Multiple Hypothesis Testing in Microarray Experiments

Dudoit, Sandrine; Shaffer, Juliet Popper; Boldrick, Jennifer C.

doi:10.1214/ss/1056397487

Cited by 897 publications

(679 citation statements)

References 50 publications

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“…The p values were used to identify genes with significant hybridization signals, and were adjusted by the BenjaminiHochberg method to control the per-chip false discovery rate (FDR), using the ''mt.rawp2adjp'' procedure in Bioconductor [45]. Only genes with an FDR-adjusted p value not exceeding 0.01 were selected.…”

Section: Statistical Analysesmentioning

confidence: 99%

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Wyrobek

Manohar

Krishnan

et al. 2011

Mutation Research/Genetic Toxicology and Environmental Mutagene

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We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues.Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of ~80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.

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Section: Statistical Analysesmentioning

confidence: 99%

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Wyrobek

Manohar

Krishnan

et al. 2011

Mutation Research/Genetic Toxicology and Environmental Mutagene

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show abstract

“…There are many statistical papers on controlling different aspects of false discovery rate. Storey et al (15) and Dudoit et al (17) provided an overview of these statistical methods in genomic applications. These techniques require Ps to be estimated very accurately, usually in the order of 10 À6 .…”

Section: Selecting Significant Genesmentioning

confidence: 99%

Statistical Analysis of DNA Microarray Data in Cancer Research

Fan

Ren²

2006

Clinical Cancer Research

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Microarray techniques have been widely used to monitor gene expression in many areas of biomedical research. They have been widely used for tumor diagnosis and classification, prediction of prognoses and treatment, and understanding of molecular mechanisms, biochemical pathways, and gene networks. Statistical methods are vital for these scientific endeavors. This article reviews recent developments of statistical methods for analyzing data from microarray experiments. Emphasis has been given to normalization of expression from multiple arrays, selecting significantly differentially expressed genes, tumor classifications, and gene expression pathways and networks.

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“…P Value and FDRs. The P value was computed by using the permutation test (30,31). To reduce possible biases in the permutation, only genes with P values, computed under the t distribution with degree of freedom m ϩ n Ϫ 2, of Ͼ5% were considered.…”

Section: Mif Expression In Cells Transfected With Mif Antisense Exprementioning

confidence: 99%

Removing intensity effects and identifying significant genes for Affymetrix arrays in macrophage migration inhibitory factor-suppressed neuroblastoma cells

Fan

Chen

Chan

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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A semilinear in-slide model is introduced to remove the intensity effect in the scanning process. It is demonstrated that the intensity effect can be estimated accurately and removed effectively. This normalization step is vital for Affymetrix arrays to reveal relevant biological results when comparing gene expression in multiple arrays. The normalized expression ratios are analyzed further by a modified two-sample t test along with a sieved permutation scheme for computing P values. The improved specificity and sensitivity are demonstrated by using a study on the impact of macrophage migration inhibitory factor (MIF) reduction in neuroblastoma cells. With semilinear in-slide model analysis, expression of 166 genes was altered with a P value no greater than 0.001. Among those genes, 44 were altered >2-fold. MIF-regulated genes associated with tumor development including IL-8 and C-met, which are overexpressed in many tumors, were down-regulated in MIF-reduced cells. On the other hand, some tumor-suppressor genes such as EPHB6, visinin-like protein 1 (VSNL-1), and BLU were up-regulated in MIF-reduced cells. In addition, we demonstrated that down-regulation of MIF expression could result in a reduction in cell proliferation and tumor growth in vitro and in vivo. Our data not only demonstrate that targeting MIF expression is a promising therapeutic strategy in human neuroblastoma therapy but also indicate the MIF target genes for additional study.MIF ͉ normalization ͉ signficance analysis ͉ SLIM A ffymetrix GeneChip arrays (1, 2) have been widely used for monitoring mRNA expression in many areas of biomedical research. The high-density oligonucleotide array technology allows researchers to monitor tens of thousands of genes in a single hybridization experiment as they are expressed differently in tissues and cells. The expression profile of an mRNA molecule of a gene is obtained by the combined intensity information from probes in a probe set, which consists of 11-20 probe pairs of oligonucleotides of 25 bp in length, interrogating a different part of the sequence of a gene. Several techniques have been proposed for extracting expression profiles from the information at probe level. These techniques include the detection signals that are prominently featured in Affymetrix Micorarray Suite 5.0 (MAS 5.0) software, the model-based expression index (3), and the robust multichip average (4, 5). A comprehensive review and comparisons of various expression measures are given in refs. 6 and 7.To account for the overall brightness of scanned images and other experimental variations such as differences in sample preparation and array production, normalization is needed for direct array-to-array comparisons. Several methods (7-10) have been proposed for normalizing data at probe level, and their impacts on the analysis of gene expressions have been examined. However, most researchers use detection signals from MAS 5.0 as starting points of their investigation. Yet, as reported below, the techniques for probe-level normalizati...

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Multiple Hypothesis Testing in Microarray Experiments

Cited by 897 publications

References 50 publications

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Low dose radiation response curves, networks and pathways in human lymphoblastoid cells exposed from 1 to 10cGy of acute gamma radiation

Statistical Analysis of DNA Microarray Data in Cancer Research

Removing intensity effects and identifying significant genes for Affymetrix arrays in macrophage migration inhibitory factor-suppressed neuroblastoma cells

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