One limitation of our method is that the functional link of some kinase/phosphatase cannot be predicted because they have no signature. In other words, the expression level of downstream genes do not change upon deletion of the corresponding regulator. One explanation of this phenomenon is the buffering effect. For example, Mkk1 and Mkk2 are two redundant MAPKKs involved in the protein kinase signaling pathway that controls cell integrity. The deletion of either kinase has no significant effect, since the other one will take over its entire function. Another reason is that some kinase are inactive in normal conditions. This limitation can be compensated by measuring the expression level under conditions of induced stress or by constructing double mutation strains in which functionally redundant kinase are deleted simultaneously. Our method will gain additional power when such **data** becomes available.