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Full-Text Articles in Microarrays

Finding Cancer Subtypes In Microarray Data Using Random Projections, Debashis Ghosh Oct 2004

Finding Cancer Subtypes In Microarray Data Using Random Projections, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

One of the benefits of profiling of cancer samples using microarrays is the generation of molecular fingerprints that will define subtypes of disease. Such subgroups have typically been found in microarray data using hierarchical clustering. A major problem in interpretation of the output is determining the number of clusters. We approach the problem of determining disease subtypes using mixture models. A novel estimation procedure of the parameters in the mixture model is developed based on a combination of random projections and the expectation-maximization algorithm. Because the approach is probabilistic, our approach provides a measure for the number of true clusters …


Nonparametric Methods For Analyzing Replication Origins In Genomewide Data, Debashis Ghosh Jun 2004

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 Jun 2004

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 …


Covariate Adjustment In The Analysis Of Microarray Data From Clinical Studies, Debashis Ghosh, Arul Chinnaiyan Apr 2004

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 Feb 2004

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 …