Figure 2.

Flow chart of the proposed method. (A) Left panel: Gene expression data from microarray studies and DNA-binding data (ChIP-chip) are used as input to the GRAM algorithm in order to identify gene modules and their regulators. Middle panel: Bibliographical information from public databases is used to add another layer of regulators and build the three-layer regulatory cascade. Right panel: ANNs with the same structure as the biological cascade are built and trained to predict the expression of the target gene given the expression of the upper-layer regulators. (B) The basic scheme was extended to include additional biological aspects such as time-delays among the expression of a transcription factor and the expression of the target gene and formation of heterodimers.