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      Regulon organization of Arabidopsis

      research-article
      1 , , 2 ,
      BMC Plant Biology
      BioMed Central

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          Abstract

          Background

          Despite the mounting research on Arabidopsis transcriptome and the powerful tools to explore biology of this model plant, the organization of expression of Arabidopsis genome is only partially understood. Here, we create a coexpression network from a 22,746 Affymetrix probes dataset derived from 963 microarray chips that query the transcriptome in response to a wide variety of environmentally, genetically, and developmentally induced perturbations.

          Results

          Markov chain graph clustering of the coexpression network delineates 998 regulons ranging from one to 1623 genes in size. To assess the significance of the clustering results, the statistical over-representation of GO terms is averaged over this set of regulons and compared to the analogous values for 100 randomly-generated sets of clusters. The set of regulons derived from the experimental data scores significantly better than any of the randomly-generated sets. Most regulons correspond to identifiable biological processes and include a combination of genes encoding related developmental, metabolic pathway, and regulatory functions. In addition, nearly 3000 genes of unknown molecular function or process are assigned to a regulon. Only five regulons contain plastomic genes; four of these are exclusively plastomic. In contrast, expression of the mitochondrial genome is highly integrated with that of nuclear genes; each of the seven regulons containing mitochondrial genes also incorporates nuclear genes. The network of regulons reveals a higher-level organization, with dense local neighborhoods articulated for photosynthetic function, genetic information processing, and stress response.

          Conclusion

          This analysis creates a framework for generation of experimentally testable hypotheses, gives insight into the concerted functions of Arabidopsis at the transcript level, and provides a test bed for comparative systems analysis.

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          Most cited references94

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          Cluster analysis and display of genome-wide expression patterns.

          A system of cluster analysis for genome-wide expression data from DNA microarray hybridization is described that uses standard statistical algorithms to arrange genes according to similarity in pattern of gene expression. The output is displayed graphically, conveying the clustering and the underlying expression data simultaneously in a form intuitive for biologists. We have found in the budding yeast Saccharomyces cerevisiae that clustering gene expression data groups together efficiently genes of known similar function, and we find a similar tendency in human data. Thus patterns seen in genome-wide expression experiments can be interpreted as indications of the status of cellular processes. Also, coexpression of genes of known function with poorly characterized or novel genes may provide a simple means of gaining leads to the functions of many genes for which information is not available currently.
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            A gene-coexpression network for global discovery of conserved genetic modules.

            To elucidate gene function on a global scale, we identified pairs of genes that are coexpressed over 3182 DNA microarrays from humans, flies, worms, and yeast. We found 22,163 such coexpression relationships, each of which has been conserved across evolution. This conservation implies that the coexpression of these gene pairs confers a selective advantage and therefore that these genes are functionally related. Many of these relationships provide strong evidence for the involvement of new genes in core biological functions such as the cell cycle, secretion, and protein expression. We experimentally confirmed the predictions implied by some of these links and identified cell proliferation functions for several genes. By assembling these links into a gene-coexpression network, we found several components that were animal-specific as well as interrelationships between newly evolved and ancient modules.
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              Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation.

              Y. H. Yang (2002)
              There are many sources of systematic variation in cDNA microarray experiments which affect the measured gene expression levels (e.g. differences in labeling efficiency between the two fluorescent dyes). The term normalization refers to the process of removing such variation. A constant adjustment is often used to force the distribution of the intensity log ratios to have a median of zero for each slide. However, such global normalization approaches are not adequate in situations where dye biases can depend on spot overall intensity and/or spatial location within the array. This article proposes normalization methods that are based on robust local regression and account for intensity and spatial dependence in dye biases for different types of cDNA microarray experiments. The selection of appropriate controls for normalization is discussed and a novel set of controls (microarray sample pool, MSP) is introduced to aid in intensity-dependent normalization. Lastly, to allow for comparisons of expression levels across slides, a robust method based on maximum likelihood estimation is proposed to adjust for scale differences among slides.
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                Author and article information

                Journal
                BMC Plant Biol
                BMC Plant Biology
                BioMed Central
                1471-2229
                2008
                30 September 2008
                : 8
                : 99
                Affiliations
                [1 ]CRS4 Bioinformatics Laboratory, Parco Scientifico e Technologico POLARIS, 09010 Pula (CA), Italy
                [2 ]Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011, USA
                Article
                1471-2229-8-99
                10.1186/1471-2229-8-99
                2567982
                18826618
                a201bcc2-f890-464f-bac0-4c9d4842a893
                Copyright © 2008 Mentzen and Wurtele; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 June 2008
                : 30 September 2008
                Categories
                Research Article

                Plant science & Botany
                Plant science & Botany

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