Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- Genetics (10)
- Gene expression (5)
- Mixture models (3)
- Classification (2)
- Comparative genomic hybridization (2)
-
- Cross-validation (2)
- Density estimation (2)
- Differential expression (2)
- Microarray (2)
- Model selection (2)
- Multiple testing (2)
- Prediction (2)
- (Quasi)separation (1)
- Adjust p value (1)
- Aging (1)
- BLUPs; Kernel function; Model/variable selection; Nonparametric regression; Penalized likelihood; REML; Score test; Smoothing parameter; Support vector machines (1)
- Biological metadata (1)
- Bootstrap (1)
- Cancer genomics (1)
- Case-control study (1)
- Censored data (1)
- Changepoint (1)
- Clonality; array CGH; permutation test (1)
- Cluster analysis (1)
- Clustering (1)
- Crossing hazards (1)
- Crossover (1)
- Derivative estimation (1)
- Differential gene expression (1)
- Discrimination (1)
- Publication Year
Articles 1 - 26 of 26
Full-Text Articles in Microarrays
Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan
Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan
COBRA Preprint Series
One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards …
Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret
Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret
UW Biostatistics Working Paper Series
We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …
Minimum Description Length Measures Of Evidence For Enrichment, Zhenyu Yang, David R. Bickel
Minimum Description Length Measures Of Evidence For Enrichment, Zhenyu Yang, David R. Bickel
COBRA Preprint Series
In order to functionally interpret differentially expressed genes or other discovered features, researchers seek to detect enrichment in the form of overrepresentation of discovered features associated with a biological process. Most enrichment methods treat the p-value as the measure of evidence using a statistical test such as the binomial test, Fisher's exact test or the hypergeometric test. However, the p-value is not interpretable as a measure of evidence apart from adjustments in light of the sample size. As a measure of evidence supporting one hypothesis over the other, the Bayes factor (BF) overcomes this drawback of the p-value but lacks …
Sparse Linear Discriminant Analysis For Simultaneous Testing For The Significance Of A Gene Set/Pathway And Gene Selection, Michael C. Wu, Lingson Zhang, Zhaoxi Wang, David C. Christiani, Xihong Lin
Sparse Linear Discriminant Analysis For Simultaneous Testing For The Significance Of A Gene Set/Pathway And Gene Selection, Michael C. Wu, Lingson Zhang, Zhaoxi Wang, David C. Christiani, Xihong Lin
Harvard University Biostatistics Working Paper Series
No abstract provided.
Estimation And Testing For The Effect Of A Genetic Pathway On A Disease Outcome Using Logistic Kernel Machine Regression Via Logistic Mixed Models, Dawei Liu, Debashis Ghosh, Xihong Lin
Estimation And Testing For The Effect Of A Genetic Pathway On A Disease Outcome Using Logistic Kernel Machine Regression Via Logistic Mixed Models, Dawei Liu, Debashis Ghosh, Xihong Lin
Harvard University Biostatistics Working Paper Series
No abstract provided.
A Powerful And Flexible Multilocus Association Test For Quantitative Traits, Lydia Coulter Kwee, Dawei Liu, Xihong Lin, Debashis Ghosh, Michael P. Epstein
A Powerful And Flexible Multilocus Association Test For Quantitative Traits, Lydia Coulter Kwee, Dawei Liu, Xihong Lin, Debashis Ghosh, Michael P. Epstein
Harvard University Biostatistics Working Paper Series
No abstract provided.
Assessment Of A Cgh-Based Genetic Instability, David A. Engler, Yiping Shen, J F. Gusella, Rebecca A. Betensky
Assessment Of A Cgh-Based Genetic Instability, David A. Engler, Yiping Shen, J F. Gusella, Rebecca A. Betensky
Harvard University Biostatistics Working Paper Series
No abstract provided.
