Identification of common coexpression modules based on quantitative network comparison

Abstract

Background: Finding common molecular interactions from different samples is essential work to understanding diseases and other biological processes. Coexpression networks and their modules directly reflect sample-specific interactions among genes. Therefore, identification of common coexpression network or modules may reveal the molecular mechanism of complex disease or the relationship between biological processes. However, there has been no quantitative network comparison method for coexpression networks and we examined previous methods for other networks that cannot be applied to coexpression network. Therefore, we aimed to propose quantitative comparison methods for coexpression networks and to find common biological mechanisms between Huntington's disease and brain aging by the new method. Results: We proposed two similarity measures for quantitative comparison of coexpression networks. Then, we performed experiments using known coexpression networks. We showed the validity of two measures and evaluated threshold values for similar coexpression network pairs from experiments. Using these similarity measures and thresholds, we quantitatively measured the similarity between disease-specific and aging-related coexpression modules and found similar Huntington's disease-aging coexpression module pairs. Conclusions: We identified similar Huntington's disease-aging coexpression module pairs and found that these modules are related to brain development, cell death, and immune response. It suggests that up-regulated cell signalling related cell death and immune/inflammation response may be the common molecular mechanisms in the pathophysiology of HD and normal brain aging in the frontal cortex.