A mixture model approach for the analysis of microarray gene expression data

Allison, David B.; Gadbury, Gary L.; Heo, Moonseong; Fernández, José R.; Lee, Cheol Koo; Prolla, Thomas A.; Weindruch, Richard

doi:10.1016/s0167-9473(01)00046-9

Cited by 309 publications

(284 citation statements)

References 24 publications

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“…A t test for genotype differences was conducted as part of a mixed linear model analysis for each gene (Wolfinger et al, 2001) yielding 10,767 P-values. As described by Allison et al (2002), a mixture of uniform and a b distribution was fit to the observed distribution of the 10,767 P-values obtained from the mixed linear model analysis. The estimated parameters from the fit of the mixture model were used to estimate the posterior probability of differential expression for each gene and to estimate the proportion of false positive results among all genes with P-values #0.01 and estimated fold change .…”

Section: Discussionmentioning

confidence: 99%

Isolation, Characterization, and Pericycle-Specific Transcriptome Analyses of the Novel Maize Lateral and Seminal Root Initiation Mutant rum1

Woll

Borsuk²,

Stransky³

et al. 2005

Plant Physiology

182

190

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The monogenic recessive maize (Zea mays) mutant rootless with undetectable meristems 1 (rum1) is deficient in the initiation of the embryonic seminal roots and the postembryonic lateral roots at the primary root. Lateral root initiation at the shoot-borne roots and development of the aerial parts of the mutant rum1 are not affected. The mutant rum1 displays severely reduced auxin transport in the primary root and a delayed gravitropic response. Exogenously applied auxin does not induce lateral roots in the primary root of rum1. Lateral roots are initiated in a specific cell type, the pericycle. Cell-type-specific transcriptome profiling of the primary root pericycle 64 h after germination, thus before lateral root initiation, via a combination of laser capture microdissection and subsequent microarray analyses of 12k maize microarray chips revealed 90 genes preferentially expressed in the wild-type pericycle and 73 genes preferentially expressed in the rum1 pericycle (fold change .2; P-value ,0.01; estimated false discovery rate of 13.8%). Among the 51 annotated genes predominately expressed in the wild-type pericycle, 19 genes are involved in signal transduction, transcription, and the cell cycle. This analysis defines an array of genes that is active before lateral root initiation and will contribute to the identification of checkpoints involved in lateral root formation downstream of rum1.

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Section: Discussionmentioning

confidence: 99%

Isolation, Characterization, and Pericycle-Specific Transcriptome Analyses of the Novel Maize Lateral and Seminal Root Initiation Mutant rum1

Woll

Borsuk²,

Stransky³

et al. 2005

Plant Physiology

182

190

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show abstract

“…The pp is the Bayesian probability that a gene with a frequentist P value less than or equal to that observed is a gene for which there is a real difference between groups in expression level. This procedure provides an omnibus test of whether there is any overall effect of treatment on gene expression levels, an estimate of the total number of genes that have their expression levels altered, and a model describing the distribution of effects on gene expression levels (27).…”