Survival Analysis With Large Dimensional Covariates: An Application In Microarray Studies, David A. Engler, Yi Li
Survival Analysis With Large Dimensional Covariates: An Application In Microarray Studies, David A. Engler, Yi Li
Harvard University Biostatistics Working Paper Series
Use of microarray technology often leads to high-dimensional and low- sample size data settings. Over the past several years, a variety of novel approaches have been proposed for variable selection in this context. However, only a small number of these have been adapted for time-to-event data where censoring is present. Among standard variable selection methods shown both to have good predictive accuracy and to be computationally efficient is the elastic net penalization approach. In this paper, adaptation of the elastic net approach is presented for variable selection both under the Cox proportional hazards model and under an accelerated failure time …
Statistical Evaluation Of Evidence For Clonal Allelic Alterations In Array-Cgh Experiments, Colin B. Begg, Kevin Eng, Adam Olshen, E S. Venkatraman
Statistical Evaluation Of Evidence For Clonal Allelic Alterations In Array-Cgh Experiments, Colin B. Begg, Kevin Eng, Adam Olshen, E S. Venkatraman
Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series
In recent years numerous investigators have conducted genetic studies of pairs of tumor specimens from the same patient to determine whether the tumors share a clonal origin. These studies have the potential to be of considerable clinical significance, especially in clinical settings where the distinction of a new primary cancer and metastatic spread of a previous cancer would lead to radically different indications for treatment. Studies of clonality have typically involved comparison of the patterns of somatic mutations in the tumors at candidate genetic loci to see if the patterns are sufficiently similar to indicate a clonal origin. More recently, …
Power Boosting In Genome-Wide Studies Via Methods For Multivariate Outcomes, Mary J. Emond
Power Boosting In Genome-Wide Studies Via Methods For Multivariate Outcomes, Mary J. Emond
UW Biostatistics Working Paper Series
Whole-genome studies are becoming a mainstay of biomedical research. Examples include expression array experiments, comparative genomic hybridization analyses and large case-control studies for detecting polymorphism/disease associations. The tactic of applying a regression model to every locus to obtain test statistics is useful in such studies. However, this approach ignores potential correlation structure in the data that could be used to gain power, particularly when a Bonferroni correction is applied to adjust for multiple testing. In this article, we propose using regression techniques for misspecified multivariate outcomes to increase statistical power over independence-based modeling at each locus. Even when the outcome …
Semiparametric Regression Of Multi-Dimensional Genetic Pathway Data: Least Squares Kernel Machines And Linear Mixed Models, Dawei Liu, Xihong Lin, Debashis Ghosh
Semiparametric Regression Of Multi-Dimensional Genetic Pathway Data: Least Squares Kernel Machines And Linear Mixed Models, Dawei Liu, Xihong Lin, Debashis Ghosh
Harvard University Biostatistics Working Paper Series
No abstract provided.
New Statistical Paradigms Leading To Web-Based Tools For Clinical/Translational Science, Knut M. Wittkowski
New Statistical Paradigms Leading To Web-Based Tools For Clinical/Translational Science, Knut M. Wittkowski
COBRA Preprint Series
As the field of functional genetics and genomics is beginning to mature, we become confronted with new challenges. The constant drop in price for sequencing and gene expression profiling as well as the increasing number of genetic and genomic variables that can be measured makes it feasible to address more complex questions. The success with rare diseases caused by single loci or genes has provided us with a proof-of-concept that new therapies can be developed based on functional genomics and genetics.
