In addition, the identification of response clusters, within which the responses might be considered continuous, enables the use of traditional response surface approximation for optimization.
Therefore, the Fzf1p response clusters were not separated into early and late response clusters as in the initial model.
Five major gene clusters were identified using correlation cutoff 0.75 with subsequent manual adjustment: Fzf1p early response, Fzf1p late response, ESR, oxidative phosphorylation, and galactose response clusters (Table 1).
The core structure of the Fzf1p-dependent NO·-specific response sub-network (nitric oxide, FZF1 genotype Fzf1p activity, and Fzf1p response clusters) was predicted and maintained throughout the three models.
Previously, Ramsey, et al. (2008) [27] analyzed a macrophage compendium (also used as part of the present study) using a variety of approaches and described two 'core early response' clusters that overlap with our module significantly (∼50% shared genes).
The core NO· specific response (Fzf1p early and late response clusters), unlike other transcriptional responses, was controlled through the activation of the transcription factor Fzf1p. NO· also triggered a general environmental stress response, which was shared by exposing to oxidative agents.
