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Approaches in Gene Coexpression Analysis in Eukaryotes

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Genes whose expression levels rise and fall similarly in a large set of samples, may be considered coexpressed. Gene coexpression analysis refers to the en masse discovery of coexpressed genes from a large variety of transcriptomic experiments. The type of biological networks that studies gene coexpression, known as Gene Coexpression Networks, consist of an undirected graph depicting genes and their coexpression relationships. Coexpressed genes are clustered in smaller subnetworks, the predominant biological roles of which can be determined through enrichment analysis. By studying well-annotated gene partners, the attribution of new roles to genes of unknown function or assumption for participation in common metabolic pathways can be achieved, through a guilt-by-association approach. In this review, we present key issues in gene coexpression analysis, as well as the most popular tools that perform it.

Abstract

Gene coexpression analysis constitutes a widely used practice for gene partner identification and gene function prediction, consisting of many intricate procedures. The analysis begins with the collection of primary transcriptomic data and their preprocessing, continues with the calculation of the similarity between genes based on their expression values in the selected sample dataset and results in the construction and visualisation of a gene coexpression network (GCN) and its evaluation using biological term enrichment analysis. As gene coexpression analysis has been studied extensively, we present most parts of the methodology in a clear manner and the reasoning behind the selection of some of the techniques. In this review, we offer a comprehensive and comprehensible account of the steps required for performing a complete gene coexpression analysis in eukaryotic organisms. We comment on the use of RNA-Seq vs. microarrays, as well as the best practices for GCN construction. Furthermore, we recount the most popular webtools and standalone applications performing gene coexpression analysis, with details on their methods, features and outputs.

SUBMITTER: Zogopoulos V

PROVIDER: S-EPMC9312353 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:THE MERGING OF NETWORK THEORY AND MICROARRAY DATA ANALYSIS TECHNIQUES HAS SPAWNED A NEW FIELD: gene coexpression network analysis. While network methods are increasingly used in biology, the network vocabulary of computational biologists tends to be far more limited than that of, say, social network theorists. Here we review and propose several potentially useful network concepts. We take advantage of the relationship between network theory and the field of microarray data analysis to clarify the meaning of and the relationship among network concepts in gene coexpression networks. Network theory offers a wealth of intuitive concepts for describing the pairwise relationships among genes, which are depicted in cluster trees and heat maps. Conversely, microarray data analysis techniques (singular value decomposition, tests of differential expression) can also be used to address difficult problems in network theory. We describe conditions when a close relationship exists between network analysis and microarray data analysis techniques, and provide a rough dictionary for translating between the two fields. Using the angular interpretation of correlations, we provide a geometric interpretation of network theoretic concepts and derive unexpected relationships among them. We use the singular value decomposition of module expression data to characterize approximately factorizable gene coexpression networks, i.e., adjacency matrices that factor into node specific contributions. High and low level views of coexpression networks allow us to study the relationships among modules and among module genes, respectively. We characterize coexpression networks where hub genes are significant with respect to a microarray sample trait and show that the network concept of intramodular connectivity can be interpreted as a fuzzy measure of module membership. We illustrate our results using human, mouse, and yeast microarray gene expression data. The unification of coexpression network methods with traditional data mining methods can inform the application and development of systems biologic methods.

Dataset Information

Approaches in Gene Coexpression Analysis in Eukaryotes

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