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Articles 1 - 12 of 12
Full-Text Articles in Microarrays
Super Learner In Prediction, Eric C. Polley, Mark J. Van Der Laan
Super Learner In Prediction, Eric C. Polley, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
Super learning is a general loss based learning method that has been proposed and analyzed theoretically in van der Laan et al. (2007). In this article we consider super learning for prediction. The super learner is a prediction method designed to find the optimal combination of a collection of prediction algorithms. The super learner algorithm finds the combination of algorithms minimizing the cross-validated risk. The super learner framework is built on the theory of cross-validation and allows for a general class of prediction algorithms to be considered for the ensemble. Due to the previously established oracle results for the cross-validation …
Resampling-Based Multiple Hypothesis Testing With Applications To Genomics: New Developments In The R/Bioconductor Package Multtest, Houston N. Gilbert, Katherine S. Pollard, Mark J. Van Der Laan, Sandrine Dudoit
Resampling-Based Multiple Hypothesis Testing With Applications To Genomics: New Developments In The R/Bioconductor Package Multtest, Houston N. Gilbert, Katherine S. Pollard, Mark J. Van Der Laan, Sandrine Dudoit
U.C. Berkeley Division of Biostatistics Working Paper Series
The multtest package is a standard Bioconductor package containing a suite of functions useful for executing, summarizing, and displaying the results from a wide variety of multiple testing procedures (MTPs). In addition to many popular MTPs, the central methodological focus of the multtest package is the implementation of powerful joint multiple testing procedures. Joint MTPs are able to account for the dependencies between test statistics by effectively making use of (estimates of) the test statistics joint null distribution. To this end, two additional bootstrap-based estimates of the test statistics joint null distribution have been developed for use in the …
Targeted Methods For Biomarker Discovery, The Search For A Standard, Catherine Tuglus, Mark J. Van Der Laan
Targeted Methods For Biomarker Discovery, The Search For A Standard, Catherine Tuglus, Mark J. Van Der Laan
U.C. Berkeley Division of Biostatistics Working Paper Series
More often than not biomarker studies analyze large quantities of variables with complicated and generally unknown correlation structure. There are numerous statistical methods which attempt to unravel these variables and determine the underlying mechanism through identification of causally related biomarkers. Results from these methods are generally difficult to interpret and nearly impossible to compare across studies. The FDA has currently called for a standardization of methods and protocol for biomarker detection. In response, we propose targeted variable importance (tVIM) as a standardized method for biomarker discovery. Through the use of targeted Maximum Likelihood, tVIM provides double robust estimates of variable …
Cluster Analysis Of Genomic Data With Applications In R, Katherine S. Pollard, Mark J. Van Der Laan
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, …
Regulatory Motif Finding By Logic Regression, Sunduz Keles, Mark J. Van Der Laan, Chris Vulpe
Regulatory Motif Finding By Logic Regression, Sunduz Keles, Mark J. Van Der Laan, Chris Vulpe
U.C. Berkeley Division of Biostatistics Working Paper Series
Multiple transcription factors coordinately control transcriptional regulation of genes in eukaryotes. Although multiple computational methods consider the identification of individual transcription factor binding sites (TFBSs), very few focus on the interactions between these sites. We consider finding transcription factor binding sites and their context specific interactions using microarray gene expression data. We devise a hybrid approach called LogicMotif composed of a TFBS identification method combined with the new regression methodology logic regression of Ruczinski et al. (2003). LogicMotif has two steps: First potential binding sites are identified from transcription control regions of genes of interest. Various available methods can be …
A Statistical Method For Constructing Transcriptional Regulatory Networks Using Gene Expression And Sequence Data , Biao Xing, Mark J. Van Der Laan
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 …
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
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 …
Multiple Hypothesis Testing In Microarray Experiments, Sandrine Dudoit, Juliet Popper Shaffer, Jennifer C. Boldrick
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 …
Comparative Genomic Hybridization Array Analysis, Annette M. Molinaro, Mark J. Van Der Laan, Dan H. Moore
Comparative Genomic Hybridization Array Analysis, Annette M. Molinaro, Mark J. Van Der Laan, Dan H. Moore
U.C. Berkeley Division of Biostatistics Working Paper Series
At the present time, there is increasing evidence that cancer may be regulated by the number of copies of genes in tumor cells. Through microarray technology it is now possible to measure the number of copies of thousands of genes and gene segments in samples of chromosomal DNA. Microarray comparative genomic hybridization (array CGH) provides the opportunity to both measure DNA sequence copy number gains and losses and map these aberrations to the genomic sequence. Gains can signify the over-expression of oncogenes, genes which stimulate cell growth and have become hyperactive, while losses can signify under-expression of tumor suppressor genes, …
A Method To Identify Significant Clusters In Gene Expression Data, Katherine S. Pollard, Mark J. Van Der Laan
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
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
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 …