We now apply a statistical implementation of the Granger causality concept to map directionally specific causal influences between pairs of recorded features. Thus we begin to define a wiring pattern for the unperturbed cell migration system. Subsequently, we employ well-characterized perturbations to reveal plasticity in this wiring pattern. This is a fundamentally important finding because it demonstrates that the perturbations frequently used to illuminate wiring Tulathromycin B patterns may, in some cases, partially distort our view of such information processing structures. We therefore propose that, for the purpose of mapping information flow in Sibutramine HCl complex cellular systems, perturbationindependent strategies such as that described herein may provide a valuable complement to existing perturbation-dependent approaches. A variety of studies have previously described correlations between organizational and behavioral features of cell migration, yet the orientation of cause and effect in these relationships has remained undefined. We now extend on such correlative analyses by describing a novel strategy for directionally specific mapping of information flow in the form of causal influence. A key differentiating aspect of our approach is the focus on charting causal influences based on sensitivity to the natural heterogeneity that arises within individual experimental conditions, as opposed to relying on perturbation-induced differences between conditions. This permits: a) the delineation of causal influence patterns on a per condition basis, which in turn facilitates; b) the comparison of these wiring patterns between alternatively perturbed conditions. Through these capabilities we now provide proof-of-principle for plasticity and contextual-dependence in the regulatory wiring of the cell migration system, while also delineating specific, functionally significant relationships between key features within this system. The plasticity of causal wiring in the cell migration system is illuminated by differences observed in pair-wise causal influences under control and Rho-activated conditions. Specifically, this plasticity is evidenced by the disruption of two causal interactions within the causality chain defined in control cells, and is positively exemplified by alterations to the causal interaction detected between cell speed and cell compactness. The nature and implications of these specific alterations are discussed further below. In general, however, these perturbation-induced differences in inter-feature connectivity provide proof-of-principle as to the flexibility and adaptability of the causal wiring pattern governing cell migration. Concomitantly, the equivalence between the causality chains revealed in control and ROCK-inhibited cells strongly support the validity and relevance of the defined causal interactions. Thus, in combination, these unique findings demonstrate both robustness and contextually dependent plasticity in the functional relationships between coarse-grained features at the core of the cell migration system. These findings hold the important implication that although some causal regulatory influences may be conserved even under strongly altered conditions, a singular characterization of inter-feature relations is unlikely to be generalizable. This notion seems likely to also be important for the molecular-scale networks and components that underpin the coarse-grained 
macromolecular features assessed herein.