Distance correlation application to gene co-expression network analysis

To construct gene co-expression networks, it is necessary to evaluate the correlation between different gene expression profiles. However, commonly used correlation metrics, including both linear (such as Pearson's correlation) and monotonic (such as Spearman's correlation) dependence metrics, are not enough to observe the nature of real biological systems. Hence, introducing a more informative correlation metric when constructing gene co-expression networks is still an interesting topic.

In this paper, we test distance correlation, a correlation metric integrating both linear and non-linear dependence, with other three typical metrics (Pearson's correlation, Spearman's correlation, and maximal information coefficient) on four different arrays (macrophage and liver) and RNA-seq (cervical cancer and pancreatic cancer) datasets. Among all the metrics, distance correlation is distribution free and can provide better performance on complex relationships and anti-outlier. Furthermore, distance correlation is applied to Weighted Gene Co-expression Network Analysis (WGCNA) for constructing a gene co-expression network analysis method which we named Distance Correlation-based Weighted Gene Co-expression Network Analysis (DC-WGCNA). Compared with traditional WGCNA, DC-WGCNA can enhance the result of enrichment analysis and improve the module stability.

Distance correlation is better at revealing complex biological relationships between gene profiles compared with other correlation metrics, which contribute to more meaningful modules when analyzing gene co-expression networks. However, due to the high time complexity of distance correlation, the implementation requires more computer memory.