Figure 1

Illustration of multi-modulator gene regulation and the CoMRe method. (A) Illustration of multi-modulator gene regulation. From the point of view of regulation under modulation, regulation strength (left right arrow) between a pair of genes can be modulated by (i.e ., dependent on) expression levels of some modulator genes. In the multi-modulator model, the modulator genes can have cooperative (or uncooperative) effects with differential capability (β values) in determining strength of gene-gene regulation. (B) Analysis flowchart of CoMRe. CoMRe is designed to infer the relationship between multiple modulator genes and modulated gene regulation from high-throughput datasets. Mathematically, CoMRe is composed of a multiple regression model that takes expression levels of the modulator genes as inputs and regulation strength between genes (measured by covariability) as output. Circled zin the figure stands for z-transform. Mathematical details are described in the Methods section.