Section: Methodsmentioning

confidence: 99%

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

Lee

Allison

Brand

et al. 2002

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

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289

218

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To provide a global analysis of gene expression in the aging heart, we monitored the expression of 9,977 genes simultaneously in 5-and 30-month-old male B6C3F1 mice by using high-density oligonucleotide microarrays and several statistical techniques. Aging was associated with transcriptional alterations consistent with a metabolic shift from fatty acid to carbohydrate metabolism, increased expression of extracellular matrix genes, and reduced protein synthesis. Caloric restriction (CR) started at 14 months of age resulted in a 19% global inhibition of age-related changes in gene expression. Interestingly, CR also resulted in alterations in gene expression consistent with preserved fatty acid metabolism, reduced endogenous DNA damage, decreased innate immune activity, apoptosis modulation, and a marked cytoskeletal reorganization. These observations provide evidence that aging of the heart is associated with specific transcriptional alterations, and that CR initiated in middle age may retard heart aging by inducing a profound transcriptional reprogramming.W hen started either early in life or at middle age, caloric restriction (CR) increases average and maximum lifespan, and reduces the incidence and delays the onset of spontaneous cancers and several other age-related diseases (1). Additionally, CR reduces the age-associated increase in reactive oxygen species (ROS)-induced molecular damage (2-5). Previously, we have used high-density oligonucleotide arrays to define aging and CR-related transcriptional alterations in mouse skeletal muscle (6) and brain (7). These reports provided evidence for an age-associated stress response characterized by the induction of heat-shock factors and other oxidative stress-induced transcripts. CR prevented these age-related alterations completely or partially. Both studies provided further support for the concept that oxidative stress may be an important, and perhaps underlying cause of the aging process of postmitotic tissues.The cardiac myocyte is the most energy demanding cell in the body, contracting constantly, 3 billion times or more in the average human lifespan (8), requiring large supplies of high-energy phosphates (9). Age-related changes in human and rodent hearts include a reduction in the number of myocytes (10, 11), myocyte hypertrophy (11, 12), cardiac fibrosis (13), lipofuscin pigment accumulation (14), a reduction in calcium transport across sarcoplasmic reticulum membrane (15), and alterations in the response to ␤-adrenergic stimulation (16). Collectively, these alterations likely contribute to age-related heart diseases being the leading cause of mortality in the U.S. (17). CR reduces the severity of spontaneous cardiomyopathy in male Sprague-Dawley rats (18) and prevents age-associated alterations in late diastolic function in B6D2F 1 mice (19). At the molecular level, CR reduces the concentration of both 8-hydroxydeoxyguanosine in DNA (20) and dityrosine cross-linking of proteins (21) in the heart of aging mice, and prevents somatic mitochondrial genomic rear...

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“…The Bayesian posterior probability of being a false discovery (expressed as false discovery rate [FDR]) was estimated for each probe set individually, based on the Welch p values, using a mixture model described elsewhere [23,24]. We focused on the genes among those most differentially expressed that had corresponding probe sets with a less than 0.1% FDR, i.e.…”

Section: Data Analysesmentioning

confidence: 99%

Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes

et al. 2005

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Aims/hypothesis: Obesity increases the risk of developing major diseases such as diabetes and cardiovascular disease. Adipose tissue, particularly adipocytes, may play a major role in the development of obesity and its comorbidities. The aim of this study was to characterise, in adipocytes from obese people, the most differentially expressed genes that might be relevant to the development of obesity. Methods: We carried out microarray gene profiling of isolated abdominal subcutaneous adipocytes from 20 non-obese (BMI 25±3 kg/m 2 ) and 19 obese (BMI 55± 8 kg/m 2 ) non-diabetic Pima Indians using Affymetrix HG-U95 GeneChip arrays. After data analyses, we measured the transcript levels of selected genes based on their biological functions and chromosomal positions using quantitative real-time PCR. Results: The most differentially expressed genes in adipocytes of obese individuals consisted of 433 upregulated and 244 downregulated genes. Of these, 410 genes could be classified into 20 functional Gene Ontology categories. The analyses indicated that the inflammation/ immune response category was over-represented, and that most inflammation-related genes were upregulated in adipocytes of obese subjects. Quantitative real-time PCR confirmed the transcriptional upregulation of representative inflammation-related genes (CCL2 and CCL3) encoding the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein 1α. The differential expression levels of eight positional candidate genes, including inflammation-related THY1 and C1QTNF5, were also confirmed. These genes are located on chromosome 11q22-q24, a region with linkage to obesity in the Pima Indians. Conclusions/interpretation: This study provides evidence supporting the active role of mature adipocytes in obesityrelated inflammation. It also provides potential candidate genes for susceptibility to obesity.

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A mixture model approach for the analysis of microarray gene expression data

Cited by 309 publications

References 24 publications

Isolation, Characterization, and Pericycle-Specific Transcriptome Analyses of the Novel Maize Lateral and Seminal Root Initiation Mutant rum1

Isolation, Characterization, and Pericycle-Specific Transcriptome Analyses of the Novel Maize Lateral and Seminal Root Initiation Mutant rum1

Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts

Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes

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