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      DiffCoEx: a simple and sensitive method to find differentially coexpressed gene modules

      research-article
      1 ,   1 , 2 , 1 , 3 ,
      BMC Bioinformatics
      BioMed Central

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          Abstract

          Background

          Large microarray datasets have enabled gene regulation to be studied through coexpression analysis. While numerous methods have been developed for identifying differentially expressed genes between two conditions, the field of differential coexpression analysis is still relatively new. More specifically, there is so far no sensitive and untargeted method to identify gene modules (also known as gene sets or clusters) that are differentially coexpressed between two conditions. Here, sensitive and untargeted means that the method should be able to construct de novo modules by grouping genes based on shared, but subtle, differential correlation patterns.

          Results

          We present DiffCoEx, a novel method for identifying correlation pattern changes, which builds on the commonly used Weighted Gene Coexpression Network Analysis (WGCNA) framework for coexpression analysis. We demonstrate its usefulness by identifying biologically relevant, differentially coexpressed modules in a rat cancer dataset.

          Conclusions

          DiffCoEx is a simple and sensitive method to identify gene coexpression differences between multiple conditions.

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          Most cited references12

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          Hierarchical organization of modularity in metabolic networks

          Spatially or chemically isolated functional modules composed of several cellular components and carrying discrete functions are considered fundamental building blocks of cellular organization, but their presence in highly integrated biochemical networks lacks quantitative support. Here we show that the metabolic networks of 43 distinct organisms are organized into many small, highly connected topologic modules that combine in a hierarchical manner into larger, less cohesive units, their number and degree of clustering following a power law. Within Escherichia coli the uncovered hierarchical modularity closely overlaps with known metabolic functions. The identified network architecture may be generic to system-level cellular organization.
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            Molecular networks as sensors and drivers of common human diseases.

            The molecular biology revolution led to an intense focus on the study of interactions between DNA, RNA and protein biosynthesis in order to develop a more comprehensive understanding of the cell. One consequence of this focus was a reduced attention to whole-system physiology, making it difficult to link molecular biology to clinical medicine. Equipped with the tools emerging from the genomics revolution, we are now in a position to link molecular states to physiological ones through the reverse engineering of molecular networks that sense DNA and environmental perturbations and, as a result, drive variations in physiological states associated with disease.
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              Differential coexpression analysis using microarray data and its application to human cancer.

              Microarrays have been used to identify differential expression of individual genes or cluster genes that are coexpressed over various conditions. However, alteration in coexpression relationships has not been studied. Here we introduce a model for finding differential coexpression from microarrays and test its biological validity with respect to cancer. We collected 10 published gene expression datasets from cancers of 13 different tissues and constructed 2 distinct coexpression networks: a tumor network and normal network. Comparison of the two networks showed that cancer affected many coexpression relationships. Functional changes such as alteration in energy metabolism, promotion of cell growth and enhanced immune activity were accompanied with coexpression changes. Coregulation of collagen genes that may control invasion and metastatic spread of tumor cells was also found. Cluster analysis in the tumor network identified groups of highly interconnected genes related to ribosomal protein synthesis, the cell cycle and antigen presentation. Metallothionein expression was also found to be clustered, which may play a role in apoptosis control in tumor cells. Our results show that this model would serve as a novel method for analyzing microarrays beyond the specific implications for cancer.
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                Author and article information

                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central
                1471-2105
                2010
                6 October 2010
                : 11
                : 497
                Affiliations
                [1 ]Groningen Bioinformatics Center, University of Groningen, Kerklaan 30, 9751 NN Haren, the Netherlands
                [2 ]Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK
                [3 ]Department of Genetics, University Medical Center Groningen, 9700 RB, Groningen, the Netherlands
                Article
                1471-2105-11-497
                10.1186/1471-2105-11-497
                2976757
                20925918
                6b44553a-1bd2-4baf-b028-73162c9e1670
                Copyright ©2010 Tesson et al; 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
                : 2 June 2010
                : 6 October 2010
                Categories
                Methodology Article

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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