaneously. An important and common question in microarray experiments is the identification of differentially expressed genes, i.e., genes whose expression levels are associated with a response or covariate of interest. The biological question of differential expression can be restated as a problem in multiple hypothesis testing: the simultaneous test for each gene of the null hypothesis of no association between the expression levels and the responses or covariates. As a typical microarray experiment measures expression levels for thousands of …

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Full-Text Articles in Physical Sciences and Mathematics

2^K Factorials In Blocks Of Size 2, With Application To Two-Color Microarray Experiments, Kathleen F. Kerr

UW Biostatistics Working Paper Series

Yeast Through The Ages: A Statistical Analysis Of Genetic Changes In Aging Yeast, Alison Wise '05, Johanna S. Hardin, Laura Hoopes

Pomona Faculty Publications and Research

Optimal Feature Selection For Nearest Centroid Classifiers, With Applications To Gene Expression Microarrays, Alan R. Dabney, John D. Storey

UW Biostatistics Working Paper Series

A Bayesian And Covariate Approach To Combine Results From Multiple Microarray Studies, John R. Stevens, R. W. Doerge

Conference on Applied Statistics in Agriculture

Mathematics and Statistics Faculty Research & Creative Works

Multiple Testing Procedures: R Multtest Package And Applications To Genomics, Katherine S. Pollard, Sandrine Dudoit, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

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

The University of Michigan Department of Biostatistics Working Paper Series

A Statistical Method For Constructing Transcriptional Regulatory Networks Using Gene Expression And Sequence Data , Biao Xing, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Evaluation Of Multiple Models To Distinguish Closely Related Forms Of Disease Using Dna Microarray Data: An Application To Multiple Myeloma, Johanna S. Hardin, Michael Waddell, C. David Page, Fenghuang Zhan, Bart Barlogie, John Shaughnessy, John J. Crowley

Pomona Faculty Publications and Research

Loss-Based Estimation With Cross-Validation: Applications To Microarray Data Analysis And Motif Finding, Sandrine Dudoit, Mark J. Van Der Laan, Sunduz Keles, Annette M. Molinaro, Sandra E. Sinisi, Siew Leng Teng

U.C. Berkeley Division of Biostatistics Working Paper Series

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

UW Biostatistics Working Paper Series

A Semiparametric Regression Model For Oligonucleotide Arrays, Jianhua Hu, Guosheng Yin

Journal of Modern Applied Statistical Methods

Multiple Hypothesis Testing In Microarray Experiments, Sandrine Dudoit, Juliet Popper Shaffer, Jennifer C. Boldrick

U.C. Berkeley Division of Biostatistics Working Paper Series