CODC: a Copula-based model to identify differential coexpression

Abstract

AbstractDifferential coexpression has recently emerged as a new way to establish a fundamental difference in expression pattern among a group of genes between two populations. Earlier methods used some scoring techniques to detect changes in correlation patterns of a gene pair in two conditions. However, modeling differential coexpression by means of finding differences in the dependence structure of the gene pair has hitherto not been carried out. We exploit a copula-based framework to model differential coexpression between gene pairs in two different conditions. The Copula is used to model the dependency between expression profiles of a gene pair. For a gene pair, the distance between two joint distributions produced by copula is served as differential coexpression. We used five pan-cancer TCGA RNA-Seq data to evaluate the model that outperforms the existing state of the art. Moreover, the proposed model can detect a mild change in the coexpression pattern across two conditions. For noisy expression data, the proposed method performs well because of the popular scale-invariant property of copula. In addition, we have identified differentially coexpressed modules by applying hierarchical clustering on the distance matrix. The identified modules are analyzed through Gene Ontology terms and KEGG pathway enrichment analysis.