Overview of the workflow inside Mod_MPGE. Relying on three inputs (miR2gene, TF2gene, and an MPGE dataset), Mod_MPGE performs a one-sided Kolmogorov-Smirnov (K-S) test to evaluate the significance of miRNA degradating ability in human cells, a non-parametric statistical test to refine miRNA's degraded targets from forward-predicted putative targets, a pre-filtering uni-variate linear regression model to cut down the regulator numbers and an ultimate multi-variate stepwise linear regression model to determine miRNA's downstream TF mediators. Taking the sifted miRNA→gene and TF→gene regulations together, a hypothetical two-layer regulatory network centered on the perturbed miRNA and its downstream mediating TFs is mapped. In the formulae, E
stands for the mRNA level of a target gene g; b
, with values zero or one, encode the putative regulatory relationships between g and miRNA m, and g and TF
, respectively; a
quantifies the purturbed miRNA's and a TF's regulating coefficients (regulatory strength), which are to be determined through the linear regression modelling.