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Nonparametric variance estimation in the analysis of microarray data: a measurement error approach.

ABSTRACT: This article investigates the effects of measurement error on the estimation of nonparametric variance functions. We show that either ignoring measurement error or direct application of the simulation extrapolation, SIMEX, method leads to inconsistent estimators. Nevertheless, the direct SIMEX method can reduce bias relative to a naive estimator. We further propose a permutation SIMEX method which leads to consistent estimators in theory. The performance of both SIMEX methods depends on approximations to the exact extrapolants. Simulations show that both SIMEX methods perform better than ignoring measurement error. The methodology is illustrated using microarray data from colon cancer patients.

SUBMITTER: Carroll RJ

PROVIDER: S-EPMC2670068 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Nonparametric variance estimation in the analysis of microarray data: a measurement error approach.

Carroll Raymond J RJ Wang Yuedong Y

Biometrika 20080101 2

This article investigates the effects of measurement error on the estimation of nonparametric variance functions. We show that either ignoring measurement error or direct application of the simulation extrapolation, SIMEX, method leads to inconsistent estimators. Nevertheless, the direct SIMEX method can reduce bias relative to a naive estimator. We further propose a permutation SIMEX method which leads to consistent estimators in theory. The performance of both SIMEX methods depends on approxim ...[more]

PMID: 19381352

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Project description:BackgroundDNA microarrays open up a new horizon for studying the genetic determinants of disease. The high throughput nature of these arrays creates an enormous wealth of information, but also poses a challenge to data analysis. Inferential problems become even more pronounced as experimental designs used to collect data become more complex. An important example is multigroup data collected over different experimental groups, such as data collected from distinct stages of a disease process. We have developed a method specifically addressing these issues termed Bayesian ANOVA for microarrays (BAM). The BAM approach uses a special inferential regularization known as spike-and-slab shrinkage that provides an optimal balance between total false detections and total false non-detections. This translates into more reproducible differential calls. Spike and slab shrinkage is a form of regularization achieved by using information across all genes and groups simultaneously.ResultsBAMarray is a graphically oriented Java-based software package that implements the BAM method for detecting differentially expressing genes in multigroup microarray experiments (up to 256 experimental groups can be analyzed). Drop-down menus allow the user to easily select between different models and to choose various run options. BAMarraycan also be operated in a fully automated mode with preselected run options. Tuning parameters have been preset at theoretically optimal values freeing the user from such specifications. BAMarray provides estimates for gene differential effects and automatically estimates data adaptive, optimal cutoff values for classifying genes into biological patterns of differential activity across experimental groups. A graphical suite is a core feature of the product and includes diagnostic plots for assessing model assumptions and interactive plots that enable tracking of prespecified gene lists to study such things as biological pathway perturbations. The user can zoom in and lasso genes of interest that can then be saved for downstream analyses.ConclusionBAMarray is user friendly platform independent software that effectively and efficiently implements the BAM methodology. Classifying patterns of differential activity is greatly facilitated by a data adaptive cutoff rule and a graphical suite. BAMarray is licensed software freely available to academic institutions. More information can be found at http://www.bamarray.com.

Dataset Information

Nonparametric variance estimation in the analysis of microarray data: a measurement error approach.

Publications

Nonparametric variance estimation in the analysis of microarray data: a measurement error approach.

Similar Datasets

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