Common diseases, however, typically involve genetic epistasis, genomic pathways, and proteomic pattern. Moreover, to better understand the underlying biologi-cal …
The Clustering Of Regression Models Method With Applications In Gene Expression Data, Li-Xuan Qin, Steven G. Self
The Clustering Of Regression Models Method With Applications In Gene Expression Data, Li-Xuan Qin, Steven G. Self
UW Biostatistics Working Paper Series
Identification of differentially expressed genes and clustering of genes are two important and complementary objectives addressed with gene expression data. For the differential expression question, many "per-gene" analytic methods have been proposed. These methods can generally be characterized as using a regression function to independently model the observations for each gene; various adjustments for multiplicity are then used to interpret the statistical significance of these per-gene regression models over the collection of genes analyzed. Motivated by this common structure of per-gene models, we propose a new model-based clustering method -- the clustering of regression models method, which groups genes that …
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, …
Finding Cancer Subtypes In Microarray Data Using Random Projections, Debashis Ghosh
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 …
Significance Analysis Of Time Course Microarray Experiments, John D. Storey, Wenzhong Xiao, Jeffrey T. Leek, Ronald G. Tompkins, Ron W. Davis
Significance Analysis Of Time Course Microarray Experiments, John D. Storey, Wenzhong Xiao, Jeffrey T. Leek, Ronald G. Tompkins, Ron W. Davis
UW Biostatistics Working Paper Series
Characterizing the genome-wide dynamic regulation of gene expression is important and will be of much interest in the future. However, there is currently no established method for identifying differentially expressed genes in a time course study. Here we propose a significance method for analyzing time course microarray studies that can be applied to the typical types of comparisons and sampling schemes. This method is applied to two studies on humans. In one study, genes are identified that show differential expression over time in response to in vivo endotoxin administration. Using our method 7409 genes are called significant at a 1% …
Differential Expression With The Bioconductor Project, Anja Von Heydebreck, Wolfgang Huber, Robert Gentleman
Differential Expression With The Bioconductor Project, Anja Von Heydebreck, Wolfgang Huber, Robert Gentleman
Bioconductor Project Working Papers
A basic, yet challenging task in the analysis of microarray gene expression data is the identification of changes in gene expression that are associated with particular biological conditions. We discuss different approaches to this task and illustrate how they can be applied using software from the Bioconductor Project. A central problem is the high dimensionality of gene expression space, which prohibits a comprehensive statistical analysis without focusing on particular aspects of the joint distribution of the genes expression levels. Possible strategies are to do univariate gene-by-gene analysis, and to perform data-driven nonspecific filtering of genes before the actual statistical analysis. …
Nonparametric Methods For Analyzing Replication Origins In Genomewide Data, Debashis Ghosh
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
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
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 …
Optimal Sample Size For Multiple Testing: The Case Of Gene Expression Microarrays, Peter Muller, Giovanni Parmigiani, Christian Robert, Judith Rousseau
Optimal Sample Size For Multiple Testing: The Case Of Gene Expression Microarrays, Peter Muller, Giovanni Parmigiani, Christian Robert, Judith Rousseau
Johns Hopkins University, Dept. of Biostatistics Working Papers
We consider the choice of an optimal sample size for multiple comparison problems. The motivating application is the choice of the number of microarray experiments to be carried out when learning about differential gene expression. However, the approach is valid in any application that involves multiple comparisons in a large number of hypothesis tests. We discuss two decision problems in the context of this setup: the sample size selection and the decision about the multiple comparisons. We adopt a decision theoretic approach,using loss functions that combine the competing goals of discovering as many ifferentially expressed genes as possible, while keeping …
Calibrating Observed Differential Gene Expression For The Multiplicity Of Genes On The Array, Yingye Zheng, Margaret S. Pepe
Calibrating Observed Differential Gene Expression For The Multiplicity Of Genes On The Array, Yingye Zheng, Margaret S. Pepe
UW Biostatistics Working Paper Series
In a gene expression array study, the expression levels of thousands of genes are monitored simultaneously across various biological conditions on a small set of subjects. One goal of such studies is to explore a large pool of genes in order to select a subset of genes that appear to be differently expressed for further investigation. Of particular interest here is how to select the top k genes once genes are ranked based on their evidence for differential expression in two tissue types. We consider statistical methods that provide a more rigorous and intuitively appealing selection process for k. We …
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 …
Selecting Differentially Expressed Genes From Microarray Experiments, Margaret S. Pepe, Gary M. Longton, Garnet L. Anderson, Michel Schummer
Selecting Differentially Expressed Genes From Microarray Experiments, Margaret S. Pepe, Gary M. Longton, Garnet L. Anderson, Michel Schummer
UW Biostatistics Working Paper Series
High throughput technologies, such as gene expression arrays and protein mass spectrometry, allow one to simultaneously evaluate thousands of potential biomarkers that distinguish different tissue types. Of particular interest here is cancer versus normal organ tissues. We consider statistical methods to rank genes (or proteins) in regards to differential expression between tissues. Various statistical measures are considered and we argue that two measures related to the Receiver Operating Characteristic Curve are particularly suitable for this purpose. We also propose that sampling variability in the gene rankings be quantified and suggest using the “selection probability function”, the probability distribution of rankings …
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, …
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 …