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- Gusnanto, A, et al.
(författare)
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Fold-change estimation of differentially expressed genes using mixture mixed-model
- 2005
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Ingår i: Statistical applications in genetics and molecular biology. - : Walter de Gruyter GmbH. - 1544-6115 .- 2194-6302. ; 4, s. Article26-
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Tidskriftsartikel (refereegranskat)abstract
- Microarray experiments produce expression measurements for thousands of genes simultaneously, though usually for a small number of RNA samples. The most common problem is the identification of genes that are differentially expressed between different groups of samples or biological conditions. As the number of genes far exceeds the number of RNA samples, the inherent multiplicity poses a severe problem in both hypothesis testing and effect estimation. While much of the recent literature is focused on the hypothesis aspects, we concentrate in this paper on effect estimation as a tool for the identification of differentially expressed genes. We propose a linear mixed model where the random effects are assumed to follow a mixture distribution, and study in detail the case of three normals, corresponding to genes that are down-, up- or non regulated. Our approach leads to a new type of non-linear shrinkage estimation, where a proportion of estimates is shrunk to zero, while the rest follows standard linear shrinkage. This allows us to estimate the log fold-change of the genes involved and to identify those that are differentially expressed within the same model framework. We investigate the operating characteristics of our method using simulation and spike-in studies, and illustrate its application to real data using a breast-cancer dataset.
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- Xue, Yongtao, et al.
(författare)
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A DNA microarray for fission yeast : minimal changes in global gene expression after temperature shift
- 2004
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Ingår i: Yeast. - : Wiley. - 0749-503X .- 1097-0061. ; 21:1, s. 25-39
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Tidskriftsartikel (refereegranskat)abstract
- Completion of the fission yeast genome sequence has opened up possibilities for post-genomic approaches. We have constructed a DNA microarray for genome-wide gene expression analysis in fission yeast. The microarray contains DNA fragments, PCR-amplified from a genomic DNA template, that represent >99% of the 5000 or so annotated fission yeast genes, as well as a number of control sequences. The GenomePRIDE software used attempts to design similarly sized DNA fragments corresponding to gene regions within single exons, near the 3'-end of genes that lack homology to other fission yeast genes. To validate the design and utility of the array, we studied expression changes after a 2 h temperature shift from 25degreesC to 36degreesC, conditions widely used when studying temperature-sensitive mutants. Obligingly, the vast majority of genes do not change more than two-fold, supporting the widely held view that temperature-shift experiments specifically reveal phenotypes associated with temperature-sensitive mutants. However, we did identify a small group of genes that showed a reproducible change in expression. Importantly, most of these corresponded to previously characterized heat-shock genes, whose expression has been reported to change after more extreme temperature shifts than those used here.. We conclude that the DNA microarray represents a useful resource for fission yeast researchers as well as the broader yeast community, since it will facilitate comparison with the distantly related budding yeast, Saccharomyces cerevisiae. To maximize the utility of this resource, the array and its component parts are fully described in On-line Supplementary Information and are also available commercially.
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