Figure 3. Response rules to modify signaling topologies when the first molecule is perturbed.

(A) Analyzing time to activation: Rule 1, Time delay and Rule 2, Rapid bypass, (B) Analyzing peak activation levels: Rule 3, Missing flux, Rule 4, Signaling Flux Redistribution (SFR), Rule 5, Lack of SFR and Rule 6, Dominant and Recessive flux, (C) Analyzing activation patterns: Rule 7, Reversible flux, Rule 8, Superposing flux, Rule 9, Continuous flux, and Rule 10, Oscillations. See maintext for descriptions. Note that rules 1–6 are developed from first-order response and the law of signaling flux conservation in pulse perturbation. Rules 7–10 are introduced to interpret any non-linear response or those that do not obey the law of conservation. These rules are not exhaustive and can possibly be further categorized if detailed experimental data for each molecule is available. The rules serve as guide to modify the overt topology highlighting the key missing features only.