Computational Analysis of Sexual Dimorphism in Gene Expression Under Toxico-Pathological States

Abstract

This thesis presents a study using toxicogenomic approaches to investigate genes that show sex-dimorphic expression under toxico-pathological states in the zebrafish liver and several human tissues. For zebrafish, the analysis revealed that many functionally diverse metabolic genes were sex-dimorphic in their response to chemical treatments, which were enriched in pathways belonging to xenobiotic, lipid, and nucleotide metabolism. The temporal differences of the sex-dimorphic responses were observed which suggested that both genes and pathways are differently correlated during different periods of chemical perturbation. Subsequently, the analysis from both zebrafish and human revealed obvious inverted expression profiles of sex-biased genes, where affected males tended to up-regulate genes of female-biased expression and down-regulate genes of male-biased expression, and vice versa in affected females. Intriguingly, the extent of these inverted profiles correlated well to the severity of toxico-pathological states. The ubiquity of sex-dimorphic activities indicates the importance of considering the sex factor biological researches.