New Statistical Methods for Constructing Robust Differential Correlation Networks to characterize the interactions among microRNAs

The interplay among microRNAs (miRNAs) plays an important role in the developments of complex human diseases. Co-expression networks can characterize the interactions among miRNAs. Differential correlation network is a powerful tool to investigate the differences of co-expression networks between cases and controls. To construct a differential correlation network, the Fisher’s Z-transformation test is usually used. However, the Fisher’s Z-transformation test requires the normality assumption, the violation of which would result in inflated Type I error rate. Several bootstrapping-based improvements for Fisher’s Z test have been proposed. However, these methods are too computationally intensive to be used to construct differential correlation networks for high-throughput genomic data. In this article, we proposed six novel robust equal-correlation tests that are computationally efficient. The systematic simulation studies and a real microRNA data analysis showed that one of the six proposed tests (ST5) overall performed better than other methods.