Microarrays Commons^™

A Statistical Framework For The Analysis Of Chip-Seq Data, Pei Fen Kuan, Dongjun Chung, Guangjin Pan, James A. Thomson, Ron Stewart, Sunduz Keles

Sunduz Keles

Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) has revolutionalized experiments for genome-wide profiling of DNA-binding proteins, histone modifications, and nucleosome occupancy. As the cost of sequencing is decreasing, many researchers are switching from microarray-based technologies (ChIP-chip) to ChIP-Seq for genome-wide study of transcriptional regulation. Despite its increasing and well-deserved popularity, there is little work that investigates and accounts for sources of biases in the ChIP-Seq technology. These biases typically arise from both the standard pre-processing protocol and the underlying DNA sequence of the generated data.

We study data from a naked DNA sequencing experiment, which sequences non-cross-linked DNA after deproteinizing and …

Shrinkage Estimation Of Expression Fold Change As An Alternative To Testing Hypotheses Of Equivalent Expression, Zahra Montazeri, Corey M. Yanofsky, David R. Bickel

COBRA Preprint Series

Research on analyzing microarray data has focused on the problem of identifying differentially expressed genes to the neglect of the problem of how to integrate evidence that a gene is differentially expressed with information on the extent of its differential expression. Consequently, researchers currently prioritize genes for further study either on the basis of volcano plots or, more commonly, according to simple estimates of the fold change after filtering the genes with an arbitrary statistical significance threshold. While the subjective and informal nature of the former practice precludes quantification of its reliability, the latter practice is equivalent to using a …

The Effect Of Correlation In False Discovery Rate Estimation, Armin Schwartzman, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Multilevel Model To Address Batch Effects In Copy Number Estimation Using Snp Arrays, Robert B. Scharpf, Ingo Ruczinski, Benilton Carvalho, Betty Doan, Aravinda Chakravarti, Rafael A. Irizarry

Johns Hopkins University, Dept. of Biostatistics Working Papers

Submicroscopic changes in chromosomal DNA copy number dosage are common and have been implicated in many heritable diseases and cancers. Recent high-throughput technologies have a resolution that permits the detection of segmental changes in DNA copy number that span thousands of basepairs across the genome. Genome-wide association studies (GWAS) may simultaneously screen for copy number-phenotype and SNP-phenotype associations as part of the analytic strategy. However, genome-wide array analyses are particularly susceptible to batch effects as the logistics of preparing DNA and processing thousands of arrays often involves multiple laboratories and technicians, or changes over calendar time to the reagents and …

A Multilevel Model To Address Batch Effects In Copy Number Using Snp Arrays, Robert B. Scharpf, Ingo Ruczinski, Benilton Carvalho, Betty Doan, Aravinda Chakravarti, Rafael A. Irizarry

Johns Hopkins University, Dept. of Biostatistics Working Papers

Submicroscopic changes in chromosomal DNA copy number dosage are common and have been implicated in many heritable diseases and cancers. Recent high-throughput technologies have a resolution that permits the detection of segmental changes in DNA copy number that span thousands of basepairs across the genome. Genome-wide association studies (GWAS) may simultaneously screen for copy number-phenotype and SNP-phenotype associations as part of the analytic strategy. However, genome-wide array analyses are particularly susceptible to batch effects as the logistics of preparing DNA and processing thousands of arrays often involves multiple laboratories and technicians, or changes over calendar time to the reagents and …

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 …

Validation Of Differential Gene Expression Algorithms: Application Comparing Fold Change Estimation To Hypothesis Testing, David R. Bickel, Corey M. Yanofsky

COBRA Preprint Series

Sustained research on the problem of determining which genes are differentially expressed on the basis of microarray data has yielded a plethora of statistical algorithms, each justified by theory, simulation, or ad hoc validation and yet differing in practical results from equally justified algorithms. The widespread confusion on which method to use in practice has been exacerbated by the finding that simply ranking genes by their fold changes sometimes outperforms popular statistical tests.

Algorithms may be compared by quantifying each method's error in predicting expression ratios, whether such ratios are defined across microarray channels or between two independent groups. For …

Quantifying Uncertainty In Genotype Calls, Benilton Carvalho, Thomas A. Louis, Rafael A. Irizarry

Johns Hopkins University, Dept. of Biostatistics Working Papers

Genome-wide association studies (GWAS) are used to discover genes underlying complex, heritable disorders for which less powerful study designs have failed in the past. The number of GWAS has skyrocketed recently with findings reported in top journals and the mainstream media. Mircorarrays are the genotype calling technology of choice in GWAS as they permit exploration of more than a million single nucleotide polymorphisms (SNPs)simultaneously. The starting point for the statistical analyses used by GWAS, to determine association between loci and disease, are genotype calls (AA, AB, or BB). However, the raw data, microarray probe intensities, are heavily processed before arriving …

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.